Supplementary Information
Structural Capacitance in Protein Evolution and Human Diseases
Chen Li, Liah V T Clark, Rory Zhang, Benjamin T Porebski, Julia M. McCoey, Natalie A. Borg, Geoffrey I. Webb, Itamar Kass, Malcolm Buckle, Jiangning Song, Adrian Woolfson, and Ashley M. Buckle
Supplementary tables
Table S1. Disorder prediction using the human disease and polymorphisms dataseta
OR DR OO OD DD DO mutations mutations 24,758 650 2,741 513 Disease 25,408 3,254 97.44% 2.56% 84.23% 15.77% 26,559 809 11,135 1,218 Non-disease 27,368 12,353 97.04% 2.96% 90.14% 9.86%
ahttp://www.uniprot.org/docs/humsavar [1] (see Materials and Methdos). The numbers listed are the ones of unique mutations. ‘Unclassifiied’ mutations, according to the UniProt, were not counted. O = predicted as ordered; OR = Ordered regions D = predicted as disordered; DR = Disordered regions
1 Table S2. Mutations in long disordered regions (LDRs) of human proteins predicted to produce a DO transitiona
Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf UHRF1-binding protein 1- A0JNW5/rs7296162 like S1147L - 4 2^ 101 6 3 A4D1E1/rs801841 Zinc finger protein 804B V1195I - 3* 2^ 37 6 1 A6NJV1/rs2272466 UPF0573 protein C2orf70 Q177L - 2* 4 34 3 1 Golgin subfamily A member A7E2F4/rs347880 8A K480N - 2* 2^ 91 N/A 2 Axonemal dynein light O14645/rs11749 intermediate polypeptide 1 A65V - 3* 3 43 N/A 2 Centrosomal protein of 290 O15078/rs374852145 kDa R2210C - 2 3 123 5 1 Fanconi anemia group G O15287/rs4986939 protein S378L - 2 2^ 35 5 1 Centriolar coiled-coil protein O43303/rs3751821 of 110 kDa P171L - 4 2^ 39 7 2 O43734/rs13190932 Adapter protein CIKS R83W - 2* 3^ 189 5 2 O60240/rs6496589 Perilipin-1 P194A - 3* 2^ 32 8 1 G protein-regulated inducer O60269/rs4445576 of neurite outgrowth 2 S328C - 2* 2^ 31 6 1 Nucleolar pre-ribosomal- O60287/rs762225 associated protein 1 P2071R - 2 3^ 53 6 1 Epilepsy; familial focal; GATOR complex protein with variable foci 1 O75140/rs202226316 DEPDC5 A452V (FFEVF1) [MIM:604364] 2* 2^ 31 N/A 1 O75161/rs17472401 Nephrocystin-4 R848W - 3* 2^ 45 6 1 O75161/rs571655 Nephrocystin-4 E618K - 3* 2^ 30 7 1 Calcium-binding tyrosine phosphorylation-regulated O75952/rs3786417 protein T74M - 2* 2^ 113 5 2 P07498/rs1048152 Kappa-casein R110L - 3* 2^ 35 N/A 1
2 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Polycystic kidney disease; autosomal recessive P08F94/rs146680689 Fibrocystin R3957C (ARPKD) [MIM:263200] 3* 4 40 N/A 1 P10909/rs9331936 Clusterin N317H - 2 2^ 48 4 1 P15502/rs17855988 Elastin G610R - 2 2^ 385 N/A 1 P28290/rs13419020 Sperm-specific antigen 2 R833W - 3 2^ 224 5 2 P28290/rs17647806 Sperm-specific antigen 2 P836L - 4 2^ 169 7 2 P41440/rs35786590 Folate transporter 1 A558V - 3 2^ 51 8 1 P55327/rs35099105 Tumor protein D52 D52Y - 3* 2^ 55 8 2 Down syndrome critical P59020/rs13864 region protein 9 R76L - 3* 3 31 N/A 1 Uncharacterized protein Q0P670/rs13290 SPEM2 S108A - 2 2^ 67 4 1 Fanconi anemia core complex-associated protein Q0VG06/rs11552304 100 P660L - 2 2^ 55 N/A 1 Chromatin assembly factor 1 Q13111/rs35651457 subunit A D167V - 2 3 84 5 2 Ventricular zone-expressed PH domain-containing Q14D04/rs59504298 protein homolog 1 S501L - 3* 2^ 68 8 2 Pericentriolar material 1 Q15154/rs370429 protein T1543I - 2 4 41 N/A 1 TATA box-binding protein- associated factor RNA Q15572/rs4150167 polymerase I subunit C G523R - 2 2^ 41 5 1 Q15884/rs35386391 Protein FAM189A2 T233I - 3* 3 82 N/A 3 Uncharacterized protein Q17RF5/rs2306175 C4orf26 P30L - 3* 3 50 8 2 Neuroblastoma breakpoint Q3BBV0/rs11581926 family member 1 Q850K - 2* 3^ 131 N/A 1
3 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Microtubule-associated Q49MG5/rs2305050 protein 9 N601D - 2* 2^ 104 8 1 Keratin-associated protein 13- Q52LG2/rs16986753 2 R26C - 2 2^ 88 1 1 Putative uncharacterized protein encoded by Q52M75/rs17366761 LINC01554 R85C - 2 2^ 42 5 1 Coiled-coil domain- Q53HC0/rs11057401 containing protein 92 S70C - 2* 3 159 6 1 Q562F6/rs1036533 Shugoshin 2 G9D - 2 2^ 55 3 1 Coiled-coil domain- Q569K6/rs12167903 containing protein 157 P191L - 2* 3 41 5 1 Q5JSZ5/rs10736851 Protein PRRC2B S1630T - 2* 3 183 8 2 Uncharacterized protein Q5SNV9/rs6697244 C1orf167 S848I - 3 2^ 30 N/A 1 Q5SQ13/rs11787585 Proline-rich protein 31 L8F - 2* 2^ 150 6 2 Synaptosomal-associated Q5SQN1/rs17851681 protein 47 R381C - 4 2^ 42 5 1 Uncharacterized protein Q5SRN2/rs1003878 C6orf10 P161L - 2* 2^ 57 5 2 Uncharacterized protein Q5SRN2/rs1033500 C6orf10 P128L - 2* 2^ 52 6 1 Q5T1N1/rs9440631 Protein AKNAD1 H255Y - 2* 3 193 3 2 Vacuolar protein sorting- Q5THJ4/rs958068 associated protein 13D S1707F - 2 2^ 67 6 1 Q5VWN6/rs56856085 Protein FAM208B S724Y - 4 2^ 144 7 3 Muscular LMNA-interacting Q5VWP3/rs2275769 protein P376S - 2* 2^ 163 4 1 Uncharacterized protein Q5VXU9/rs7470491 C9orf84 H416R - 2 2^ 86 4 1 Uncharacterized protein Q5VYM1/rs10117097 C9orf131 L285F - 2* 2^ 256 6 1
4 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Q5W0A0/rs3014939 Glutamate-rich protein 6B E178K - 2* 2^ 177 6 1 Q5W0A0/rs749071 Glutamate-rich protein 6B T427I - 2* 3 45 4 2 Q6L8H2/rs7113784 Keratin-associated protein 5-3 S83C - 2 2^ 122 5 1 Q6PJF5/rs11553545 Inactive rhomboid protein 2 D528Y - 2* 4 48 5 1 Tylosis with esophageal cancer (TOC) Q6PJF5/rs387907130 Inactive rhomboid protein 2 P189L [MIM:148500] 3* 3 109 6 2 Q6PJW8/rs12075111 Consortin R399C - 3* 2^ 129 7 2 Coiled-coil domain- Q6PK04/rs11150805 containing protein 137 R177W - 3* 3 125 9 3 Q6ZP01/rs13393001 RNA-binding protein 44 D51H - 2* 2^ 72 N/A 1 Retrotransposon Gag-like Q6ZR62/rs7474140 protein 4 D162Y - 2* 2^ 100 4 1 Uncharacterized protein Q6ZU52/rs2236026 KIAA0408 S331L - 2 2^ 134 3 1 Spermatogenesis-associated Q6ZUB1/rs34791830 protein 31E1 A736V - 4 2^ 133 8 3 Pre-eclampsia/eclampsia 4 Q6ZVD7/rs41278532 Storkhead-box protein 1 N825I (PEE4) [MIM:609404] 2 2^ 83 5 1 Xin actin-binding repeat- Q702N8/rs60540208 containing protein 1 R695C - 2* 3 88 5 1 Xin actin-binding repeat- Q702N8/rs9823779 containing protein 1 R776W - 3* 2^ 38 6 3 Uncharacterized protein Q711Q0/rs56206226 C10orf71 R320L - 2* 2^ 440 6 2 Phospholipid phosphatase- Q7Z2D5/rs35285687 related protein type 4 A32V - 2* 2^ 41 6 1 Q7Z2Z1/rs3743372 Treslin R1885C - 2* 2^ 551 6 1 Q7Z3Z2/rs34049451 Protein RD3 R47C - 2* 2^ 32 6 1 Transmembrane channel-like Q7Z402/rs17854512 protein 7 R59W - 3* 2^ 49 8 1
5 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Transmembrane channel-like Q7Z403/rs34712518 protein 6 G191D - 2 2^ 40 6 1 Q7Z570/rs12105159 Zinc finger protein 804A G1152R - 2 2^ 77 4 1 Q7Z570/rs12476147 Zinc finger protein 804A Q261L - 2 2^ 58 4 1 Uncharacterized protein Q7Z7L8/rs12796667 C11orf96 R144C - 2* 3 155 5 2 Uncharacterized protein Q86TY3/rs3829765 C14orf37 T96I - 3* 2^ 75 6 3 Q86V40/rs1649292 Metalloprotease TIKI1 P430L - 2 2^ 57 6 1 Glycosylphosphatidylinositol -anchored high density Q8IV16/rs587777636 lipoprotein-binding protein 1 G56R - 2 2^ 48 6 1 Glycosylphosphatidylinositol -anchored high density Hyperlipoproteinemia 1D Q8IV16/rs78367243 lipoprotein-binding protein 1 S144F (HLPP1D) [MIM:615947] 3* 4 38 8 1 Bardet-Biedl syndrome 7 Bardet-Biedl syndrome 7 Q8IWZ6/rs119466001 protein H323R (BBS7) [MIM:615984] 2* 2^ 38 5 1 Q8IXS0/rs10485172 Protein FAM217A M442V - 2 2^ 91 4 1 Coiled-coil domain- Q8IYE0/rs1109968 containing protein 146 N345S - 2* 2^ 213 6 1 Coiled-coil domain- Q8IYE1/rs17853515 containing protein 13 E375V - 2* 2^ 92 5 1 Coiled-coil domain- Q8IYT3/rs55868409 containing protein 170 E345K - 2* 2^ 99 4 1 Coiled-coil domain- Q8IYX3/rs861854 containing protein 116 R96C - 2 3 136 N/A 2 Q8IZ63/rs3745640 Proline-rich protein 22 P118L - 2* 3 116 5 1 Q8N1H7/rs1033734 Protein SIX6OS1 S309L - 2* 2^ 198 6 1 Q8N205/rs34818970 Nesprin-4 S224L - 3* 2^ 74 7 3 Q8N2C7/rs35822936 Protein unc-80 homolog R131W - 2* 3^ 48 6 2 Hypotonia; infantile; with Q8N2C7/rs869025316 Protein unc-80 homolog P1700S psychomotor retardation 2* 2^ 80 3 1
6 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf and characteristic facies 2 (IHPRF2) [MIM:616801] Q8N307/rs11923495 Mucin-20 R666W - 2 4 163 3 2 Q8N307/rs3762739 Mucin-20 S671C - 2* 4 163 4 2 Q8N387/rs15783 Mucin-15 T202I - 3* 3 37 4 1 Usher syndrome type-1C Q8N6Y0/rs9676419 protein-binding protein 1 M439V - 2* 2^ 172 5 1 Coiled-coil domain- Q8N715/rs17852896 containing protein 185 R380L - 2* 3 244 5 2 Q8N7R1/rs1689291 POM121-like protein 12 G188E - 2 2^ 57 4 1 Putative uncharacterized protein encoded by Q8N8I6/rs2048058 LINC00482 R119C - 3* 3 85 6 2 Uncharacterized protein Q8N9H9/rs1281018 C1orf127 A530V - 2* 3 235 6 2 Q8N9T8/rs34743532 Protein KRI1 homolog S309L - 3 2^ 168 N/A 1 Q8NEV8/rs17108127 Exophilin-5 M512L - 2* 2^ 256 6 1 Q8NEV8/rs2640785 Exophilin-5 E137V - 2 2^ 53 5 1 Q8NEV8/rs3741046 Exophilin-5 R118L - 2* 2^ 53 5 1 Fibronectin type III domain- Q8TBE3/rs17054522 containing protein 9 P166A - 3* 2^ 42 8 2 Q8TBZ2/rs9890721 MYCBP-associated protein R688W - 4 2^ 45 N/A 3 Coiled-coil alpha-helical rod Q8TD31/rs130066 protein 1 S164R - 2 2^ 166 6 1 Coiled-coil alpha-helical rod Q8TD31/rs130068 protein 1 R417W - 2* 3 45 5 1 Coiled-coil alpha-helical rod Q8TD31/rs130079 protein 1 G575C - 2 2^ 151 6 1 Coiled-coil alpha-helical rod Q8TD31/rs2073720 protein 1 K546R - 2* 2^ 152 6 1
7 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Guanine nucleotide exchange Q8TEV9/rs8080966 protein SMCR8 P524L - 2* 4 166 4 1 Folliculin-interacting protein Q8TF40/rs12109782 1 V738L - 2* 2^ 32 5 1 Dendritic cell nuclear protein Q8TF63/rs12520809 1 N97D - 2 2^ 40 5 2 Nucleolar complex protein 3 Q8WTT2/rs12572897 homolog P194L - 2* 3 138 6 2 U4/U6.U5 small nuclear ribonucleoprotein 27 kDa Q8WVK2/- protein S114F - 2* 3 135 4 2 T-complex protein 11 Q8WWU5/rs2234045 homolog G253A - 2* 2^ 48 6 2 Q8WXD2/rs35664837 Secretogranin-3 M233V - 2* 3 46 5 2 Q8WXH2/rs17853661 Junctophilin-3 P645L - 4 2^ 127 6 3 Q92504/rs35690712 Zinc transporter SLC39A7 G124R - 2 2^ 90 4 2 Q96FF9/rs34020666 Sororin S156Y - 2 2^ 131 6 1 Centrosomal protein of 95 Q96GE4/rs9910506 kDa M165I - 2 2^ 100 4 1 Q96KD3/rs6949056 Protein FAM71F1 S228L - 3* 2^ 42 7 1 Uncharacterized protein Q96LP6/rs7484376 C12orf42 P182R - 2* 2^ 68 5 1 Centrosomal protein Q96M02/rs11558415 C10orf90 M57I - 2 3 79 5 1 Ribonucleases P/MRP protein Q99575/rs3824145 subunit POP1 S127L - 2* 3^ 65 5 2 Cardiomyopathy; familial hypertrophic 17 (CMH17) Q9BR39/rs387906898 Junctophilin-2 S165F [MIM:613873] 4 2^ 64 7 4 Q9BW71/rs11643314 HIRA-interacting protein 3 G521W - 4 2^ 51 9 3 Q9BW71/rs35431046 HIRA-interacting protein 3 A496V - 2 3 58 4 1 Q9BWW9/rs2076672 Apolipoprotein L5 T323M - 2* 2^ 114 6 2
8 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Q9H0A9/rs884134 Speriolin-like protein P113L - 4 2^ 72 7 3 Uncharacterized protein Q9H0B3/rs2277921 KIAA1683 P835L - 2* 2^ 120 6 2 RIB43A-like with coiled- Q9H4K1/rs2142661 coils protein 2 R180C - 3* 3 68 6 1 Q9H799/rs16903518 Protein JBTS17 P2592L - 3 2^ 99 5 2 Q9H799/rs377107065 Protein JBTS17 P2750S - 2 2^ 50 4 1 Q9HAW4/rs34390044 Claspin P892T - 2* 3 234 6 1 Q9HBH7/rs1045082 Protein BEX1 M66I - 2 3 43 4 1 Q9HBH7/rs709036 Protein BEX1 A40V - 2* 2^ 40 7 2 Uncharacterized protein Q9HCM1/rs3759299 KIAA1551 S1208C - 3 2^ 130 7 1 Uncharacterized protein Q9HCM1/rs61353224 KIAA1551 P147S - 2* 2^ 30 4 1 Q9HCM3/rs2774960 UPF0606 protein KIAA1549 P652L - 2 2^ 117 5 2 Q9NSI2/rs3737075 Protein FAM207A V212L - 2* 2^ 71 5 1 Spermatogenesis-associated Q9NWH7/rs1338314 protein 6 R333W - 2 2^ 154 5 2 Sperm protein associated with the nucleus on the X Q9NY87/- chromosome C V59F - 2* 2^ 95 N/A 2 Nuclear pore-associated Q9NZP6/rs36025315 protein 1 P343A - 2* 2^ 229 5 1 Centrosomal protein of 126 Q9P2H0/rs7926728 kDa G238C - 2* 3 147 3 1 Putative TP73 antisense gene Q9UF72/rs35766062 protein 1 P120L - 2 3^ 66 N/A 1 Q9UKA4/rs17063163 A-kinase anchor protein 11 H1070R - 2 2^ 99 4 1 Transmembrane and coiled- Q9ULS5/rs17854038 coil domain protein 3 P232Q - 2* 3 32 6 1
9 Average # disorder # disorder # disorder # order UniProt/dbSNP Protein Mutation Disease length of predictors predictors predictorsb predictorsc LDRd in D2P2e for LDRf Uncharacterized protein Q9UPP5/rs7523552 KIAA1107 N715Y - 3 2^ 183 N/A 1 Deleted in lung and Q9Y238/rs9840172 esophageal cancer protein 1 N1150D - 2 2^ 35 5 1 Mediator of RNA polymerase Q9Y2X0/rs34859566 II transcription subunit 16 L770F - 2* 2^ 32 5 1 von Willebrand factor A Q9Y334/rs28400001 domain-containing protein 7 R711C - 2* 2^ 52 5 1 Small kinetochore-associated Q9Y448/rs7169404 protein R75L - 2 4 81 4 1 Coiled-coil-helix-coiled-coil- Q9Y6H1/rs86430965 helix domain-containing Parkinson disease 22 0 protein 2 T61I (PARK22) [MIM:616710] 2* 3 92 7 2 aColumns 1 and 2 describe the protein accession numbers in the UniProt database/dbSNP database and protein names, respectively. Column 3 indicates the DO mutations, which can be described as X?Y, where X is the wild-type residue, Y is the mutated residue and ? is the position. The disease annotations of mutations are shown in column 4. Columns 5 and 6 list the numbers of predictors that agree the mutations to located in disordered (column 5)/ordered (column 6) regions. The column 7 shows the lengths of predicted LDRs are the average length of predicted disordered regions from all the 4 (VSL2B, IUPred-short, IUPred-long and DynaMine) predictors. We considered the prediction result to be ‘ordered’ if the score from DynaMine is larger than 0.8 and ‘disordered’ if the score is smaller than 0.69. bNumber of predictors that agreed that the wild-type residues are located in disordered region. cNumber of predictors that agreed that the mutations are located in ordered region. dAveraged length of disordered regions from different predictors. eNumber of predictors (out of nine) that agreed that the wild-type residues are located in disordered region according to the prediction results from D2P2 database. ‘N/A’ denotes that the prediction results for current protein could not be found. fAmong the predictors agreeing that the wild-type residues are located in disordered region, the number of predictor predicting long disordered regions (>=30 amino acids) *The predicted score of DynaMine for the wild-type residue is between 0.69 and 0.8, which means the prediction is context dependent. Therefore this prediction result was not taking into consideration. As such, the total number of predictors for this entry was 3. ^The predicted score of DynaMine for the mutation is between 0.69 and 0.8, which means the prediction is context dependent. Therefore this prediction result was not taking into consideration. As such, the total number of predictors for this entry was 3.
10 Table S3 ELM mapping results for DO disease and non-disease mutations
ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
Disease mutation Congenital bilateral absence of the vas P13569 R766M deferens (CBAVD) [MIM:277180] LIG 766 770 ARR*MQSVL*NLM
P35222 D32Y Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*YSGIHS*GAT
P35222 D32Y Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLYSGIHS*GAT
P35222 S33F Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*DFGIHS*GAT
P35222 S33F Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLDFGIHS*GAT
P35222 S33Y Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*DYGIHS*GAT
P35222 S33Y Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLDYGIHS*GAT
P35222 S37C Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*DSGIHC*GAT
P35222 S37C Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLDSGIHC*GAT
P35222 S37F Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*DSGIHF*GAT
P35222 S37F Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLDSGIHF*GAT
P35222 S37C Ovarian cancer (OC) [MIM:167000] DEG 32 37 SYL*DSGIHC*GAT
P35222 S37C Ovarian cancer (OC) [MIM:167000] MOD 30 37 QQS*YLDSGIHC*GAT
P35222 S33F Medulloblastoma (MDB) [MIM:155255] DEG 32 37 SYL*DFGIHS*GAT
P35222 S33F Medulloblastoma (MDB) [MIM:155255] MOD 30 37 QQS*YLDFGIHS*GAT
P35222 D32Y Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*YSGIHS*GAT
P35222 D32Y Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLYSGIHS*GAT Pilomatrixoma (PTR) [MIM:132600] P35222 S33F Medulloblastoma (MDB) [MIM:155255] DEG 32 37 SYL*DFGIHS*GAT Pilomatrixoma (PTR) [MIM:132600] P35222 S33F Medulloblastoma (MDB) [MIM:155255] MOD 30 37 QQS*YLDFGIHS*GAT Colorectal cancer (CRC) [MIM:114500] P35222 S33Y Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*DYGIHS*GAT Colorectal cancer (CRC) [MIM:114500] P35222 S33Y Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLDYGIHS*GAT Leukemia; acute lymphoblastic; 3 (ALL3) Q02548 G183S [MIM:613065] LIG 178 186 AGS*SYSISSILG*ITS Erythrocytosis; familial; 4 (ECYT4) Q99814 M535V [MIM:611783] DEG 529 542 LET*LAPYIPVDGEDFQL*SPI
Non-disease mutation
P09619 N718Y - LIG 716 719 AEL*YSYA*LPV
P35222 G34V - DEG 32 37 SYL*DSVIHS*GAT
P35222 G34V - MOD 30 37 QQS*YLDSVIHS*GAT
Q02548 G183V - LIG 178 186 AGS*SYSISVILG*ITS
Q8WXE1 P240L - LIG 238 242 PEA*CSLQF*GKT Q96RU8 E360A - DEG 354 361 IGT*SDQIVPAY*QED
* The MIM number is the accession number from the Online Mendelian Inheritance in Man database (OMIM) [2]. The OMIM numbers can be used as a keyword when searching for diseases.
Mutations found in disease samples and somatic mutations do not have OMIM numbers in the “Human polymorphisms and disease mutations dataset [1]”.
11 ^ ELM types: CLV: Cleavage sites; DEG: degradation sites; DOC: docking sites; LIG: ligand binding sites; MOD: post-translational modification sites; TRG: targeting sites.
12 Table S4 ELM mapping results for OD disease and non-disease mutations
ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
Disease mutation
P13569 V754M Cystic fibrosis (CF) [MIM:219700] LIG 751 755 ILP*RISMI*STG
P00740 C108S Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*SKDDINSYECWC*PFG Gerstmann-Straussler disease (GSD) P04156 F198S [MIM:137440] MOD 196 201 TKG*ENSTET*DVK
Non-disease mutation
Not found.
13 Table S5 ELM mapping results for DD disease and non-disease mutations
ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
Disease mutation Usher syndrome 1G (USH1G) Q495M9 D458V [MIM:606943] LIG 456 461 PPA*LEVTEL* Thrombocytopenia 6 (THC6) P12931 E527K [MIM:616937] MOD 526 534 FTS*TKPQYQPGE*NL Pseudohypoaldosteronism 2B Q96J92 E562K (PHA2B) [MIM:614491] DEG 557 566 FPP*EPEEPKADQH*QPF Pseudohypoaldosteronism 2B Q96J92 D564A (PHA2B) [MIM:614491] DEG 557 566 FPP*EPEEPEAAQH*QPF Pseudohypoaldosteronism 2B Q96J92 Q565E (PHA2B) [MIM:614491] DEG 557 566 FPP*EPEEPEADEH*QPF
P35222 D32G Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*GSGIHS*GAT
P35222 D32G Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLGSGIHS*GAT
P35222 G34E Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*DSEIHS*GAT
P35222 G34E Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLDSEIHS*GAT Noonan syndrome 5 (NS5) P04049 R256S [MIM:611553] LIG 254 263 LSQ*RQSSTSTPNV*HMV Noonan syndrome 5 (NS5) P04049 R256S [MIM:611553] MOD 254 262 LSQ*RQSSTSTPN*VHM Noonan syndrome 5 (NS5) P04049 S257L [MIM:611553] LIG 254 263 LSQ*RQRLTSTPNV*HMV Noonan syndrome 5 (NS5) P04049 S257L [MIM:611553] MOD 254 262 LSQ*RQRLTSTPN*VHM Noonan syndrome 5 (NS5) P04049 S259F [MIM:611553] LIG 254 263 LSQ*RQRSTFTPNV*HMV Noonan syndrome 5 (NS5) P04049 S259F [MIM:611553] MOD 254 262 LSQ*RQRSTFTPN*VHM Noonan syndrome 5 (NS5) P04049 T260R [MIM:611553] LIG 254 263 LSQ*RQRSTSRPNV*HMV Noonan syndrome 5 (NS5) P04049 T260R [MIM:611553] MOD 254 262 LSQ*RQRSTSRPN*VHM Noonan syndrome 5 (NS5) P04049 P261A [MIM:611553] LIG 254 263 LSQ*RQRSTSTANV*HMV Noonan syndrome 5 (NS5) P04049 P261A [MIM:611553] MOD 254 262 LSQ*RQRSTSTAN*VHM Noonan syndrome 5 (NS5) P04049 P261L [MIM:611553] LIG 254 263 LSQ*RQRSTSTLNV*HMV Noonan syndrome 5 (NS5) P04049 P261L [MIM:611553] MOD 254 262 LSQ*RQRSTSTLN*VHM Noonan syndrome 5 (NS5) P04049 P261S [MIM:611553] LIG 254 263 LSQ*RQRSTSTSNV*HMV Noonan syndrome 5 (NS5) P04049 P261S [MIM:611553] MOD 254 262 LSQ*RQRSTSTSN*VHM Noonan syndrome 5 (NS5) P04049 V263A [MIM:611553] LIG 254 263 LSQ*RQRSTSTPNA*HMV Non-syndromic orofacial cleft 11 P12644 R287H (OFC11) [MIM:600625] CLV 287 293 LTR*HRRAKRS*PKH Medulloblastoma (MDB) P35222 S37A [MIM:155255] DEG 32 37 SYL*DSGIHA*GAT Medulloblastoma (MDB) P35222 S37A [MIM:155255] MOD 30 37 QQS*YLDSGIHA*GAT Liddle syndrome (LIDLS) P51168 P617S [MIM:177200] LIG 617 620 GTP*SPNY*DSL Liddle syndrome (LIDLS) P51168 P618R [MIM:177200] LIG 617 620 GTP*PRNY*DSL Liddle syndrome (LIDLS) P51168 Y620H [MIM:177200] LIG 617 620 GTP*PPNH*DSL Li-Fraumeni syndrome (LFS) P04637 P309S [MIM:151623] TRG 305 323 GST*KRALSNNTSSSPQPKKKPL*DGE Li-Fraumeni syndrome (LFS) P04637 P82L [MIM:151623] DOC 78 83 PAP*AAPTLA*APA Li-Fraumeni syndrome (LFS) P04637 R306P [MIM:151623] TRG 305 323 GST*KPALPNNTSSSPQPKKKPL*DGE Li-Fraumeni syndrome (LFS) P04637 L344P [MIM:151623] TRG 339 352 ERF*EMFREPNEALELKD*AQA
14 ELM UniProt Mutation Disease* Start End Motif (within*…*) type^ LEOPARD syndrome 2 (LPRD2) P04049 S257L [MIM:611554] LIG 254 263 LSQ*RQRLTSTPNV*HMV LEOPARD syndrome 2 (LPRD2) P04049 S257L [MIM:611554] MOD 254 262 LSQ*RQRLTSTPN*VHM Intrauterine growth retardation; metaphyseal dysplasia; adrenal hypoplasia congenita; and genital P49918 D274N anomalies (IMAGE) [MIM:614732] DEG 270 282 LSG*PLISNFFAKRKRS*APE Intrauterine growth retardation; metaphyseal dysplasia; adrenal hypoplasia congenita; and genital P49918 F276S anomalies (IMAGE) [MIM:614732] DEG 270 282 LSG*PLISDFSAKRKRS*APE Intrauterine growth retardation; metaphyseal dysplasia; adrenal hypoplasia congenita; and genital P49918 F276V anomalies (IMAGE) [MIM:614732] DEG 270 282 LSG*PLISDFVAKRKRS*APE Intrauterine growth retardation; metaphyseal dysplasia; adrenal hypoplasia congenita; and genital P49918 K278E anomalies (IMAGE) [MIM:614732] DEG 270 282 LSG*PLISDFFAERKRS*APE Intrauterine growth retardation; metaphyseal dysplasia; adrenal hypoplasia congenita; and genital P49918 R279P anomalies (IMAGE) [MIM:614732] DEG 270 282 LSG*PLISDFFAKPKRS*APE Holoprosencephaly 4 (HPE4) Q15583 S157C [MIM:142946] LIG 153 157 MDI*PLDLC*SSA
P35222 D32G Pilomatrixoma (PTR) [MIM:132600] DEG 32 37 SYL*GSGIHS*GAT
P35222 D32G Pilomatrixoma (PTR) [MIM:132600] MOD 30 37 QQS*YLGSGIHS*GAT Medulloblastoma (MDB) P35222 S37A [MIM:155255] DEG 32 37 SYL*DSGIHA*GAT Medulloblastoma (MDB) P35222 S37A [MIM:155255] MOD 30 37 QQS*YLDSGIHA*GAT Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 Q13501 P348L (FTDALS3) [MIM:616437] DEG 347 352 KEV*DLSTGE*LQS Erythrocytosis; familial; 4 (ECYT4) Q99814 M535T [MIM:611783] DEG 529 542 LET*LAPYIPTDGEDFQL*SPI Erythrocytosis; familial; 4 (ECYT4) Q99814 F540L [MIM:611783] DEG 529 542 LET*LAPYIPMDGEDLQL*SPI Ectodermal dysplasia; anhidrotic; with T-cell immunodeficiency autosomal dominant (ADEDAID) P25963 S32I [MIM:612132] DEG 31 36 DRH*DIGLDS*MKD Creutzfeldt-Jakob disease (CJD) P04156 E196K [MIM:123400] MOD 196 201 TKG*KNFTET*DVK Congenital bilateral absence of the vas P13569 R792G deferens (CBAVD) [MIM:277180] LIG 792 797 AST*GKVSLA*PQA CHOPS syndrome (CHOPS) Q9UHB7 T254A [MIM:616368] DEG 252 260 MLQ*KPAAYVRPM*DGQ CHOPS syndrome (CHOPS) Q9UHB7 T254S [MIM:616368] DEG 252 260 MLQ*KPSAYVRPM*DGQ CHOPS syndrome (CHOPS) Q9UHB7 R258W [MIM:616368] DEG 252 260 MLQ*KPTAYVWPM*DGQ
P78314 R415P Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QPSPPDGQ*SFR
P78314 R415Q Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QQSPPDGQ*SFR
P78314 P418H Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QRSPHDGQ*SFR
P78314 P418L Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QRSPLDGQ*SFR
P78314 P418R Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QRSPRDGQ*SFR
P78314 G420E Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QRSPPDEQ*SFR
P78314 G420R Cherubism (CRBM) [MIM:118400] DOC 414 421 PHL*QRSPPDRQ*SFR
Non-disease mutation
O95081 T365N - LIG 365 369 GAF*NNPFT*APA
Q92934 A107S - LIG 106 122 NLW*ASQRYGRELRRMSDEFV*DSF
15 ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
Q9UQB8 Q519R - LIG 516 521 NPF*AHVRLK*PTV
O43683 N534D - DEG 534 538 EDG*DKENY*GLP
Q9H0W5 K507N - LIG 500 509 WHT*PRLPTLPNRV*PRA
P38936 D149G - DEG 145 157 RRQ*TSMTGFYHSKRRL*IFS
P38936 D149G - LIG 144 153 KRR*QTSMTGFYHS*KRR
P38936 D149G - TRG 142 158 GRK*RRQTSMTGFYHSKRRLI*FSK
O00418 Q361R - MOD 356 363 TEE*KCGSPRVR*TLS
P04921 K124E - LIG 123 128 DSS*REEYFI*
P06213 Y1361C - LIG 1361 1364 HIP*CTHM*NGG
P43630 T397M - LIG 396 401 PQE*VMYAQL*DHC
O15151 T406I - MOD 400 406 LAH*SSESQEI*ISS
Q9BUB5 R446Q - DOC 434 448 LCS*MKLSPPCKSRLAQRR*ALA
P01106 A322V - TRG 322 328 YPA*VKRVKLD*SVR
P01106 A322V - TRG 320 327 KDY*PAVKRVKL*DSV
Q6T4R5 A1628P - DOC 1626 1631 NTP*MQPISE*GET
P48552 I441V - LIG 440 444 NCV*PVDLS*CKH
P30559 A16S - MOD 14 19 AEA*ANSSAA*PPG
Q13492 F641L - LIG 638 642 MRP*PNPLG*PVS
Q96BK5 E315A - MOD 314 320 DAT*LAETLVK*KKK
P04049 T260I - LIG 254 263 LSQ*RQRSTSIPNV*HMV
P04049 T260I - MOD 254 262 LSQ*RQRSTSIPN*VHM
Q13464 T1112P - CLV 1110 1114 PSA*DEPDG*NLP
O94979 P841L - LIG 839 843 ENP*PPLGF*IMH
Q9NZC9 A22G - LIG 12 27 QRK*KIEENRQKALGRRAEK*LLA
P08047 T737A - MOD 736 742 EGS*GAATPSA*LIT
Q13501 S349T - DEG 347 352 KEV*DPTTGE*LQS
Q9Y5M8 V9L - TRG 7 9 ADS*RRL*ADG
P04637 G360A - DOC 359 363 GKE*PAGSR*AHS
Q96RU8 E360D - DEG 354 361 IGT*SDQIVPDY*QED
Q71U36 E447K - LIG 443 451 VEG*EGEEKGEEY*
P13051 Q4R - LIG 4 13 MIG*RKTLYSFFSP*SPA
Q9H4A3 R1957H - DOC 1957 1961 KVG*HFSVS*KTE
16 Table S6 ELM mapping results for OO disease and non-disease mutations
ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
Disease mutation
O76024 P504L Wolfram syndrome 1 (WFS1) [MIM:222300] MOD 499 504 LVV*LNVSVL*CLL Von Willebrand disease 1 (VWD1) P04275 C1149R [MIM:193400] MOD 1147 1149 WRY*NSR*APA
P78363 S445R Stargardt disease 1 (STGD1) [MIM:248200] MOD 443 448 YFF*DNRTQM*NMI
P78363 D1532N Stargardt disease 1 (STGD1) [MIM:248200] MOD 1528 1533 LTD*RNISNF*LVK
P78363 S100P Stargardt disease 1 (STGD1) [MIM:248200] MOD 97 102 VSN*YNNPIL*ARV Spongiform encephalopathy with P04156 T183A neuropsychiatric features (SENF) [MIM:606688] MOD 180 185 HDC*VNIAIK*QHT Rabson-Mendenhall syndrome (RMS) P06213 P997T [MIM:262190] LIG 993 999 PLY*ASSNTEY*LSA
O43464 R404W Parkinson disease 13 (PARK13) [MIM:610297] MOD 397 404 HKV*ILGSPAHW*AGL KHE*EVLAMVIQRAFRRHLL Q14524 S1904L Long QT syndrome 3 (LQT3) [MIM:603830] LIG 1902 1921 QRSL*KHA KHE*EVSAMVIRRAFRRHLL Q14524 Q1909R Long QT syndrome 3 (LQT3) [MIM:603830] LIG 1902 1921 QRSL*KHA Kosaki overgrowth syndrome (KOGS) P09619 P584R [MIM:616592] LIG 581 584 EYI*YVDR*MQL
O14686 R5340L Kabuki syndrome 1 (KABUK1) [MIM:147920] LIG 5338 5344 PTG*CALSEPK*ILT Immunodeficiency with hyper-IgM 2 (HIGM2) Q9GZX7 R24W [MIM:605258] MOD 24 30 AKG*WRETYLC*YVV
P02786 Y20H Immunodeficiency 46 (IMD46) [MIM:616740] TRG 20 23 PLS*HTRF*SLA Hypocalcemia; autosomal dominant 1 P41180 C131W (HYPOC1) [MIM:601198] MOD 129 134 DEF*CNWSEH*IPS Hypocalcemia; autosomal dominant 1 P41180 C129R (HYPOC1) [MIM:601198] MOD 129 134 DEF*RNCSEH*IPS
P00740 C97S Hemophilia B (HEMB) [MIM:306900] MOD 97 102 GDQ*SESNPC*LNG
P00740 P101R Hemophilia B (HEMB) [MIM:306900] MOD 97 102 GDQ*CESNRC*LNG
P00740 C102R Hemophilia B (HEMB) [MIM:306900] MOD 97 102 GDQ*CESNPR*LNG
P00740 D110N Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*CKNDINSYECWC*PFG
P00740 I112S Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*CKDDSNSYECWC*PFG
P00740 N113K Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*CKDDIKSYECWC*PFG
P00740 Y115C Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*CKDDINSCECWC*PFG
P00740 C119F Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*CKDDINSYECWF*PFG
P00740 C119R Hemophilia B (HEMB) [MIM:306900] MOD 108 119 GGS*CKDDINSYECWR*PFG Familial hypercholesterolemia (FH) P01130 Y828C [MIM:143890] LIG 822 829 NSI*NFDNPVCQ*KTT Familial hypercholesterolemia (FH) P01130 P826S [MIM:143890] LIG 822 829 NSI*NFDNSVYQ*KTT Familial hypercholesterolemia (FH) P01130 N825K [MIM:143890] LIG 822 829 NSI*NFDKPVYQ*KTT Familial adenomatous polyposis (FAP) P25054 S171I [MIM:175100] TRG 163 176 AQL*QNLTKRIDILPLTE*NFS Erythrocytosis; familial; 4 (ECYT4) Q99814 G537W [MIM:611783] DEG 529 542 LET*LAPYIPMDWEDFQL*SPI Erythrocytosis; familial; 4 (ECYT4) Q99814 P534L [MIM:611783] DEG 529 542 LET*LAPYILMDGEDFQL*SPI Erythrocytosis; familial; 4 (ECYT4) Q99814 G537R [MIM:611783] DEG 529 542 LET*LAPYIPMDREDFQL*SPI
Q9NVV9 N136K Dystonia 6; torsion (DYT6) [MIM:602629] LIG 134 137 VFC*DHKY*TVE
Q9NVV9 N136S Dystonia 6; torsion (DYT6) [MIM:602629] LIG 134 137 VFC*DHSY*TVE
Q9NVV9 Y137C Dystonia 6; torsion (DYT6) [MIM:602629] LIG 134 137 VFC*DHNC*TVE
P13569 R553Q Cystic fibrosis (CF) [MIM:219700] TRG 553 556 GGQ*QARI*SLA
17 ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
P04156 V180I Creutzfeldt-Jakob disease (CJD) [MIM:123400] MOD 180 185 HDC*INITIK*QHT
P04156 E200K Creutzfeldt-Jakob disease (CJD) [MIM:123400] MOD 196 201 TKG*ENFTKT*DVK Congenital insensitivity to pain with anhidrosis P04629 E492K (CIPA) [MIM:256800] LIG 490 496 QGH*IIKNPQY*FSD
P51587 F32L Breast cancer (BC) [MIM:114480] LIG 27 35 LGP*ISLNWLEEL*SSE
P51587 W31C Breast cancer (BC) [MIM:114480] LIG 27 35 LGP*ISLNCFEEL*SSE
P51587 W31R Breast cancer (BC) [MIM:114480] LIG 27 35 LGP*ISLNRFEEL*SSE Bartter syndrome 2; antenatal (BARTS2) P48048 V315G [MIM:241200] MOD 310 316 TCQ*VRTSYGP*EEV Bartter syndrome 2; antenatal (BARTS2) P48048 S219R [MIM:241200] MOD 216 222 VAN*LRKRLLI*GSH 3-methylglutaconic aciduria 8 (MGCA8) O43464 R404Q [MIM:617248] MOD 397 404 HKV*ILGSPAHQ*AGL
Non-disease mutation
Q9GZX7 R25C - MOD 24 30 AKG*RCETYLC*YVV
O14965 M373V - DEG 370 378 NPS*QRPVLREVL*EHP VGK*FYATFLIQEHFRKFMKC Q13698 R1539C - LIG 1523 1542 QEE*YYG
P55211 R192C - MOD 191 199 EKL*RCRFSSLHF*MVE LRN*DRVYQPLRDRDDAQYS P04234 Q147R - LIG 146 163 HL*GGN
Q99741 V441I - CLV 439 443 QVI*SEIDG*NRM
Q13111 M239V - LIG 238 242 GKV*PVVVL*QDI
P28562 A56T - DOC 54 62 IVR*RRTKGAMGL*EHI ILN*SYAGLACVEEPSDMITES P32519 N58S - LIG 47 67 SLD*VAE
O43464 G399S - MOD 397 404 HKV*ILSSPAHR*AGL
O14920 F734L - MOD 730 736 VRE*QDQSLTA*LDW
O14920 A736T - MOD 730 736 VRE*QDQSFTT*LDW
P24394 A492T - LIG 491 497 PLV*ITGNPAY*RSF
P24394 A492V - LIG 491 497 PLV*IVGNPAY*RSF
P06213 I1023F - TRG 1021 1026 VSR*EKFTLL*REL
P01130 V827I - LIG 822 829 NSI*NFDNPIYQ*KTT
Q9HBG7 M602V - LIG 599 606 VVG*ENTVYAQV*FNL DVK*EEMTSALSTMRVDYE* P49137 A361S - TRG 354 368 QIK
Q01726 R160W - TRG 160 163 TLP*WARR*AVA
Q01726 R163Q - TRG 160 163 TLP*RARQ*AVA
Q01726 R162P - TRG 160 163 TLP*RAPR*AVA
P52701 K13T - LIG 4 13 MSR*QSTLYSFFPT*SPA
Q99572 R578Q - TRG 575 578 CCR*WRIQ*KEF KHE*EVSAMVIQRAFRRHLL Q14524 R1919C - LIG 1902 1921 QCSL*KHA
Q9NQ25 T302M - LIG 300 307 EDP*ANMVYSTV*EIP
P02730 R646Q - MOD 641 646 FKV*SNSSAQ*GWV
P02730 R646W - MOD 641 646 FKV*SNSSAW*GWV
P21452 I23T - MOD 18 23 GPE*SNTTGT*TAF
P01266 G815R - MOD 815 820 AAS*RNFSLF*IQS
18 ELM UniProt Mutation Disease* Start End Motif (within*…*) type^
P01266 S1222L - MOD 1219 1224 PLP*FNALEV*VGG
19 Table S7. Pfam [3] domain mapping results for DO disease and non-disease mutations
UniProt Mutation Disease Start End Domain
Disease mutation
O00754 S453Y Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 386 465 Alpha-mann_mid
O00754 G801D Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 510 1001 Glyco_hydro_38C
O00754 G451C Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 386 465 Alpha-mann_mid
O00754 S453F Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 386 465 Alpha-mann_mid
O00754 G800R Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 510 1001 Glyco_hydro_38C
O00754 G800W Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 510 1001 Glyco_hydro_38C Nephrolithiasis/osteoporosis; hypophosphatemic; 2 O14745 E68A (NPHLOP2) [MIM:612287] 16 91 PDZ
O14832 P173S Refsum disease (RD) [MIM:266500] 61 277 PhyH
O14832 H220Y Refsum disease (RD) [MIM:266500] 61 277 PhyH Congenital disorder of glycosylation 1A (CDG1A) O15305 N216I [MIM:212065] 28 246 PMM Congenital disorder of glycosylation 1A (CDG1A) O15305 H218L [MIM:212065] 28 246 PMM Familial Mediterranean fever; autosomal recessive (ARFMF) O15553 R42W [MIM:249100] 8 84 PYRIN
O43186 R90W Leber congenital amaurosis 7 (LCA7) [MIM:613829] 40 96 Homeobox
O43395 P493S Retinitis pigmentosa 18 (RP18) [MIM:601414] 308 521 PRP3
O43405 G87V Deafness; autosomal dominant; 9 (DFNA9) [MIM:601369] 32 121 LCCL
O43405 G87W Deafness; autosomal dominant; 9 (DFNA9) [MIM:601369] 32 121 LCCL Muscular dystrophy-dystroglycanopathy congenital with brain O43505 A406V and eye anomalies A13 (MDDGA13) [MIM:615287] 94 409 Glyco_transf_49
O60500 P575Q Nephrotic syndrome 1 (NPHS1) [MIM:256300] 548 634 C2-set_2
O60663 A253V Nail-patella syndrome (NPS) [MIM:161200] 220 276 Homeobox Neurodegeneration with brain iron accumulation 2B O60733 R632W (NBIA2B) [MIM:610217] 481 665 Patatin Cardiomyopathy; dilated 1C; with or without left ventricular O75112 T206I non-compaction (CMD1C) [MIM:601493] 192 297 DUF4749 Pituitary hormone deficiency; combined; 2 (CPHD2) O75360 R120C [MIM:262600] 70 126 Homeobox Pituitary hormone deficiency; combined; 2 (CPHD2) O75360 R125W [MIM:262600] 70 126 Homeobox
O75444 Q303L Cataract 21; multiple types (CTRCT21) [MIM:610202] 261 352 bZIP_Maf
O75445 R334W Usher syndrome 2A (USH2A) [MIM:276901] 292 516 Laminin_N
O94906 R729W Retinitis pigmentosa 60 (RP60) [MIM:613983] 709 740 TPR_8
O95255 G755R Pseudoxanthoma elasticum (PXE) [MIM:264800] 646 781 ABC_tran
O95343 G244C Holoprosencephaly 2 (HPE2) [MIM:157170] 207 263 Homeobox Spastic paraplegia 77; autosomal recessive (SPG77) O95363 D142Y [MIM:617046] 70 210 tRNA-synt_2d High density lipoprotein deficiency 1 (HDLD1) O95477 A937V [MIM:205400] 916 1061 ABC_tran
P00441 D125V Amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400] 9 150 Sod_Cu
P00451 G130R Hemophilia A (HEMA) [MIM:306700] 88 202 Cu-oxidase_3 Ornithine carbamoyltransferase deficiency (OTCD) P00480 P220A [MIM:311250] 187 341 OTCace Hemolytic anemia due to adenylate kinase deficiency P00568 R128W (HAAKD) [MIM:612631] 13 169 ADK
P00740 R404T Hemophilia B (HEMB) [MIM:306900] 227 454 Trypsin
P00740 S411I Hemophilia B (HEMB) [MIM:306900] 227 454 Trypsin
20 UniProt Mutation Disease Start End Domain
P00740 P414T Hemophilia B (HEMB) [MIM:306900] 227 454 Trypsin
P00742 R366C Factor X deficiency (FA10D) [MIM:227600] 235 462 Trypsin
P00742 G421D Factor X deficiency (FA10D) [MIM:227600] 235 462 Trypsin
P00966 G117S Citrullinemia 1 (CTLN1) [MIM:215700] 8 403 Arginosuc_synth
P00966 G117D Citrullinemia 1 (CTLN1) [MIM:215700] 8 403 Arginosuc_synth
P00966 T119I Citrullinemia 1 (CTLN1) [MIM:215700] 8 403 Arginosuc_synth
P00966 G117C Citrullinemia 1 (CTLN1) [MIM:215700] 8 403 Arginosuc_synth
P01008 P461L Antithrombin III deficiency (AT3D) [MIM:613118] 85 461 Serpin
P01130 G592E Familial hypercholesterolemia (FH) [MIM:143890] 573 615 Ldl_recept_b
P01185 G48V Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 G93W Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 G96C Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 G96V Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 G96D Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5 Epidermolysis bullosa simplex; Weber-Cockayne type (WC- P02533 R388C EBS) [MIM:131800] 114 425 Filament Muscular dystrophy congenital LMNA-related (MDCL) P02545 R249W [MIM:613205] 30 386 Filament Hutchinson-Gilford progeria syndrome (HGPS) P02545 R471C [MIM:176670] 433 544 LTD Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 R453W (EDMD2) [MIM:181350] 433 544 LTD Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 N456I (EDMD2) [MIM:181350] 433 544 LTD Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 R249W (EDMD2) [MIM:181350] 30 386 Filament Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 D461Y (EDMD2) [MIM:181350] 433 544 LTD
P02545 E203G Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament
P02545 R190W Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament
P02545 E203K Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament
P02545 E317K Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament
P02545 L92F Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament Amyloidosis; transthyretin-related (AMYL-TTR) P02766 G67A [MIM:105210] 32 139 Transthyretin Amyloidosis; transthyretin-related (AMYL-TTR) P02766 G67R [MIM:105210] 32 139 Transthyretin Amyloidosis; transthyretin-related (AMYL-TTR) P02766 G67V [MIM:105210] 32 139 Transthyretin Amyloidosis; transthyretin-related (AMYL-TTR) P02766 S70I [MIM:105210] 32 139 Transthyretin Amyloidosis; transthyretin-related (AMYL-TTR) P02766 S70R [MIM:105210] 32 139 Transthyretin Amyloidosis; transthyretin-related (AMYL-TTR) P02766 T69I [MIM:105210] 32 139 Transthyretin
P03915 M237L Mitochondrial complex I deficiency (MT-C1D) [MIM:252010] 134 419 Proton_antipo_M
P03951 G263E Factor XI deficiency (FA11D) [MIM:612416] 200 283 PAN_1
P03951 S575L Factor XI deficiency (FA11D) [MIM:612416] 388 618 Trypsin
P04062 G232E Gaucher disease (GD) [MIM:230800] 117 466 Glyco_hydro_30 Hyperornithinemia with gyrate atrophy of choroid and retina P04181 H319Y (HOGA) [MIM:258870] 50 436 Aminotran_3
P04637 R175L Li-Fraumeni syndrome (LFS) [MIM:151623] 95 289 P53
P04637 R282W Li-Fraumeni syndrome (LFS) [MIM:151623] 95 289 P53
21 UniProt Mutation Disease Start End Domain
P04637 R283C Li-Fraumeni syndrome (LFS) [MIM:151623] 95 289 P53 Neuronopathy; distal hereditary motor; 2B (HMN2B) P04792 P182L [MIM:608634] 87 184 HSP20
P05089 T134I Argininemia (ARGIN) [MIM:207800] 6 305 Arginase
P05106 R240W Glanzmann thrombasthenia (GT) [MIM:273800] 133 381 Integrin_beta Macular degeneration; age-related; 13 (ARMD13) P05156 G119R [MIM:615439] 117 215 SRCR Hemolytic uremic syndrome atypical 3 (AHUS3) P05156 G119R [MIM:612923] 117 215 SRCR
P05186 G456R Hypophosphatasia infantile type (HOPSI) [MIM:241500] 51 490 Alk_phosphatase
P05186 A132V Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05186 R184W Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05186 R450C Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05186 G339R Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05787 G53V Cirrhosis (CIRRH) [MIM:215600] 2 87 Keratin_2_head
P06132 G170D Hepatoerythropoietic porphyria (HEP) [MIM:176100] 14 360 URO-D
P06213 R1119W Leprechaunism (LEPRCH) [MIM:246200] 1023 1290 Pkinase_Tyr
P06400 N803K Childhood cancer retinoblastoma (RB) [MIM:180200] 768 925 Rb_C
P06753 E151A Cap myopathy 1 (CAPM1) [MIM:609284] 49 285 Tropomyosin
P06858 S199C Lipoprotein lipase deficiency (LPL deficiency) [MIM:238600] 17 338 Lipase
P06858 S220R Lipoprotein lipase deficiency (LPL deficiency) [MIM:238600] 17 338 Lipase Thrombophilia due to protein S deficiency; autosomal P07225 G52D dominant (THPH5) [MIM:612336] 46 86 Gla
P07902 G83V Galactosemia (GALCT) [MIM:230400] 22 196 GalP_UDP_transf Pyruvate dehydrogenase E1-alpha deficiency (PDHAD) P08559 H292L [MIM:312170] 66 362 E1_dh Pyruvate dehydrogenase E1-alpha deficiency (PDHAD) P08559 R302C [MIM:312170] 66 362 E1_dh Hemolytic uremic syndrome atypical 1 (AHUS1) P08603 C630W [MIM:235400] 630 684 Sushi
P08709 G402R Factor VII deficiency (FA7D) [MIM:227500] 213 447 Trypsin Cardiomyopathy; familial hypertrophic 3 (CMH3) P09493 A63V [MIM:115196] 48 284 Tropomyosin
P10253 S529V Glycogen storage disease 2 (GSD2) [MIM:232300] 340 824 Glyco_hydro_31
P10636 P618L Frontotemporal dementia (FTD) [MIM:600274] 592 622 Tubulin-binding
P10912 S58L Laron syndrome (LARS) [MIM:262500] 43 144 EpoR_lig-bind
P11161 R359W Dejerine-Sottas syndrome (DSS) [MIM:145900] 340 364 zf-C2H2
P11161 R359W Charcot-Marie-Tooth disease 1D (CMT1D) [MIM:607678] 340 364 zf-C2H2
P11161 D383Y Charcot-Marie-Tooth disease 1D (CMT1D) [MIM:607678] 370 392 zf-C2H2
P11166 R232C Epilepsy; idiopathic generalized 12 (EIG12) [MIM:614847] 16 467 Sugar_tr
P11166 E243V Epilepsy; idiopathic generalized 12 (EIG12) [MIM:614847] 16 467 Sugar_tr Hypogonadotropic hypogonadism 2 with or without anosmia P11362 R78C (HH2) [MIM:147950] 38 116 ig Anemia; non-spherocytic hemolytic; due to G6PD deficiency P11413 S278F (NSHA) [MIM:300908] 212 510 G6PD_C Night blindness; congenital stationary; autosomal dominant 3 P11488 G38D (CSNBAD3) [MIM:610444] 9 339 G-alpha
P12644 S91C Non-syndromic orofacial cleft 11 (OFC11) [MIM:600625] 39 275 TGFb_propeptide Scapuloperoneal myopathy MYH7-related (SPMM) P12883 R1845W [MIM:181430] 843 1924 Myosin_tail_1 Myopathy; myosin storage; autosomal recessive (MSMB) P12883 R1820W [MIM:255160] 843 1924 Myosin_tail_1
22 UniProt Mutation Disease Start End Domain Myopathy; myosin storage; autosomal dominant (MSMA) P12883 R1845W [MIM:608358] 843 1924 Myosin_tail_1 Myopathy; myosin storage; autosomal dominant (MSMA) P12883 H1901L [MIM:608358] 843 1924 Myosin_tail_1 Cardiomyopathy; familial hypertrophic 1 (CMH1) P12883 M659I [MIM:192600] 87 766 Myosin_head Cardiomyopathy; familial hypertrophic 1 (CMH1) P12883 R1382W [MIM:192600] 843 1924 Myosin_tail_1 Cardiomyopathy; familial hypertrophic 1 (CMH1) P12883 E1555K [MIM:192600] 843 1924 Myosin_tail_1 Cardiomyopathy; familial hypertrophic 1 (CMH1) P12883 S148I [MIM:192600] 87 766 Myosin_head Cardiomyopathy; familial hypertrophic 1 (CMH1) P12883 P211L [MIM:192600] 87 766 Myosin_head Cardiomyopathy; familial hypertrophic 1 (CMH1) P12883 R1712W [MIM:192600] 843 1924 Myosin_tail_1
P12883 S642L Cardiomyopathy; dilated 1S (CMD1S) [MIM:613426] 87 766 Myosin_head
P12883 R1359C Cardiomyopathy; dilated 1S (CMD1S) [MIM:613426] 843 1924 Myosin_tail_1
P13569 G1249E Cystic fibrosis (CF) [MIM:219700] 1227 1374 ABC_tran Congenital bilateral absence of the vas deferens (CBAVD) P13569 R766M [MIM:277180] 639 849 CFTR_R
P14136 R276L Alexander disease (ALXDRD) [MIM:203450] 68 376 Filament
P14136 E332K Alexander disease (ALXDRD) [MIM:203450] 68 376 Filament Congenital sucrase-isomaltase deficiency (CSID) P14410 S594P [MIM:222900] 324 797 Glyco_hydro_31 Facial paresis; hereditary congenital; 3 (HCFP3) P14653 R207C [MIM:614744] 205 260 Homeobox
P14679 S361R Albinism; oculocutaneous; 1A (OCA1A) [MIM:203100] 170 403 Tyrosinase Hypomyelination with brainstem and spinal cord involvement P14868 D367Y and leg spasticity (HBSL) [MIM:615281] 175 496 tRNA-synt_2
P15289 G99D Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
P15289 R244C Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
P15289 G245R Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
P15289 P426L Leukodystrophy metachromatic (MLD) [MIM:250100] 368 502 Sulfatase_C
P15289 G99V Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
P15289 T408I Leukodystrophy metachromatic (MLD) [MIM:250100] 368 502 Sulfatase_C
P15289 T409I Leukodystrophy metachromatic (MLD) [MIM:250100] 368 502 Sulfatase_C
P15863 G166V Otofaciocervical syndrome 2 (OTFCS2) [MIM:615560] 98 222 PAX
P15884 R576W Pitt-Hopkins syndrome (PTHS) [MIM:610954] 565 618 HLH
P17405 G242R Niemann-Pick disease B (NPDB) [MIM:607616] 199 461 Metallophos
P17405 H319Y Niemann-Pick disease A (NPDA) [MIM:257200] 199 461 Metallophos
P17661 S13F Myopathy; myofibrillar; 1 (MFM1) [MIM:601419] 9 106 Filament_head
P18206 R975W Cardiomyopathy; dilated 1W (CMD1W) [MIM:611407] 918 1134 Vinculin
P19438 P75L Familial hibernian fever (FHF) [MIM:142680] 44 81 TNFR_c6
P19544 G253A Wilms tumor 1 (WT1) [MIM:194070] 1 321 WT1
P19544 R366C Wilms tumor 1 (WT1) [MIM:194070] 353 377 zf-C2H2
P19544 R394W Wilms tumor 1 (WT1) [MIM:194070] 383 405 zf-C2H2
P19544 R394L Wilms tumor 1 (WT1) [MIM:194070] 383 405 zf-C2H2
P19544 H377Y Nephrotic syndrome 4 (NPHS4) [MIM:256370] 353 377 zf-C2H2
P19544 R366C Meacham syndrome (MEACHS) [MIM:608978] 353 377 zf-C2H2
P19544 R394W Meacham syndrome (MEACHS) [MIM:608978] 383 405 zf-C2H2
23 UniProt Mutation Disease Start End Domain
P19544 R366C Denys-Drash syndrome (DDS) [MIM:194080] 353 377 zf-C2H2
P19544 R394W Denys-Drash syndrome (DDS) [MIM:194080] 383 405 zf-C2H2
P19544 R366L Denys-Drash syndrome (DDS) [MIM:194080] 353 377 zf-C2H2 Mitochondrial DNA depletion syndrome 1; MNGIE type P19971 G153S (MTDPS1) [MIM:603041] 109 340 Glycos_transf_3 Limb-girdle muscular dystrophy 2A (LGMD2A) P20807 G222R [MIM:253600] 75 415 Peptidase_C2 Limb-girdle muscular dystrophy 2A (LGMD2A) P20807 S606L [MIM:253600] 583 653 Calpain_u2 Maturity-onset diabetes of the young 3 (MODY3) P20823 S142F [MIM:600496] 8 168 HNF-1_N Maturity-onset diabetes of the young 3 (MODY3) P20823 H143Y [MIM:600496] 8 168 HNF-1_N Maturity-onset diabetes of the young 3 (MODY3) P20823 S594I [MIM:600496] 542 630 HNF-1A_C
P21333 P1291L FG syndrome 2 (FGS2) [MIM:300321] 1252 1346 Filamin Cholestasis; progressive familial intrahepatic; 3 (PFIC3) P21439 G535D [MIM:602347] 412 561 ABC_tran
P21817 R328W Malignant hyperthermia 1 (MHS1) [MIM:145600] 211 390 MIR
P21912 G53R Pheochromocytoma (PCC) [MIM:171300] 41 148 Fer2_3
P22033 P86L Methylmalonic aciduria type mut (MMAM) [MIM:251000] 62 574 MM_CoA_mutase
P22033 D625V Methylmalonic aciduria type mut (MMAM) [MIM:251000] 615 733 B12-binding
P22304 S143F Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
P22304 D198G Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
P22304 G140V Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
P22557 P520L Anemia; sideroblastic; 1 (SIDBA1) [MIM:300751] 189 536 Aminotran_1_2
P24752 G152A 3-ketothiolase deficiency (3KTD) [MIM:203750] 42 299 Thiolase_N
P25189 D224Y Charcot-Marie-Tooth disease 1B (CMT1B) [MIM:118200] 184 248 Myelin-PO_C Autoimmune lymphoproliferative syndrome 1A (ALPS1A) P25445 D260Y [MIM:601859] 230 314 Death Autoimmune lymphoproliferative syndrome 1A (ALPS1A) P25445 D260V [MIM:601859] 230 314 Death
P26439 E142K Adrenal hyperplasia 2 (AH2) [MIM:201810] 6 287 3Beta_HSD
P28062 G201V Nakajo syndrome (NKJO) [MIM:256040] 69 251 Proteasome X-linked immunodeficiency with hyper-IgM 1 (HIGM1) P29965 G257S [MIM:308230] 138 261 TNF X-linked immunodeficiency with hyper-IgM 1 (HIGM1) P29965 G257D [MIM:308230] 138 261 TNF
P30613 R385W Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200] 85 438 PK
P30613 G165V Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200] 85 438 PK
P30793 G83A Dystonia; dopa-responsive (DRD) [MIM:128230] 71 249 GTP_cyclohydroI
P31040 R589W Paragangliomas 5 (PGL5) [MIM:614165] 512 664 Succ_DH_flav_C Carbamoyl phosphate synthetase 1 deficiency (CPS1D) P31327 P1411L [MIM:237300] 1373 1465 MGS
P34059 G301C Mucopolysaccharidosis 4A (MPS4A) [MIM:253000] 31 355 Sulfatase
P35240 K579M Neurofibromatosis 2 (NF2) [MIM:101000] 347 595 ERM Epileptic encephalopathy; early infantile; 6 (EIEE6) P35498 S525F [MIM:607208] 503 718 Na_trans_cytopl Cystathionine beta-synthase deficiency (CBSD) P35520 P290L [MIM:236200] 80 376 PALP
P35575 P113L Glycogen storage disease 1A (GSD1A) [MIM:232200] 57 204 PAP2
P35575 H119L Glycogen storage disease 1A (GSD1A) [MIM:232200] 57 204 PAP2
P35579 R1165C Sebastian syndrome (SBS) [MIM:605249] 841 1921 Myosin_tail_1
24 UniProt Mutation Disease Start End Domain
P35579 R1165L Sebastian syndrome (SBS) [MIM:605249] 841 1921 Myosin_tail_1
P35579 R1165L May-Hegglin anomaly (MHA) [MIM:155100] 841 1921 Myosin_tail_1
P35579 D1424Y May-Hegglin anomaly (MHA) [MIM:155100] 841 1921 Myosin_tail_1
P35579 R1165C Fechtner syndrome (FTNS) [MIM:153640] 841 1921 Myosin_tail_1
P35579 R1165L Fechtner syndrome (FTNS) [MIM:153640] 841 1921 Myosin_tail_1
P35637 P431L Tremor; hereditary essential 4 (ETM4) [MIM:614782] 422 453 zf-RanBP
P35680 S148L Renal cysts and diabetes syndrome (RCAD) [MIM:137920] 8 174 HNF-1_N
P35680 S148W Renal cysts and diabetes syndrome (RCAD) [MIM:137920] 8 174 HNF-1_N
P35680 G285D Renal cysts and diabetes syndrome (RCAD) [MIM:137920] 232 307 Homeobox Neuronopathy; distal hereditary motor; 6 (HMN6) P38935 P216L [MIM:604320] 191 411 AAA_11
P40337 S65L Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 S65W Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 S68W Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 R200W Von Hippel-Lindau disease (VHLD) [MIM:193300] 149 204 VHL_C
P40337 S68W Pheochromocytoma (PCC) [MIM:171300] 63 144 VHL
P40337 R200W Erythrocytosis; familial; 2 (ECYT2) [MIM:263400] 149 204 VHL_C
P41250 G652A Charcot-Marie-Tooth disease 2D (CMT2D) [MIM:601472] 615 709 HGTP_anticodon Hereditary non-polyposis colorectal cancer 1 (HNPCC1) P43246 E562V [MIM:120435] 473 569 MutS_IV Cardiomyopathy; familial hypertrophic 2 (CMH2) P45379 R288C [MIM:115195] 234 296 Troponin Cardiomyopathy; familial hypertrophic 2 (CMH2) P45379 S189F [MIM:115195] 103 240 Troponin Cardiomyopathy; familial hypertrophic 2 (CMH2) P45379 N281I [MIM:115195] 234 296 Troponin Cardiomyopathy; familial hypertrophic 2 (CMH2) P45379 R140C [MIM:115195] 103 240 Troponin
P49747 D515G Pseudoachondroplasia (PSACH) [MIM:177170] 493 528 TSP_3
P50053 G40R Fructosuria (FRUCT) [MIM:229800] 3 294 PfkB
P50336 G358R Variegate porphyria (VP) [MIM:176200] 12 471 Amino_oxidase
P51531 D1158V Nicolaides-Baraitser syndrome (NCBRS) [MIM:601358] 1050 1164 Helicase_C
P51531 R1159L Nicolaides-Baraitser syndrome (NCBRS) [MIM:601358] 1050 1164 Helicase_C
P51608 R106W Rett syndrome (RTT) [MIM:312750] 91 162 MBD
P51648 G412R Sjoegren-Larsson syndrome (SLS) [MIM:270200] 2 424 Aldedh
P51648 H411Y Sjoegren-Larsson syndrome (SLS) [MIM:270200] 2 424 Aldedh Succinic semialdehyde dehydrogenase deficiency (SSADHD) P51649 P382L [MIM:271980] 69 530 Aldedh Succinic semialdehyde dehydrogenase deficiency (SSADHD) P51649 P382Q [MIM:271980] 69 530 Aldedh
P51687 S427Y Isolated sulfite oxidase deficiency (ISOD) [MIM:272300] 417 544 Mo-co_dimer
P51810 R5C Albinism ocular 1 (OA1) [MIM:300500] 1 396 Ocular_alb Microcephaly with or without chorioretinopathy; lymphedema; P52732 R944C or mental retardation (MCLMR) [MIM:152950] 916 1053 Microtub_bind Mitochondrial DNA depletion syndrome 9 (MTDPS9) P53597 G85A [MIM:245400] 53 146 CoA_binding Sensory ataxic neuropathy dysarthria and ophthalmoparesis P54098 H932Y (SANDO) [MIM:607459] 754 1185 DNA_pol_A Progressive external ophthalmoplegia with mitochondrial DNA P54098 H932Y deletions; autosomal recessive; 1 (PEOB1) [MIM:258450] 754 1185 DNA_pol_A Cutis laxa; autosomal recessive; 3A (ARCL3A) P54886 T299I [MIM:219150] 71 329 AA_kinase
25 UniProt Mutation Disease Start End Domain
P55017 R83W Gitelman syndrome (GTLMNS) [MIM:263800] 45 116 AA_permease_N
P55265 Y1112F Aicardi-Goutieres syndrome 6 (AGS6) [MIM:615010] 886 1215 A_deamin
P63267 P110L Visceral myopathy (VSCM) [MIM:155310] 3 376 Actin
P78363 A1038V Stargardt disease 1 (STGD1) [MIM:248200] 946 1090 ABC_tran
P78363 R1055W Stargardt disease 1 (STGD1) [MIM:248200] 946 1090 ABC_tran
P78363 A1038V Fundus flavimaculatus (FFM) [MIM:248200] 946 1090 ABC_tran
P78363 A1038V Cone-rod dystrophy 3 (CORD3) [MIM:604116] 946 1090 ABC_tran
P78504 G386R Alagille syndrome 1 (ALGS1) [MIM:118450] 378 408 EGF
P98161 P2471L Polycystic kidney disease 1 (PKD1) [MIM:173900] 2171 2614 REJ
P98161 T2083I Polycystic kidney disease 1 (PKD1) [MIM:173900] 2063 2135 PKD
P98161 Q3751R Polycystic kidney disease 1 (PKD1) [MIM:173900] 3711 4113 PKD_channel
P98172 T137A Craniofrontonasal syndrome (CFNS) [MIM:304110] 30 164 Ephrin
P98172 S138F Craniofrontonasal syndrome (CFNS) [MIM:304110] 30 164 Ephrin
P98194 P201L Hailey-Hailey disease (HHD) [MIM:169600] 133 328 E1-E2_ATPase Mitochondrial DNA depletion syndrome 15; hepatocerebral Q00059 P178L type (MTDPS15) [MIM:617156] 152 219 HMG_box_2
Q02846 R768W Leber congenital amaurosis 1 (LCA1) [MIM:204000] 554 805 Pkinase_Tyr
Q02846 R838C Cone-rod dystrophy 6 (CORD6) [MIM:601777] 808 865 HNOBA Radioulnar synostosis with amegakaryocytic Q03112 R750W thrombocytopenia 2 (RUSAT2) [MIM:616738] 733 755 zf-C2H2
Q03426 G202R Porokeratosis 3; multiple types (POROK3) [MIM:175900] 130 212 GHMP_kinases_N Hyperimmunoglobulinemia D and periodic fever syndrome Q03426 G202R (HIDS) [MIM:260920] 130 212 GHMP_kinases_N
Q05066 P125L 46;XY sex reversal 1 (SRXY1) [MIM:400044] 60 128 HMG_box
Q05066 Y127C 46;XY sex reversal 1 (SRXY1) [MIM:400044] 60 128 HMG_box
Q06124 Y279C Noonan syndrome 1 (NS1) [MIM:163950] 273 524 Y_phosphatase
Q06124 Y279C LEOPARD syndrome 1 (LPRD1) [MIM:151100] 273 524 Y_phosphatase
Q07837 G140R Cystinuria (CSNU) [MIM:220100] 140 491 Alpha-amylase
Q07889 Q477R Noonan syndrome 4 (NS4) [MIM:610733] 428 546 PH Mental retardation; autosomal dominant 9 (MRD9) Q12756 S215R [MIM:614255] 11 354 Kinesin
Q12809 S818L Long QT syndrome 2 (LQT2) [MIM:613688] 760 845 cNMP_binding
Q12824 R366C Coffin-Siris syndrome 3 (CSS3) [MIM:614608] 249 373 SNF5 Spastic paraplegia 10; autosomal dominant (SPG10) Q12840 S203C [MIM:604187] 17 327 Kinesin Epilepsy; focal; with speech disorder and with or without Q12879 I904F mental retardation (FESD) [MIM:245570] 839 1464 NMDAR2_C Epilepsy; focal; with speech disorder and with or without Q12879 D1251N mental retardation (FESD) [MIM:245570] 839 1464 NMDAR2_C Mental retardation; autosomal dominant 6 (MRD6) Q13224 R682C [MIM:613970] 555 829 Lig_chan
Q13402 G519D Usher syndrome 1B (USH1B) [MIM:276900] 67 729 Myosin_head
Q13402 G163R Usher syndrome 1B (USH1B) [MIM:276900] 67 729 Myosin_head
Q13501 P387L Paget disease of bone 3 (PDB3) [MIM:167250] 379 440 UBA_5 Frontotemporal dementia and/or amyotrophic lateral sclerosis Q13501 P387L 3 (FTDALS3) [MIM:616437] 379 440 UBA_5
Q13608 R812W Peroxisome biogenesis disorder 4A (PBD4A) [MIM:614862] 740 872 AAA
Q13950 R193C Cleidocranial dysplasia (CLCD) [MIM:119600] 102 231 Runt
26 UniProt Mutation Disease Start End Domain
Q13950 T220I Cleidocranial dysplasia (CLCD) [MIM:119600] 102 231 Runt
Q14524 G1740R Brugada syndrome 1 (BRGDA1) [MIM:601144] 1527 1783 Ion_trans
Q14683 R496C Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590] 3 1211 SMC_N Mental retardation; autosomal dominant 35 (MRD35) Q14738 P201R [MIM:616355] 103 513 B56
Q14896 P873L Left ventricular non-compaction 10 (LVNC10) [MIM:615396] 871 955 fn3 Cardiomyopathy; familial hypertrophic 4 (CMH4) Q14896 R733C [MIM:115197] 653 768 I-set
Q15465 G31R Holoprosencephaly 3 (HPE3) [MIM:142945] 24 184 HH_signal
Q15465 P424A Holoprosencephaly 3 (HPE3) [MIM:142945] 187 448 Hint
Q15465 G196E Holoprosencephaly 3 (HPE3) [MIM:142945] 187 448 Hint
Q15465 S280W Holoprosencephaly 3 (HPE3) [MIM:142945] 187 448 Hint
Q15526 G257R Leigh syndrome (LS) [MIM:256000] 67 283 SURF1 Limb-girdle muscular dystrophy 2D (LGMD2D) Q16586 G91R [MIM:608099] 7 382 Sarcoglycan_2
Q5HYA8 G821R Nephronophthisis 11 (NPHP11) [MIM:613550] 167 995 Meckelin
Q5HYA8 G821S Nephronophthisis 11 (NPHP11) [MIM:613550] 167 995 Meckelin Combined oxidative phosphorylation deficiency 20 Q5ST30 T337I (COXPD20) [MIM:615917] 112 735 tRNA-synt_1
Q6PJF5 P189L Tylosis with esophageal cancer (TOC) [MIM:148500] 128 334 Rhomboid_SP Ichthyosis; congenital; autosomal recessive 4A (ARCI4A) Q86UK0 G1381E [MIM:601277] 1361 1507 ABC_tran
Q8IVH4 R209S Methylmalonic aciduria type cblA (MMAA) [MIM:251100] 101 384 ArgK Persistent hyperplastic primary vitreous; autosomal recessive Q8N100 E49V (PHPVAR) [MIM:221900] 41 93 HLH
Q8N653 R284C Noonan syndrome 10 (NS10) [MIM:616564] 283 328 Kelch_1
Q8NFG4 S108I Birt-Hogg-Dube syndrome (BHD) [MIM:135150] 104 265 Folliculin
Q8WVJ9 E75A Barber-Say syndrome (BBRSAY) [MIM:209885] 67 118 HLH Emery-Dreifuss muscular dystrophy 5; autosomal dominant Q8WXH0 T6211M (EDMD5) [MIM:612999] 6136 6242 Spectrin
Q93099 P359L Alkaptonuria (AKU) [MIM:203500] 5 434 HgmA
Q93099 P373L Alkaptonuria (AKU) [MIM:203500] 5 434 HgmA
Q96CV9 H486R Glaucoma 1; open angle; E (GLC1E) [MIM:137760] 408 507 CC2-LZ 3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D) Q96RQ3 A289V [MIM:210200] 163 371 CPSase_L_D2 3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D) Q96RQ3 R232W [MIM:210200] 163 371 CPSase_L_D2 3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D) Q96RQ3 G209V [MIM:210200] 163 371 CPSase_L_D2
Q99519 Y370C Sialidosis (SIALIDOSIS) [MIM:256550] 88 381 BNR_2
Q99593 R237W Holt-Oram syndrome (HOS) [MIM:142900] 56 238 T-box
Q99708 R100W Seckel syndrome 2 (SCKL2) [MIM:606744] 20 139 CtIP_N
Q99814 M535V Erythrocytosis; familial; 4 (ECYT4) [MIM:611783] 517 549 HIF-1
Q99895 G32V Pancreatitis; hereditary (PCTT) [MIM:167800] 30 262 Trypsin
Q9BYB0 P141A Phelan-McDermid syndrome (PHMDS) [MIM:606232] 119 213 Ank_2 Epileptic encephalopathy; early infantile; 44 (EIEE44) Q9GZZ9 G168E [MIM:617132] 53 310 ThiF
Q9H251 D2376V Usher syndrome 1D (USH1D) [MIM:601067] 2301 2393 Cadherin
Q9H444 D129V Cataract 31; multiple types (CTRCT31) [MIM:605387] 24 199 Snf7 Neuropathy; hereditary sensory and autonomic; 8 (HSAN8) Q9H4Q4 H289L [MIM:616488] 271 293 zf-C2H2
27 UniProt Mutation Disease Start End Domain Hypotonia; ataxia; and delayed development syndrome Q9H4W6 G171D (HADDS) [MIM:617330] 17 247 COE1_DBD
Q9H9D4 H455Y Vitreoretinopathy; exudative 6 (EVR6) [MIM:616468] 437 459 zf-C2H2 3-methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D) Q9HCC0 G517R [MIM:210210] 74 558 Carboxyl_trans
Q9NP59 D270V Hemochromatosis 4 (HFE4) [MIM:606069] 22 531 FPN1 Dyskeratosis congenita; autosomal recessive; 1 (DKCB1) Q9NPE3 R34W [MIM:224230] 3 52 Nop10p
Q9NVV9 S6F Dystonia 6; torsion (DYT6) [MIM:602629] 5 81 THAP
Q9NVV9 S6P Dystonia 6; torsion (DYT6) [MIM:602629] 5 81 THAP
Q9NZR4 R166W Keratoconus 1 (KTCN1) [MIM:148300] 165 221 Homeobox
Q9P2K1 T1114M Meckel syndrome 6 (MKS6) [MIM:612284] 1041 1205 C2
Q9P2K1 T1114M Joubert syndrome 9 (JBTS9) [MIM:612285] 1041 1205 C2
Q9UBX1 S480L Ceroid lipofuscinosis; neuronal; 13 (CLN13) [MIM:615362] 271 482 Peptidase_C1
Q9ULV0 G168R Diarrhea 2; with microvillus atrophy (DIAR2) [MIM:251850] 71 749 Myosin_head Cerebral arteriopathy; autosomal dominant; with subcortical infarcts and leukoencephalopathy; 1 (CADASIL1) Q9UM47 G171C [MIM:125310] 158 201 EGF_CA Cerebral arteriopathy; autosomal dominant; with subcortical infarcts and leukoencephalopathy; 1 (CADASIL1) Q9UM47 G149C [MIM:125310] 123 154 EGF Cerebral arteriopathy; autosomal dominant; with subcortical infarcts and leukoencephalopathy; 1 (CADASIL1) Q9UM47 R207C [MIM:125310] 201 232 EGF Spastic paraplegia 7; autosomal recessive (SPG7) Q9UQ90 S692T [MIM:607259] 541 746 Peptidase_M41 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus Q9Y243 R465W syndrome 2 (MPPH2) [MIM:615937] 426 473 Pkinase_C
Q9Y5X4 G56R Retinitis pigmentosa 37 (RP37) [MIM:611131] 45 115 zf-C4
Q9Y6X9 S87L Charcot-Marie-Tooth disease 2Z (CMT2Z) [MIM:616688] 26 169 HATPase_c_3
Non-diseasse mutation
A2VEC9 R3273W - 3256 3306 TSP_1
A2VEC9 S4028I - 4008 4058 TSP_1
A4D0S4 G1028C - 1022 1077 Laminin_EGF
A6NGG8 R258I - 1 1264 Retinal
A6NLF2 P375L - 352 450 Elongin_A
A8MWS1 E258D - 227 306 ig
O00115 R314L - 18 347 DNase_II
O00311 T472I - 358 482 Pkinase
O00533 T287A - 234 314 Ig_3
O00748 R34W - 30 538 COesterase
O14558 P20L - 3 62 Crystallin
O15146 P696L - 575 856 Pkinase_Tyr
O15197 S324A - 304 346 Ephrin_rec_like
O15197 S332L - 304 346 Ephrin_rec_like
O15255 S152W - 1 209 CAAX_1
O15371 R310C - 4 521 eIF-3_zeta
O43157 R389W - 37 460 Sema
O43272 R185W - 183 577 Pro_dh
28 UniProt Mutation Disease Start End Domain
O43316 R191C - 171 227 Homeobox
O43316 R200H - 171 227 Homeobox
O43683 G20D - 6 126 Mad3_BUB1_I
O60240 P194A - 14 397 Perilipin
O60318 S102L - 2 291 NupH_GANP
O60333 T873I - 845 892 KIF1B
O60494 G1840S - 1738 1847 CUB
O60934 Q216K - 216 325 NIBRIN_BRCT_II
O75022 H405Y - 324 418 Ig_2
O75095 G1137A - 1132 1174 Laminin_EGF
O75106 P141L - 62 148 Cu_amine_oxidN2
O75306 P352A - 193 463 Complex1_49kDa
O75309 L191F - 131 234 Cadherin
O75521 M47I - 40 120 ACBP
O75716 R266W - 20 290 Pkinase
O75716 P277L - 20 290 Pkinase
O75828 M235L - 184 243 adh_short
O75923 R253W - 220 323 C2
O75969 S700F - 166 853 AKAP_110
O94856 T159M - 146 222 ig
O94901 A203V - 62 318 MRP
O95050 R258H - 1 259 NNMT_PNMT_TEMT
O95382 R499C - 129 507 DUF4071
O95393 N250K - 52 256 TGFb_propeptide
O95704 G165R - 119 257 PID
O95786 R7C - 1 93 CARD_2
O95925 K128T - 76 128 Kunitz_BPTI
P00747 R408W - 377 454 Kringle
P00747 A494V - 481 560 Kringle
P00747 R523W - 481 560 Kringle
P00750 R164W - 127 208 Kringle
P01889 D98Y - 25 203 MHC_I
P01891 Q94H - 25 203 MHC_I
P01891 T97I - 25 203 MHC_I
P01909 P44L - 29 108 MHC_II_alpha
P02549 S109F - 53 156 Spectrin
P02647 P167R - 69 262 Apolipoprotein
P02647 E171V - 69 262 Apolipoprotein
P02649 R246C - 81 292 Apolipoprotein
P02675 N170H - 91 234 Fib_alpha
P02708 D383V - 263 403 Neur_chan_memb
29 UniProt Mutation Disease Start End Domain
P02724 E76K - 34 146 Glycophorin_A
P02724 T77I - 34 146 Glycophorin_A
P02748 D127Y - 99 134 Ldl_recept_a
P04114 P554L - 46 598 Vitellogenin_N
P04440 G114E - 42 114 MHC_II_beta
P04440 G113V - 42 114 MHC_II_beta
P04440 G113D - 42 114 MHC_II_beta
P05120 S413C - 6 415 Serpin
P05177 G299S - 42 505 p450
P05177 S298R - 42 505 p450
P05177 P42R - 42 505 p450
P06132 P106L - 14 360 URO-D
P06401 P186L - 1 564 Prog_receptor
P06756 S548A - 467 914 Integrin_alpha2
P07307 G85R - 29 167 Lectin_N
P07498 R110L - 21 181 Casein_kappa
P08183 S893A - 711 986 ABC_membrane
P08183 S893T - 711 986 ABC_membrane
P08567 R5W - 5 101 PH
P08603 S890I - 870 926 Sushi
P08686 G375S - 27 480 p450
P08729 G364A - 90 402 Filament
P08908 G273D - 53 400 7tm_1
P09237 P241L - 103 259 Peptidase_M10
P09619 N718Y - 600 958 Pkinase_Tyr
P09651 N73S - 16 85 RRM_1
P09848 S190L - 74 225 Glyco_hydro_1
P09874 K940R - 808 1007 PARP
P09923 H298L - 52 487 Alk_phosphatase
P0CB38 S331N - 295 363 RRM_1
P0DMM9 P101L - 38 288 Sulfotransfer_1
P0DMN0 P101L - 38 288 Sulfotransfer_1
P10072 T628I - 607 629 zf-C2H2
P10316 Q94H - 25 203 MHC_I
P10321 S123Y - 25 203 MHC_I
P10321 E201K - 25 203 MHC_I
P10321 A348V - 338 365 MHC_I_C
P10321 L171W - 25 203 MHC_I
P10321 S123C - 25 203 MHC_I
P10321 S123F - 25 203 MHC_I
P10515 S98F - 92 165 Biotin_lipoyl
30 UniProt Mutation Disease Start End Domain
P10635 P469A - 34 494 p450
P10636 V617I - 592 622 Tubulin-binding
P10909 N317H - 30 447 Clusterin
P11055 R1137C - 844 1925 Myosin_tail_1
P11055 A1003V - 844 1925 Myosin_tail_1
P11215 A858V - 614 1005 Integrin_alpha2
P11226 N214Y - 144 246 Lectin_C
P11712 G417D - 30 487 p450
P12018 S122L - 24 132 V-set
P12110 G935R - 833 1010 VWA
P12882 R1341C - 847 1928 Myosin_tail_1
P12882 R1716C - 847 1928 Myosin_tail_1
P12883 R1475C - 843 1924 Myosin_tail_1
P13533 E1295Q - 845 1926 Myosin_tail_1
P13535 A636V - 90 769 Myosin_head
P13646 T298A - 103 415 Filament
P13942 P1722L - 1616 1734 COLFI
P14618 G204V - 42 395 PK
P14679 P313R - 170 403 Tyrosinase
P15538 A348T - 42 498 p450
P15814 P120L - 116 201 C1-set
P16109 S619A - 572 629 Sushi
P17097 S347L - 334 356 zf-C2H2
P18887 R7L - 1 149 XRCC1_N
P19793 P261L - 257 442 Hormone_recep
P19878 R395W - 351 429 PB1
P20813 S259R - 31 488 p450
P21333 S1012L - 968 1058 Filamin
P21709 R351C - 334 431 fn3
P22102 P641A - 606 777 AIRS_C
P22735 S755L - 691 788 Transglut_C
P22894 D193V - 107 262 Peptidase_M10
P22897 G396S - 380 488 Lectin_C
P23468 R995C - 920 1006 fn3
P24821 D850H - 804 884 fn3
P28566 S262F - 39 344 7tm_1
P29965 G219R - 138 261 TNF
P30048 T234I - 218 253 1-cysPrx_C
P30291 S472I - 299 569 Pkinase
P30443 D114A - 25 203 MHC_I
P30453 R121I - 25 203 MHC_I
31 UniProt Mutation Disease Start End Domain
P30460 D98Y - 25 203 MHC_I
P30462 D98Y - 25 203 MHC_I
P30464 S91C - 25 203 MHC_I
P30464 S91Y - 25 203 MHC_I
P30466 S91F - 25 203 MHC_I
P30475 D98Y - 25 203 MHC_I
P30480 D98Y - 25 203 MHC_I
P30492 T97A - 25 203 MHC_I
P30492 D98Y - 25 203 MHC_I
P30493 T97A - 25 203 MHC_I
P30493 D98Y - 25 203 MHC_I
P30495 T97A - 25 203 MHC_I
P30495 D98Y - 25 203 MHC_I
P30498 D98Y - 25 203 MHC_I
P30499 N92K - 25 203 MHC_I
P30499 S202T - 25 203 MHC_I
P30501 N92K - 25 203 MHC_I
P30511 P71Q - 22 200 MHC_I
P30685 G40V - 25 203 MHC_I
P31151 E28D - 6 45 S_100
P34130 S89N - 89 208 NGF
P34810 A350T - 37 354 Lamp
P35318 S50R - 1 151 Calc_CGRP_IAPP
P35613 G269V - 220 305 Ig_3
P37088 R181W - 62 572 ASC
P37173 M373I - 244 538 Pkinase_Tyr
P40199 G239V - 239 318 Ig_2
P40692 R755W - 502 756 Mlh1_C
P40692 P309S - 216 335 DNA_mis_repair
P43403 R175L - 163 239 SH2
P43626 P135L - 132 213 ig
P45379 N279Y - 234 296 Troponin
P48448 S302R - 3 347 Aldedh
P48552 S803L - 753 840 NRIP1_repr_3
P49454 R300C - 1 307 CENP-F_N
P49454 Q250L - 1 307 CENP-F_N
P49643 Q265L - 182 448 DNA_primase_lrg
P49643 G259S - 182 448 DNA_primase_lrg
P49747 R381C - 360 395 TSP_3
P49755 S64Y - 31 213 EMP24_GP25L
P49790 P821L - 793 822 zf-RanBP
32 UniProt Mutation Disease Start End Domain
P49790 V381F - 113 621 Nup153
P49802 Q409H - 333 447 RGS
P50479 V184I - 146 229 DUF4749
P50748 P1830L - 1580 2129 Rod_C
P50895 V196I - 150 248 C2-set_2
P51511 G609R - 602 669 DUF3377
P51531 G1416A - 1411 1493 Bromodomain
P51957 P225A - 6 261 Pkinase
P51957 P250L - 6 261 Pkinase
P51993 P124S - 59 169 Glyco_tran_10_N
P52742 S507L - 494 516 zf-C2H2
P52742 G579R - 578 600 zf-C2H2
P54886 S372Y - 355 658 Aldedh
P55317 G72A - 17 169 Forkhead_N
P55327 D52Y - 49 210 TPD52
P57078 N562Y - 533 615 Ank_2
P59282 R133L - 6 161 p25-alpha
P62195 R258W - 186 319 AAA
P69905 D7V - 7 107 Globin
P69905 D7Y - 7 107 Globin
P69905 G52D - 7 107 Globin
P69905 G52R - 7 107 Globin
P69905 G58R - 7 107 Globin
P69905 H59Y - 7 107 Globin
P69905 G60D - 7 107 Globin
P69905 G60V - 7 107 Globin
P78324 Q261L - 256 338 C1-set
P98155 P262H - 237 273 Ldl_recept_a
P98161 P1786L - 1723 1792 PKD
Q02246 R657W - 609 697 fn3
Q02833 P89A - 6 89 RA
Q02846 A328V - 72 400 ANF_receptor
Q04826 S91F - 25 203 MHC_I
Q04912 G356D - 61 504 Sema
Q05823 S406F - 369 523 Pkinase
Q07889 P655L - 600 717 RasGEF_N
Q0P670 S108A - 1 258 Spem1
Q0VG06 P660L - 449 881 FANCAA
Q12872 L122F - 34 156 DRY_EERY
Q12931 E572K - 287 704 HSP90
Q13045 R1243H - 1177 1255 Gelsolin
33 UniProt Mutation Disease Start End Domain
Q13111 D167V - 1 226 CAF1-p150_N
Q13308 P1029T - 796 1061 Pkinase_Tyr
Q13315 R45W - 8 165 TAN
Q13351 H299Y - 279 303 zf-C2H2
Q13387 P743L - 683 814 PID
Q13469 H446R - 410 570 RHD_DNA_bind
Q13488 P161L - 27 825 V_ATPase_I
Q13564 S101F - 13 533 ThiF
Q13576 R1379W - 1367 1498 RasGAP_C
Q13596 S115Y - 10 138 Sorting_nexin
Q13740 G229D - 137 231 C2-set_2
Q13936 P1868L - 1701 1996 CAC1F_C
Q13936 R1972C - 1701 1996 CAC1F_C
Q14524 P656L - 478 667 Na_trans_cytopl
Q14896 R1002W - 975 1062 I-set
Q15154 T1543I - 1372 1998 PCM1_C
Q15413 Y693C - 659 794 SPRY
Q15772 R1234W - 1188 1277 I-set
Q16696 R257C - 34 491 p450
Q17RF5 P30L - 25 129 DUF4721
Q17RS7 S92T - 1 96 XPG_N
Q29718 T97A - 25 203 MHC_I
Q29718 D98Y - 25 203 MHC_I
Q29836 T97A - 25 203 MHC_I
Q29836 D98Y - 25 203 MHC_I
Q29980 P68H - 24 201 MHC_I
Q29980 D75N - 24 201 MHC_I
Q29983 M152V - 24 200 MHC_I
Q2M2I3 T91A - 16 290 DUF1669
Q31610 D98Y - 25 203 MHC_I
Q3BBV0 Q850K - 806 868 DUF1220
Q3KQV3 R525W - 506 528 zf-C2H2
Q3MIN7 R615C - 613 700 RA
Q3SYG4 T549I - 441 819 PHTB1_C
Q4L235 P93R - 7 450 AMP-binding
Q4LDR2 E17V - 6 81 Cortexin
Q52LG2 R26C - 1 170 PMG
Q53HC0 S70C - 24 80 CCDC92
Q5IJ48 T1110M - 1103 1124 hEGF
Q5SSQ6 P99L - 35 114 Suppressor_APC
Q5SZK8 R1840W - 1762 1858 Calx-beta
34 UniProt Mutation Disease Start End Domain
Q5T4S7 M4867L - 4367 5163 E3_UbLigase_R4
Q5TAP6 T101A - 22 734 Utp14
Q6GTS8 S258C - 121 488 Peptidase_M20
Q6IAA8 S73L - 16 85 LAMTOR
Q6IQ23 A248V - 165 282 PH
Q6N021 M1701I - 1290 1905 Tet_JBP
Q6PEW1 R7C - 3 213 PNMA
Q6UB98 P277A - 250 282 Ank
Q6UWM7 T212M - 33 503 Glyco_hydro_1
Q6UWY2 P143L - 34 258 Trypsin
Q6UXK2 S137F - 123 183 LRR_8
Q6UY09 S355L - 351 420 Ig_3
Q6V0I7 S3873N - 3862 3898 EGF_CA
Q6WRI0 H2579Y - 2527 2609 Ig_3
Q6ZNL6 E941K - 896 1082 RhoGEF
Q6ZRI0 P1129L - 986 1132 VWD
Q6ZUB1 A736V - 420 789 FAM75
Q6ZVW7 G70R - 25 298 IL17_R_N
Q6ZWJ8 P1128R - 1086 1143 VWC
Q6ZWL3 E275K - 51 517 p450
Q75MW2 H31R - 11 81 DUF3669
Q7Z2Z1 R402W - 208 1004 Treslin_N
Q7Z3Z2 R47C - 5 133 RD3
Q86T90 R383C - 93 410 KIAA1328
Q86TY3 T96I - 28 610 DUF4696
Q86VI3 P1097S - 1009 1221 RasGAP
Q86W24 N48T - 14 89 PYRIN
Q86YC2 G998E - 837 1184 PALB2_WD40
Q86YW0 S500L - 482 588 C2
Q8IUB2 H36D - 29 68 WAP
Q8IV08 P297L - 226 403 PLDc_3
Q8IVF6 N484S - 327 618 CCDC144C
Q8IVV2 G348C - 277 393 PLAT
Q8IWL2 R219W - 144 248 Lectin_C
Q8IWZ3 G228C - 209 302 Ank_2
Q8IYS4 R302C - 21 520 DUF4701
Q8IYX3 R96C - 18 404 DUF4702
Q8IZ63 P118L - 63 422 PRR22
Q8N0Y7 R40C - 6 138 His_Phos_1
Q8N0Z8 R197W - 168 285 PseudoU_synth_1
Q8N126 R162W - 133 220 C2-set_2
35 UniProt Mutation Disease Start End Domain
Q8N149 R381C - 327 409 ig
Q8N1F7 S509R - 214 804 Nic96
Q8N1H7 S309L - 31 587 S6OS1
Q8N2C7 R131W - 16 236 UNC80
Q8N387 T202I - 20 334 Mucin15
Q8N4N8 P417S - 219 543 Kinesin
Q8N715 R380L - 251 620 DUF4659
Q8N7Q3 S292W - 281 303 zf-C2H2
Q8N865 R86C - 1 283 DUF4555
Q8N8J6 T360I - 344 366 zf-C2H2
Q8NAC3 S182L - 142 530 IL17_R_N
Q8NAG6 A71V - 11 106 Ank_2
Q8NEM0 R304I - 225 607 Microcephalin
Q8NEM7 M154V - 61 161 Spt20
Q8NFD5 D1987Y - 1927 2182 BAF250_C
Q8NFW9 P365L - 152 859 Rab_eff_C
Q8NG06 T374M - 345 454 SPRY
Q8NGD0 G232D - 31 307 7tm_4
Q8NGJ6 R311W - 33 311 7tm_4
Q8TBA6 M486V - 420 725 Golgin_A5
Q8TD31 S164R - 27 773 HCR
Q8TD31 R417W - 27 773 HCR
Q8TD31 K546R - 27 773 HCR
Q8TD31 G575C - 27 773 HCR
Q8TDN1 G325R - 220 464 Ion_trans
Q8TDR0 M620L - 49 685 MIP-T3
Q8TE60 S1159T - 1129 1177 TSP_1
Q8TEU7 S570A - 530 609 PDZ
Q8WVK2 S114F - 1 151 DUF1777
Q8WW52 G546D - 338 575 DUF2181
Q8WWU5 G253A - 58 487 Tcp11
Q8WXD2 M233V - 17 468 SGIII
Q8WZ42 K16067I - 16036 16120 I-set
Q92543 L618F - 532 659 PX
Q92614 A958V - 407 1062 Myosin_head
Q92665 T241M - 96 389 MRP-S31
Q92826 R217C - 217 273 Homeobox
Q93033 G157S - 151 267 V-set
Q95365 N87K - 25 203 MHC_I
Q96BD8 V91I - 16 248 SKA1
Q96E22 N175Y - 156 292 Prenyltransf
36 UniProt Mutation Disease Start End Domain
Q96FF9 S156Y - 89 215 Sororin
Q96H86 A332V - 315 337 zf-C2H2
Q96LB9 G126S - 47 181 Amidase_2
Q96LP6 P182R - 96 359 DUF4607
Q96PP9 M542I - 298 594 GBP_C
Q96PP9 M545I - 298 594 GBP_C
Q96PP9 M545L - 298 594 GBP_C
Q96PQ1 A82V - 27 142 V-set
Q96RD9 N427K - 379 466 Ig_2
Q96RP7 A467V - 277 469 Gal-3-0_sulfotr
Q99453 R100L - 99 155 Homeobox
Q99466 P204L - 194 238 EGF_CA
Q99466 P206L - 194 238 EGF_CA
Q99466 S244L - 238 272 EGF
Q99575 S127L - 107 191 POP1
Q99593 P132S - 56 238 T-box
Q99640 R140C - 110 359 Pkinase
Q99706 P209A - 129 209 ig
Q9BPW4 S326L - 46 348 ApoL
Q9BSK1 R346C - 326 348 zf-C2H2
Q9BW71 A496V - 485 518 CHZ
Q9BWW9 T323M - 44 350 ApoL
Q9BWX5 S19W - 1 176 GATA-N
Q9BXB7 G147E - 5 567 NYD-SP12_N
Q9BXI9 P119L - 76 122 Collagen
Q9BXM7 S477T - 264 509 Pkinase
Q9BXR5 R799L - 633 802 TIR
Q9BXW9 P714L - 1 1415 FancD2
Q9BYK8 S788N - 712 916 AAA_12
Q9C019 S324N - 296 344 PRY
Q9GZR1 A820V - 680 845 Peptidase_C48
Q9GZW5 P110T - 41 130 SCAN
Q9H0A9 P113L - 1 153 Speriolin_N
Q9H171 R17I - 11 69 z-alpha
Q9H251 P2380L - 2301 2393 Cadherin
Q9H2R5 P134L - 22 249 Trypsin
Q9H2X9 P1100L - 1032 1139 SLC12
Q9H4K1 R180C - 1 309 RIB43A
Q9H4K7 H93R - 73 223 GTP1_OBG
Q9H568 R245C - 2 366 Actin
Q9H8X2 R277W - 13 457 Ins_P5_2-kin
37 UniProt Mutation Disease Start End Domain
Q9H8Y5 R569W - 531 575 Ank_5
Q9H9F9 R298L - 280 570 Actin
Q9HBH7 A40V - 2 121 BEX
Q9HBH7 M66I - 2 121 BEX
Q9HCM1 S1208C - 669 1737 DUF4617
Q9NP94 H154Y - 5 306 Zip
Q9NP95 P175A - 65 191 FGF
Q9NQE7 S104I - 64 494 Peptidase_S28
Q9NSE7 S228N - 118 228 ABC_membrane
Q9NSI2 V212L - 99 221 SLX9
Q9NV72 R521C - 504 526 zf-C2H2
Q9NVX2 S434N - 404 442 WD40
Q9NXF7 N45S - 1 216 DCA16
Q9NXF7 T129I - 1 216 DCA16
Q9NY87 V59F - 1 94 SPAN-X
Q9NYQ6 S664W - 570 678 Cadherin
Q9NZ94 S92Y - 40 624 COesterase
Q9NZL3 H506D - 484 506 zf-C2H2
Q9NZP6 P343A - 154 383 POM121
Q9NZR1 P63A - 5 146 Tropomodulin
Q9P0K1 P81R - 36 188 Pep_M12B_propep
Q9P0L0 P104L - 14 120 Motile_Sperm
Q9P0W8 G324E - 9 422 HSD3
Q9P2E3 T910A - 864 1040 AAA_11
Q9P2H0 G238C - 105 1081 K1377
Q9UBL3 S478F - 420 498 SPRY
Q9UBV4 T263I - 49 365 wnt
Q9UGM3 H1084Y - 996 1093 SRCR
Q9UHF1 G114R - 102 134 EGF_2
Q9UHK6 M261I - 3 350 CoA_transf_3
Q9UK13 S519T - 506 528 zf-C2H2
Q9UK80 G321D - 212 555 UCH
Q9UKN7 T2205I - 2108 2216 MyTH4
Q9UKP4 G1583A - 1574 1628 TSP_1
Q9UKR3 H109Y - 36 258 Trypsin
Q9UKW4 Q618H - 596 658 SH3_2
Q9UKX3 H1862R - 847 1928 Myosin_tail_1
Q9ULS5 P232Q - 65 465 Tmemb_cc2
Q9UM07 T79M - 1 111 PAD_N
Q9UN88 F478I - 272 579 Neur_chan_memb
Q9Y2V7 H300Y - 56 656 COG6
38 UniProt Mutation Disease Start End Domain
Q9Y2X0 L770F - 119 829 Med16
Q9Y4G6 V1877I - 1850 1974 VBS
Q9Y572 E260V - 21 283 Pkinase
Q9Y5G0 G188S - 138 233 Cadherin
Q9Y5Z7 G268A - 254 323 Kelch_3
39 Table S8. Pfam domain mapping results for OD disease and non-disease mutations
UniProt Mutation Disease Start End Domain
Disease mutation
A2RRP1 L1055P Infantile liver failure syndrome 2 (ILFS2) [MIM:616483] 726 1376 Sec39
A6NCS4 F151L Conotruncal heart malformations (CTHM) [MIM:217095] 133 189 Homeobox
A6NCS4 K152Q Conotruncal heart malformations (CTHM) [MIM:217095] 133 189 Homeobox Familial multiple endocrine neoplasia type I (MEN1) O00255 L291P [MIM:131100] 1 516 Menin
O00294 F382S Retinitis pigmentosa 14 (RP14) [MIM:600132] 297 537 Tub
O00571 R475G Mental retardation; X-linked 102 (MRX102) [MIM:300958] 426 536 Helicase_C
O00754 L809P Mannosidosis; alpha B; lysosomal (MANSA) [MIM:248500] 510 1001 Glyco_hydro_38C
O14896 W60G Popliteal pterygium syndrome (PPS) [MIM:119500] 9 114 IRF
O15118 N222S Niemann-Pick disease C1 (NPC1) [MIM:257220] 22 267 NPC1_N
O15118 V231G Niemann-Pick disease C1 (NPC1) [MIM:257220] 22 267 NPC1_N
O15232 V194D Multiple epiphyseal dysplasia 5 (EDM5) [MIM:607078] 83 257 VWA
O15232 I192N Multiple epiphyseal dysplasia 5 (EDM5) [MIM:607078] 83 257 VWA Night blindness; congenital stationary; 1B (CSNB1B) O15303 C522Y [MIM:257270] 514 564 NCD3G
O15305 I132T Congenital disorder of glycosylation 1A (CDG1A) [MIM:212065] 28 246 PMM
O15305 Y229S Congenital disorder of glycosylation 1A (CDG1A) [MIM:212065] 28 246 PMM
O15305 I132N Congenital disorder of glycosylation 1A (CDG1A) [MIM:212065] 28 246 PMM
O15305 C241S Congenital disorder of glycosylation 1A (CDG1A) [MIM:212065] 28 246 PMM
O15528 R389G Rickets vitamin D-dependent 1A (VDDR1A) [MIM:264700] 41 505 p450
O15528 V478G Rickets vitamin D-dependent 1A (VDDR1A) [MIM:264700] 41 505 p450 Immunodeficiency-centromeric instability-facial anomalies O43167 C408G syndrome 2 (ICF2) [MIM:614069] 407 428 zf-C2H2
O43405 I109N Deafness; autosomal dominant; 9 (DFNA9) [MIM:601369] 32 121 LCCL
O43405 W117R Deafness; autosomal dominant; 9 (DFNA9) [MIM:601369] 32 121 LCCL
O60216 C585R Cornelia de Lange syndrome 4 (CDLS4) [MIM:614701] 574 628 Rad21_Rec8
O60260 T415N Parkinson disease 2 (PARK2) [MIM:600116] 399 458 IBR
O60260 C418R Parkinson disease 2 (PARK2) [MIM:600116] 399 458 IBR
O60313 I382M Optic atrophy 1 (OPA1) [MIM:165500] 291 469 Dynamin_N
O60313 T330S Optic atrophy 1 (OPA1) [MIM:165500] 291 469 Dynamin_N
O60313 I382M Behr syndrome (BEHRS) [MIM:210000] 291 469 Dynamin_N
O60500 R586G Nephrotic syndrome 1 (NPHS1) [MIM:256300] 548 634 C2-set_2
O60663 A236P Nail-patella syndrome (NPS) [MIM:161200] 220 276 Homeobox
O60663 L252P Nail-patella syndrome (NPS) [MIM:161200] 220 276 Homeobox
O75096 D137N Cenani-Lenz syndactyly syndrome (CLSS) [MIM:212780] 108 143 Ldl_recept_a Pituitary hormone deficiency; combined; 2 (CPHD2) O75360 F88S [MIM:262600] 70 126 Homeobox
O75369 L1431R Larsen syndrome (LRS) [MIM:150250] 1418 1508 Filamin
O75369 S188P Atelosteogenesis 1 (AO1) [MIM:108720] 139 243 CH Mental retardation; autosomal dominant 24 (MRD24) O75398 I228S [MIM:615828] 197 272 SAND
O75443 F211S Deafness; autosomal dominant; 12 (DFNA12) [MIM:601543] 163 251 NIDO
40 UniProt Mutation Disease Start End Domain
O75443 D1136H Deafness; autosomal dominant; 12 (DFNA12) [MIM:601543] 1100 1258 VWD
O75445 R303S Usher syndrome 2A (USH2A) [MIM:276901] 292 516 Laminin_N
O75923 V67D Miyoshi muscular dystrophy 1 (MMD1) [MIM:254130] 1 103 C2
O75923 V67D Limb-girdle muscular dystrophy 2B (LGMD2B) [MIM:253601] 1 103 C2
O95140 W740S Charcot-Marie-Tooth disease 2A2A (CMT2A2A) [MIM:609260] 594 754 Fzo_mitofusin
O95255 A1303P Pseudoxanthoma elasticum (PXE) [MIM:264800] 1282 1430 ABC_tran
O95255 S398G Pseudoxanthoma elasticum (PXE) [MIM:264800] 311 581 ABC_membrane
O95278 W32G Epilepsy; progressive myoclonic 2 (EPM2) [MIM:254780] 12 117 CBM_20
O95343 V92G Holoprosencephaly 2 (HPE2) [MIM:157170] 87 201 SIX1_SD
O95343 A93D Holoprosencephaly 2 (HPE2) [MIM:157170] 87 201 SIX1_SD
O95394 L83S Immunodeficiency 23 (IMD23) [MIM:615816] 44 102 PGM_PMM_I
O95409 T403K Holoprosencephaly 5 (HPE5) [MIM:609637] 393 415 zf-C2H2
P00439 I65N Phenylketonuria (PKU) [MIM:261600] 35 100 ACT
P00439 I65T Phenylketonuria (PKU) [MIM:261600] 35 100 ACT
P00439 Y277D Phenylketonuria (PKU) [MIM:261600] 119 449 Biopterin_H
P00439 I65S Phenylketonuria (PKU) [MIM:261600] 35 100 ACT
P00439 I65V Phenylketonuria (PKU) [MIM:261600] 35 100 ACT
P00439 I65V Hyperphenylalaninemia (HPA) [MIM:261600] 35 100 ACT
P00441 V149G Amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400] 9 150 Sod_Cu
P00441 L145S Amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400] 9 150 Sod_Cu
P00441 C147R Amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400] 9 150 Sod_Cu
P00441 T55R Amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400] 9 150 Sod_Cu
P00451 C348R Hemophilia A (HEMA) [MIM:306700] 218 349 Cu-oxidase
P00451 C348S Hemophilia A (HEMA) [MIM:306700] 218 349 Cu-oxidase
P00451 M339T Hemophilia A (HEMA) [MIM:306700] 218 349 Cu-oxidase
P00451 V345A Hemophilia A (HEMA) [MIM:306700] 218 349 Cu-oxidase
P00480 L244Q Ornithine carbamoyltransferase deficiency (OTCD) [MIM:311250] 187 341 OTCace Purine nucleoside phosphorylase deficiency (PNPD) P00491 A174P [MIM:613179] 26 280 PNP_UDP_1
P00740 C108S Hemophilia B (HEMB) [MIM:306900] 97 127 EGF
P00740 V419E Hemophilia B (HEMB) [MIM:306900] 227 454 Trypsin
P00740 L52S Hemophilia B (HEMB) [MIM:306900] 52 92 Gla
P00746 V213G Complement factor D deficiency (CFDD) [MIM:613912] 26 248 Trypsin
P00748 C590S Factor XII deficiency (FA12D) [MIM:234000] 373 609 Trypsin
P00966 W179R Citrullinemia 1 (CTLN1) [MIM:215700] 8 403 Arginosuc_synth
P00966 Y190D Citrullinemia 1 (CTLN1) [MIM:215700] 8 403 Arginosuc_synth
P01008 I218N Antithrombin III deficiency (AT3D) [MIM:613118] 85 461 Serpin
P01130 C95G Familial hypercholesterolemia (FH) [MIM:143890] 66 104 Ldl_recept_a
P01130 D221G Familial hypercholesterolemia (FH) [MIM:143890] 195 231 Ldl_recept_a
P01130 C231G Familial hypercholesterolemia (FH) [MIM:143890] 195 231 Ldl_recept_a
P01130 D221N Familial hypercholesterolemia (FH) [MIM:143890] 195 231 Ldl_recept_a
P01137 Y81H Camurati-Engelmann disease (CAEND) [MIM:131300] 29 261 TGFb_propeptide
41 UniProt Mutation Disease Start End Domain
P01185 C92S Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 C92Y Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 R97P Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 C98G Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5
P01185 C98S Diabetes insipidus; neurohypophyseal (NDI) [MIM:125700] 39 116 Hormone_5 Immunoglobulin kappa light chain deficiency (IGKCD) P01834 W41R [MIM:614102] 7 93 C1-set Epidermolysis bullosa simplex; Koebner type (K-EBS) P02533 M272R [MIM:131900] 114 425 Filament Epidermolysis bullosa simplex; Koebner type (K-EBS) P02533 Y415H [MIM:131900] 114 425 Filament Muscular dystrophy congenital LMNA-related (MDCL) P02545 L302P [MIM:613205] 30 386 Filament
P02545 Y481H Limb-girdle muscular dystrophy 1B (LGMD1B) [MIM:159001] 433 544 LTD Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 I63S (EDMD2) [MIM:181350] 30 386 Filament Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 I63N (EDMD2) [MIM:181350] 30 386 Filament Emery-Dreifuss muscular dystrophy 2; autosomal dominant P02545 G449D (EDMD2) [MIM:181350] 433 544 LTD
P02545 I210S Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament
P02545 A318T Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 30 386 Filament
P02549 L260P Elliptocytosis 2 (EL2) [MIM:130600] 158 262 Spectrin
P02671 R129P Congenital afibrinogenemia (CAFBN) [MIM:202400] 49 191 Fib_alpha
P02748 C119G Complement component 9 deficiency (C9D) [MIM:613825] 99 134 Ldl_recept_a Glomerulopathy with fibronectin deposits 2 (GFND2) P02751 W1834R [MIM:601894] 1815 1894 fn3
P02766 Y136S Amyloidosis; transthyretin-related (AMYL-TTR) [MIM:105210] 32 139 Transthyretin Mitochondrial complex V deficiency; mitochondrial 2 (MC5DM2) P03928 W55R [MIM:516070] 1 55 ATP-synt_8
P03928 W55R Cardiomyopathy; infantile hypertrophic (CMHI) [MIM:500006] 1 55 ATP-synt_8
P03950 Y38H Amyotrophic lateral sclerosis 9 (ALS9) [MIM:611895] 28 140 RnaseA
P03951 L360P Factor XI deficiency (FA11D) [MIM:612416] 291 374 PAN_1
P03951 W401R Factor XI deficiency (FA11D) [MIM:612416] 388 618 Trypsin
P04062 A229E Gaucher disease (GD) [MIM:230800] 117 466 Glyco_hydro_30
P04062 A229T Gaucher disease (GD) [MIM:230800] 117 466 Glyco_hydro_30 Thrombophilia due to protein C deficiency; autosomal dominant P04070 R220Q (THPH3) [MIM:176860] 212 445 Trypsin Thrombophilia due to protein C deficiency; autosomal dominant P04070 D401N (THPH3) [MIM:176860] 212 445 Trypsin
P04156 F198S Gerstmann-Straussler disease (GSD) [MIM:137440] 134 252 Prion Hyperornithinemia with gyrate atrophy of choroid and retina P04181 I436N (HOGA) [MIM:258870] 50 436 Aminotran_3
P04264 V155G Epidermolytic hyperkeratosis (EHK) [MIM:113800] 16 176 Keratin_2_head
P04264 L161P Epidermolytic hyperkeratosis (EHK) [MIM:113800] 16 176 Keratin_2_head
P04264 V155D Epidermolytic hyperkeratosis (EHK) [MIM:113800] 16 176 Keratin_2_head
P04264 L486P Epidermolytic hyperkeratosis (EHK) [MIM:113800] 179 492 Filament
P04264 L485P Epidermolytic hyperkeratosis (EHK) [MIM:113800] 179 492 Filament
P04275 R1597G Von Willebrand disease 2 (VWD2) [MIM:613554] 1498 1660 VWA
P04275 V1607D Von Willebrand disease 2 (VWD2) [MIM:613554] 1498 1660 VWA
P04424 L295P Argininosuccinic aciduria (ARGINSA) [MIM:207900] 11 305 Lyase_1
42 UniProt Mutation Disease Start End Domain
P04637 L257Q Li-Fraumeni syndrome (LFS) [MIM:151623] 95 289 P53
P04637 L265P Li-Fraumeni syndrome (LFS) [MIM:151623] 95 289 P53
P04839 L546P Granulomatous disease; chronic; X-linked (CGD) [MIM:306400] 401 551 NAD_binding_6
P05186 Y436H Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05186 S445P Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05186 Y297D Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05186 L299P Hypophosphatasia (HOPS) [MIM:146300] 51 490 Alk_phosphatase
P05549 L249P Branchiooculofacial syndrome (BOFS) [MIM:113620] 211 405 TF_AP-2
P06280 F113S Fabry disease (FD) [MIM:301500] 39 322 Melibiase_2
P06280 R112S Fabry disease (FD) [MIM:301500] 39 322 Melibiase_2
P06280 W262R Fabry disease (FD) [MIM:301500] 39 322 Melibiase_2 Myopathy; congenital; with fiber-type disproportion (CFTD) P06753 L100M [MIM:255310] 49 285 Tropomyosin Myopathy; congenital; with fiber-type disproportion (CFTD) P06753 R91P [MIM:255310] 49 285 Tropomyosin
P06858 I221T Lipoprotein lipase deficiency (LPL deficiency) [MIM:238600] 17 338 Lipase
P06858 S286G Lipoprotein lipase deficiency (LPL deficiency) [MIM:238600] 17 338 Lipase
P06858 L330P Lipoprotein lipase deficiency (LPL deficiency) [MIM:238600] 17 338 Lipase
P07101 L510Q Segawa syndrome autosomal recessive (ARSEGS) [MIM:605407] 195 525 Biopterin_H
P07196 L336P Charcot-Marie-Tooth disease 2E (CMT2E) [MIM:607684] 89 399 Filament
P07202 C808R Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500] 796 838 EGF_CA
P07315 T5P Cataract 2; multiple types (CTRCT2) [MIM:604307] 3 82 Crystall Leukoencephalopathy; diffuse hereditary; with spheroids (HDLS) P07333 I906T [MIM:221820] 582 910 Pkinase_Tyr
P07902 I32N Galactosemia (GALCT) [MIM:230400] 22 196 GalP_UDP_transf
P07902 L74P Galactosemia (GALCT) [MIM:230400] 22 196 GalP_UDP_transf
P07902 A81T Galactosemia (GALCT) [MIM:230400] 22 196 GalP_UDP_transf
P07902 L217P Galactosemia (GALCT) [MIM:230400] 202 370 GalP_UDP_tr_C
P07902 Y34N Galactosemia (GALCT) [MIM:230400] 22 196 GalP_UDP_transf
P07902 Y89H Galactosemia (GALCT) [MIM:230400] 22 196 GalP_UDP_transf
P07902 L267R Galactosemia (GALCT) [MIM:230400] 202 370 GalP_UDP_tr_C
P07949 R972G Hirschsprung disease 1 (HSCR1) [MIM:142623] 724 1005 Pkinase_Tyr
P07949 F174S Hirschsprung disease 1 (HSCR1) [MIM:142623] 172 262 Cadherin Charcot-Marie-Tooth disease; X-linked dominant; 1 (CMTX1) P08034 L108P [MIM:302800] 2 214 Connexin
P08236 C38G Mucopolysaccharidosis 7 (MPS7) [MIM:253220] 38 224 Glyco_hydro_2_N
P08514 F320S Glanzmann thrombasthenia (GT) [MIM:273800] 320 362 FG-GAP
P08514 R755P Glanzmann thrombasthenia (GT) [MIM:273800] 481 921 Integrin_alpha2
P08514 L847P Glanzmann thrombasthenia (GT) [MIM:273800] 481 921 Integrin_alpha2
P08603 C1043R Hemolytic uremic syndrome atypical 1 (AHUS1) [MIM:235400] 989 1043 Sushi
P08603 W1157R Hemolytic uremic syndrome atypical 1 (AHUS1) [MIM:235400] 1109 1163 Sushi
P08603 C915S Hemolytic uremic syndrome atypical 1 (AHUS1) [MIM:235400] 870 926 Sushi
P08603 D1119G Complement factor H deficiency (CFHD) [MIM:609814] 1109 1163 Sushi
P08709 D277N Factor VII deficiency (FA7D) [MIM:227500] 213 447 Trypsin
43 UniProt Mutation Disease Start End Domain
P08779 K354N Pachyonychia congenita 1 (PC1) [MIM:167200] 116 427 Filament
P08779 L421P Pachyonychia congenita 1 (PC1) [MIM:167200] 116 427 Filament
P08842 W372R Ichthyosis; X-linked (IXL) [MIM:308100] 27 413 Sulfatase
P08842 W372S Ichthyosis; X-linked (IXL) [MIM:308100] 27 413 Sulfatase
P0CW18 R176G Microphthalmia; isolated; 6 (MCOP6) [MIM:613517] 105 332 Trypsin
P0CW18 W309S Microphthalmia; isolated; 6 (MCOP6) [MIM:613517] 105 332 Trypsin
P10253 L291P Glycogen storage disease 2 (GSD2) [MIM:232300] 254 320 Gal_mutarotas_2
P10275 L257P Androgen insensitivity syndrome (AIS) [MIM:300068] 6 449 Androgen_recep
P10746 L237P Congenital erythropoietic porphyria (CEP) [MIM:263700] 17 253 HEM4
P10828 L341P Generalized thyroid hormone resistance (GTHR) [MIM:188570] 265 445 Hormone_recep
P10912 W68R Laron syndrome (LARS) [MIM:262500] 43 144 EpoR_lig-bind
P11172 V109G Orotic aciduria 1 (ORAC1) [MIM:258900] 40 168 Pribosyltran
P11362 I300T Trigonocephaly 1 (TRIGNO1) [MIM:190440] 259 358 I-set Hypogonadotropic hypogonadism 2 with or without anosmia (HH2) P11362 V174A [MIM:147950] 160 247 I-set
P11362 L165S Hartsfield syndrome (HRTFDS) [MIM:615465] 160 247 I-set
P11362 L191S Hartsfield syndrome (HRTFDS) [MIM:615465] 160 247 I-set Deafness with labyrinthine aplasia; microtia and microdontia P11487 S156P (LAMM) [MIM:610706] 44 179 FGF
P12034 Y174H Trichomegaly (TCMGLY) [MIM:190330] 87 216 FGF
P12883 L1706P Myopathy; distal; 1 (MPD1) [MIM:160500] 843 1924 Myosin_tail_1
P12883 R870H Cardiomyopathy; familial hypertrophic 1 (CMH1) [MIM:192600] 843 1924 Myosin_tail_1
P12883 R663S Cardiomyopathy; familial hypertrophic 1 (CMH1) [MIM:192600] 87 766 Myosin_head
P12883 R869G Cardiomyopathy; familial hypertrophic 1 (CMH1) [MIM:192600] 843 1924 Myosin_tail_1
P12883 L1135R Cardiomyopathy; familial hypertrophic 1 (CMH1) [MIM:192600] 843 1924 Myosin_tail_1
P12883 A1379T Cardiomyopathy; familial hypertrophic 1 (CMH1) [MIM:192600] 843 1924 Myosin_tail_1
P13569 V754M Cystic fibrosis (CF) [MIM:219700] 639 849 CFTR_R Congenital bilateral absence of the vas deferens (CBAVD) P13569 A800G [MIM:277180] 639 849 CFTR_R
P13645 I446T Ichthyosis annular epidermolytic (AEI) [MIM:607602] 145 459 Filament Epidermolysis bullosa simplex; Weber-Cockayne type (WC-EBS) P13647 I161S [MIM:131800] 16 164 Keratin_2_head Epidermolysis bullosa simplex; Weber-Cockayne type (WC-EBS) P13647 V324D [MIM:131800] 167 480 Filament Epidermolysis bullosa simplex; Koebner type (K-EBS) P13647 V323A [MIM:131900] 167 480 Filament Epidermolysis bullosa simplex; Koebner type (K-EBS) P13647 L325P [MIM:131900] 167 480 Filament Epidermolysis bullosa simplex; Koebner type (K-EBS) P13647 V143D [MIM:131900] 16 164 Keratin_2_head
P14136 R258P Alexander disease (ALXDRD) [MIM:203450] 68 376 Filament
P14136 L235P Alexander disease (ALXDRD) [MIM:203450] 68 376 Filament
P14136 Y242D Alexander disease (ALXDRD) [MIM:203450] 68 376 Filament
P14770 N61S Bernard-Soulier syndrome (BSS) [MIM:231200] 50 86 LRR_8
P14770 F71S Bernard-Soulier syndrome (BSS) [MIM:231200] 50 86 LRR_8
P15056 I463S Colorectal cancer (CRC) [MIM:114500] 457 714 Pkinase_Tyr
P15056 F468S Cardiofaciocutaneous syndrome 1 (CFC1) [MIM:115150] 457 714 Pkinase_Tyr
P15289 L135P Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
44 UniProt Mutation Disease Start End Domain
P15289 C156R Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
P15289 Y306H Leukodystrophy metachromatic (MLD) [MIM:250100] 21 346 Sulfatase
P15289 C489G Leukodystrophy metachromatic (MLD) [MIM:250100] 368 502 Sulfatase_C Renal tubular acidosis; distal; with progressive nerve deafness P15313 L81P (dRTA-D) [MIM:267300] 44 110 ATP-synt_ab_N
P15538 W116G Adrenal hyperplasia 4 (AH4) [MIM:202010] 42 498 p450
P16157 L276R Spherocytosis 1 (SPH1) [MIM:182900] 271 303 Ank
P16278 L264S GM1-gangliosidosis 2 (GM1G2) [MIM:230600] 40 357 Glyco_hydro_35
P16278 L337P GM1-gangliosidosis 2 (GM1G2) [MIM:230600] 40 357 Glyco_hydro_35
P16278 L337P GM1-gangliosidosis 1 (GM1G1) [MIM:230500] 40 357 Glyco_hydro_35
P16930 V166G Tyrosinemia 1 (TYRSN1) [MIM:276700] 123 413 FAA_hydrolase
P17302 L113P Oculodentodigital dysplasia (ODDD) [MIM:164200] 3 233 Connexin
P17405 L225P Niemann-Pick disease B (NPDB) [MIM:607616] 199 461 Metallophos
P17405 C226R Niemann-Pick disease A (NPDA) [MIM:257200] 199 461 Metallophos
P17661 L345P Myopathy; myofibrillar; 1 (MFM1) [MIM:601419] 107 415 Filament
P17661 L385P Myopathy; myofibrillar; 1 (MFM1) [MIM:601419] 107 415 Filament
P17661 R355P Myopathy; myofibrillar; 1 (MFM1) [MIM:601419] 107 415 Filament
P17661 L370P Myopathy; myofibrillar; 1 (MFM1) [MIM:601419] 107 415 Filament
P17813 C412S Telangiectasia; hereditary hemorrhagic; 1 (HHT1) [MIM:187300] 363 564 Zona_pellucida
P19429 A171T Cardiomyopathy; familial restrictive 1 (RCM1) [MIM:115210] 46 177 Troponin
P19544 C355G Wilms tumor 1 (WT1) [MIM:194070] 353 377 zf-C2H2
P19544 C388R Nephrotic syndrome 4 (NPHS4) [MIM:256370] 383 405 zf-C2H2
P19544 C360G Denys-Drash syndrome (DDS) [MIM:194080] 353 377 zf-C2H2
P19544 C385R Denys-Drash syndrome (DDS) [MIM:194080] 383 405 zf-C2H2
P19544 C388F Denys-Drash syndrome (DDS) [MIM:194080] 383 405 zf-C2H2
P19544 C388Y Denys-Drash syndrome (DDS) [MIM:194080] 383 405 zf-C2H2
P20823 I128N Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496] 8 168 HNF-1_N
P20823 V133M Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496] 8 168 HNF-1_N
P20823 C241G Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496] 200 275 Homeobox
P20823 I618M Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496] 542 630 HNF-1A_C
P20823 C241G Diabetes mellitus; insulin-dependent; 20 (IDDM20) [MIM:612520] 200 275 Homeobox
P20908 C1639S Ehlers-Danlos syndrome; classic type (EDS) [MIM:130000] 1607 1836 COLFI
P21333 V711D Cardiac valvular dysplasia X-linked (CVDX) [MIM:314400] 669 760 Filamin
P21817 E160G Central core disease of muscle (CCD) [MIM:117000] 8 210 Ins145_P3_rec
P21817 I4898T Central core disease of muscle (CCD) [MIM:117000] 4773 4949 Ion_trans
P22033 L617R Methylmalonic aciduria type mut (MMAM) [MIM:251000] 615 733 B12-binding
P22033 L518P Methylmalonic aciduria type mut (MMAM) [MIM:251000] 62 574 MM_CoA_mutase
P22033 L140P Methylmalonic aciduria type mut (MMAM) [MIM:251000] 62 574 MM_CoA_mutase
P22304 D148H Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
P22304 L182P Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
P22304 A205P Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
P22304 L259P Mucopolysaccharidosis 2 (MPS2) [MIM:309900] 37 416 Sulfatase
45 UniProt Mutation Disease Start End Domain
P22309 L443P Crigler-Najjar syndrome 2 (CN2) [MIM:606785] 28 524 UDPGT
P22557 R452G Anemia; sideroblastic; 1 (SIDBA1) [MIM:300751] 189 536 Aminotran_1_2 Ichthyosis; congenital; autosomal recessive 1 (ARCI1) P22735 L205Q [MIM:242300] 109 227 Transglut_N Cortical dysplasia; complex; with other brain malformations 4 P23258 L387P (CDCBM4) [MIM:615412] 264 392 Tubulin_C
P23760 I59N Waardenburg syndrome 1 (WS1) [MIM:193500] 34 159 PAX
P23942 C214S Retinitis pigmentosa 7 (RP7) [MIM:608133] 16 287 Tetraspannin Merosin-deficient congenital muscular dystrophy 1A (MDC1A) P24043 C862R [MIM:607855] 807 862 Laminin_EGF Merosin-deficient congenital muscular dystrophy 1A (MDC1A) P24043 L2564P [MIM:607855] 2554 2695 Laminin_G_1 Autoimmune lymphoproliferative syndrome 1A (ALPS1A) P25445 I259R [MIM:601859] 230 314 Death
P26367 F258S Coloboma; ocular; autosomal dominant (COAD) [MIM:120200] 211 267 Homeobox
P26367 F258S Coloboma of optic nerve (COLON) [MIM:120430] 211 267 Homeobox
P26367 I29S Aniridia 1 (AN1) [MIM:106210] 4 128 PAX
P26367 V126D Aniridia 1 (AN1) [MIM:106210] 4 128 PAX
P26440 R50P Isovaleric acidemia (IVA) [MIM:243500] 43 157 Acyl-CoA_dh_N X-linked immunodeficiency with hyper-IgM 1 (HIGM1) P29965 T211N [MIM:308230] 138 261 TNF
P30566 S447P Adenylosuccinase deficiency (ADSLD) [MIM:103050] 378 460 ADSL_C
P30566 R452P Adenylosuccinase deficiency (ADSLD) [MIM:103050] 378 460 ADSL_C
P30613 E387G Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200] 85 438 PK
P30793 R88P Dystonia; dopa-responsive (DRD) [MIM:128230] 71 249 GTP_cyclohydroI
P30793 F234S Dystonia; dopa-responsive (DRD) [MIM:128230] 71 249 GTP_cyclohydroI
P30793 L71Q Dystonia; dopa-responsive (DRD) [MIM:128230] 71 249 GTP_cyclohydroI Carbamoyl phosphate synthetase 1 deficiency (CPS1D) P31327 L843S [MIM:237300] 841 962 CPSase_L_D3 Carbamoyl phosphate synthetase 1 deficiency (CPS1D) P31327 S1203P [MIM:237300] 1088 1291 CPSase_L_D2 Myopathy; vacuolar; with CASQ1 aggregates (VMCQA) P31415 D244G [MIM:616231] 11 396 Calsequestrin Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS) P32004 L935P [MIM:307000] 919 1004 fn3 Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS) P32004 S542P [MIM:307000] 519 595 Ig_3
P33897 M566K Adrenoleukodystrophy (ALD) [MIM:300100] 490 633 ABC_tran
P33897 L190P Adrenoleukodystrophy (ALD) [MIM:300100] 65 352 ABC_membrane_2
P34059 F156S Mucopolysaccharidosis 4A (MPS4A) [MIM:253000] 31 355 Sulfatase
P34059 V48G Mucopolysaccharidosis 4A (MPS4A) [MIM:253000] 31 355 Sulfatase
P35221 L318S Macular dystrophy; patterned; 2 (MDPT2) [MIM:608970] 19 339 Vinculin
P35240 L535P Neurofibromatosis 2 (NF2) [MIM:101000] 347 595 ERM
P35475 R492P Mucopolysaccharidosis 1S (MPS1S) [MIM:607016] 23 543 Glyco_hydro_39
P35475 T103P Mucopolysaccharidosis 1H (MPS1H) [MIM:607014] 23 543 Glyco_hydro_39
P35498 C1756G Epileptic encephalopathy; early infantile; 6 (EIEE6) [MIM:607208] 1540 1797 Ion_trans
P35520 A231P Cystathionine beta-synthase deficiency (CBSD) [MIM:236200] 80 376 PALP
P35527 C406R Keratoderma; palmoplantar; epidermolytic (EPPK) [MIM:144200] 152 464 Filament
P35555 C2652G Marfan syndrome (MFS) [MIM:154700] 2648 2686 EGF_CA
P35555 C2663S Marfan syndrome (MFS) [MIM:154700] 2648 2686 EGF_CA
46 UniProt Mutation Disease Start End Domain
P35555 C699S Marfan syndrome (MFS) [MIM:154700] 669 714 TB
P35555 T2561P Marfan syndrome (MFS) [MIM:154700] 2547 2570 cEGF
P35557 Y108H Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851] 15 215 Hexokinase_1
P35557 I110T Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851] 15 215 Hexokinase_1
P35670 I857T Wilson disease (WD) [MIM:277900] 797 1005 E1-E2_ATPase
P35670 E1068G Wilson disease (WD) [MIM:277900] 1021 1279 Hydrolase
P35670 A861T Wilson disease (WD) [MIM:277900] 797 1005 E1-E2_ATPase
P35670 A1065P Wilson disease (WD) [MIM:277900] 1021 1279 Hydrolase Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) P35713 W95R [MIM:607823] 85 153 HMG_box
P35908 I182N Ichthyosis bullosa of Siemens (IBS) [MIM:146800] 177 490 Filament
P36551 L214R Hereditary coproporphyria (HCP) [MIM:121300] 151 453 Coprogen_oxidas
P36871 T19A Congenital disorder of glycosylation 1T (CDG1T) [MIM:614921] 14 158 PGM_PMM_I
P37173 A355P Loeys-Dietz syndrome 2 (LDS2) [MIM:610168] 244 538 Pkinase_Tyr
P37840 A30P Parkinson disease 1; autosomal dominant (PARK1) [MIM:168601] 1 131 Synuclein
P38398 C61G Ovarian cancer (OC) [MIM:167000] 24 64 zf-C3HC4
P38398 C61G Breast cancer (BC) [MIM:114480] 24 64 zf-C3HC4
P38398 Y465D Breast cancer (BC) [MIM:114480] 345 508 BRCT_assoc
P40337 V74G Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 W88R Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 W88S Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 Q96P Von Hippel-Lindau disease (VHLD) [MIM:193300] 63 144 VHL
P40337 L188P Von Hippel-Lindau disease (VHLD) [MIM:193300] 149 204 VHL_C
P42224 C174R Immunodeficiency 31C (IMD31C) [MIM:614162] 139 315 STAT_alpha
P42768 L270P Neutropenia; severe congenital; X-linked (XLN) [MIM:300299] 237 296 PBD
P43026 L441P Multiple synostoses syndrome 2 (SYNS2) [MIM:610017] 398 500 TGF_beta
P43026 L441P Du Pan syndrome (DPS) [MIM:228900] 398 500 TGF_beta
P43026 L441P Brachydactyly A2 (BDA2) [MIM:112600] 398 500 TGF_beta Hereditary non-polyposis colorectal cancer 1 (HNPCC1) P43246 V470E [MIM:120435] 305 609 MutS_III
P43699 R213S Chorea; hereditary benign (BHC) [MIM:118700] 162 218 Homeobox
P43699 W208S Chorea; hereditary benign (BHC) [MIM:118700] 162 218 Homeobox
P45452 W207G Metaphyseal dysplasia; Spahr type (MDST) [MIM:250400] 112 267 Peptidase_M10
P48436 W143R Campomelic dysplasia (CMD1) [MIM:114290] 105 173 HMG_box
P48637 L301P Glutathione synthetase deficiency (GSS deficiency) [MIM:266130] 204 302 GSH_synthase
P49419 V395G Pyridoxine-dependent epilepsy (PDE) [MIM:266100] 59 522 Aldedh
P49918 L53P Beckwith-Wiedemann syndrome (BWS) [MIM:130650] 32 82 CDI
P50219 R245G Currarino syndrome (CURRAS) [MIM:176450] 242 298 Homeobox
P50336 L85P Variegate porphyria (VP) [MIM:176200] 12 471 Amino_oxidase
P50336 L154P Variegate porphyria (VP) [MIM:176200] 12 471 Amino_oxidase
P50336 V335G Variegate porphyria (VP) [MIM:176200] 12 471 Amino_oxidase
P50570 L621P Myopathy; centronuclear; 1 (CNM1) [MIM:160150] 520 624 PH
47 UniProt Mutation Disease Start End Domain
P50897 L305P Ceroid lipofuscinosis; neuronal; 1 (CLN1) [MIM:256730] 28 306 Palm_thioest
P51531 R855G Nicolaides-Baraitser syndrome (NCBRS) [MIM:601358] 710 1022 SNF2_N Fanconi anemia complementation group D1 (FANCD1) P51587 L2510P [MIM:605724] 2481 2667 BRCA-2_helical
P51608 Y120D Rett syndrome (RTT) [MIM:312750] 91 162 MBD
P51648 F419S Sjoegren-Larsson syndrome (SLS) [MIM:270200] 2 424 Aldedh
P51688 Y40N Mucopolysaccharidosis 3A (MPS3A) [MIM:252900] 23 328 Sulfatase
P51688 T79P Mucopolysaccharidosis 3A (MPS3A) [MIM:252900] 23 328 Sulfatase
P51688 R206P Mucopolysaccharidosis 3A (MPS3A) [MIM:252900] 23 328 Sulfatase
P51787 I567S Long QT syndrome 1 (LQT1) [MIM:192500] 481 620 KCNQ_channel
P51787 A590T Long QT syndrome 1 (LQT1) [MIM:192500] 481 620 KCNQ_channel
P51787 I567T Long QT syndrome 1 (LQT1) [MIM:192500] 481 620 KCNQ_channel Atrial septal defect 7; with or without atrioventricular conduction P52952 L144P defects (ASD7) [MIM:108900] 139 195 Homeobox Mitochondrial DNA depletion syndrome 4A (MTDPS4A) P54098 A767D [MIM:203700] 754 1185 DNA_pol_A
P54802 G69S Mucopolysaccharidosis 3B (MPS3B) [MIM:252920] 30 116 NAGLU_N
P54821 F113S Agnathia-otocephaly complex (AGOTC) [MIM:202650] 95 151 Homeobox
P54845 R170S Retinitis pigmentosa 27 (RP27) [MIM:613750] 132 223 bZIP_Maf
P55017 L215P Gitelman syndrome (GTLMNS) [MIM:263800] 141 647 AA_permease Inclusion body myopathy with early-onset Paget disease with or P55072 R191Q without frontotemporal dementia 1 (IBMPFD1) [MIM:167320] 125 191 CDC48_2 Amyotrophic lateral sclerosis 14; with or without frontotemporal P55072 R191Q dementia (ALS14) [MIM:613954] 125 191 CDC48_2 Mitochondrial trifunctional protein deficiency (MTPD) P55084 L121P [MIM:609015] 54 324 Thiolase_N Succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOTD) P55809 V133E [MIM:245050] 43 272 CoA_trans
P56693 L145P Waardenburg syndrome 4C (WS4C) [MIM:613266] 104 172 HMG_box Peripheral demyelinating neuropathy; central dysmyelinating leukodystrophy; Waardenburg syndrome and Hirschsprung disease P56693 K150N (PCWH) [MIM:609136] 104 172 HMG_box
P56715 L172R Retinitis pigmentosa 1 (RP1) [MIM:180100] 171 227 DCX Blepharophimosis; ptosis; and epicanthus inversus syndrome P58012 W98G (BPES) [MIM:110100] 54 139 Forkhead
P60484 K289E Cowden syndrome 1 (CWS1) [MIM:158350] 188 349 PTEN_C2
P61916 C99R Niemann-Pick disease C2 (NPC2) [MIM:607625] 21 147 E1_DerP2_DerF2
P78363 I824T Stargardt disease 1 (STGD1) [MIM:248200] 607 856 ABC2_membrane_3
P78504 C753R Alagille syndrome 1 (ALGS1) [MIM:118450] 748 777 EGF
P78504 C92R Alagille syndrome 1 (ALGS1) [MIM:118450] 32 107 MNNL
P78504 C92Y Alagille syndrome 1 (ALGS1) [MIM:118450] 32 107 MNNL Hypophosphatemic rickets; X-linked dominant (XLHR) P78562 C733S [MIM:307800] 538 748 Peptidase_M13
P82279 C891G Retinitis pigmentosa 12 (RP12) [MIM:600105] 891 920 EGF
P82279 C157S Retinitis pigmentosa 12 (RP12) [MIM:600105] 152 182 EGF
P98161 C508R Polycystic kidney disease 1 (PKD1) [MIM:173900] 425 532 Lectin_C
P98161 L3154P Polycystic kidney disease 1 (PKD1) [MIM:173900] 3120 3231 PLAT
P98161 R3750Q Polycystic kidney disease 1 (PKD1) [MIM:173900] 3711 4113 PKD_channel
P98172 C153S Craniofrontonasal syndrome (CFNS) [MIM:304110] 30 164 Ephrin Mental retardation; autosomal dominant 31 (MRD31) Q00577 L100P [MIM:616158] 58 278 PurA
48 UniProt Mutation Disease Start End Domain
Q00604 C39R Norrie disease (ND) [MIM:310600] 37 133 Cys_knot
Q00604 C69S Norrie disease (ND) [MIM:310600] 37 133 Cys_knot
Q03252 Y252H Partial acquired lipodystrophy (APLD) [MIM:608709] 45 401 Filament
Q04695 L388P Pachyonychia congenita 2 (PC2) [MIM:167210] 83 394 Filament
Q04771 R375P Fibrodysplasia ossificans progressiva (FOP) [MIM:135100] 208 495 Pkinase
Q05066 V60A 46;XY sex reversal 1 (SRXY1) [MIM:400044] 60 128 HMG_box
Q05066 I68T 46;XY sex reversal 1 (SRXY1) [MIM:400044] 60 128 HMG_box
Q05066 F67V 46;XY sex reversal 1 (SRXY1) [MIM:400044] 60 128 HMG_box
Q06124 F285S Noonan syndrome 1 (NS1) [MIM:163950] 273 524 Y_phosphatase
Q06187 L295P X-linked agammaglobulinemia (XLA) [MIM:300755] 281 362 SH2
Q06187 V64D X-linked agammaglobulinemia (XLA) [MIM:300755] 4 133 PH Myasthenic syndrome; congenital; 3B; fast-channel (CMS3B) Q07001 L42P [MIM:616322] 25 246 Neur_chan_LBD
Q12756 R216P Mental retardation; autosomal dominant 9 (MRD9) [MIM:614255] 11 354 Kinesin
Q12756 L249Q Mental retardation; autosomal dominant 9 (MRD9) [MIM:614255] 11 354 Kinesin
Q12809 I593R Long QT syndrome 2 (LQT2) [MIM:613688] 407 671 Ion_trans
Q12809 I593T Long QT syndrome 2 (LQT2) [MIM:613688] 407 671 Ion_trans
Q12948 I126S Axenfeld-Rieger syndrome 3 (RIEG3) [MIM:602482] 78 163 Forkhead
Q13253 A36P Brachydactyly B2 (BDB2) [MIM:611377] 12 232 Noggin
Q13315 V2424G T-prolymphocytic leukemia 2096 2489 FAT
Q13315 V2424G B-cell chronic lymphocytic leukemia 2096 2489 FAT
Q13315 V2424G Ataxia telangiectasia (AT) [MIM:208900] 2096 2489 FAT Short stature; microcephaly; and endocrine dysfunction (SSMED) Q13426 W43R [MIM:616541] 1 334 XRCC4
Q13496 V364G Myopathy; centronuclear; X-linked (CNMX) [MIM:310400] 149 487 Myotub-related
Q13563 A356P Polycystic kidney disease 2 (PKD2) [MIM:613095] 267 687 PKD_channel Myasthenic syndrome; congenital; 11; associated with Q13702 L14P acetylcholine receptor deficiency (CMS11) [MIM:616326] 1 80 Rapsyn_N
Q13950 F197S Cleidocranial dysplasia (CLCD) [MIM:119600] 102 231 Runt
Q13950 F187S Cleidocranial dysplasia (CLCD) [MIM:119600] 102 231 Runt
Q14117 W360R Dihydropyrimidinase deficiency (DPYSD) [MIM:222748] 58 447 Amidohydro_1
Q14203 M571T Amyotrophic lateral sclerosis (ALS) [MIM:105400] 527 805 Dynactin Anhidrosis; isolated; with normal sweat glands (ANHD) Q14571 G2498S [MIM:106190] 2260 2552 Ion_trans
Q14654 C42R Transient neonatal diabetes mellitus 3 (TNDM3) [MIM:610582] 36 360 IRK
Q14683 R711Q Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590] 3 1211 SMC_N
Q14896 W792R Cardiomyopathy; familial hypertrophic 4 (CMH4) [MIM:115197] 773 858 fn3
Q14999 L1014R 3M syndrome 1 (3M1) [MIM:273750] 946 1524 Cullin
Q15319 L223P Deafness; autosomal dominant; 15 (DFNA15) [MIM:602459] 182 256 Pou
Q15437 V594G Cowden syndrome 7 (CWS7) [MIM:616858] 520 619 Sec23_helical
Q15465 G143D Holoprosencephaly 3 (HPE3) [MIM:142945] 24 184 HH_signal
Q15465 R144P Holoprosencephaly 3 (HPE3) [MIM:142945] 24 184 HH_signal
Q15465 C198S Holoprosencephaly 3 (HPE3) [MIM:142945] 187 448 Hint
Q15831 W308C Peutz-Jeghers syndrome (PJS) [MIM:175200] 49 309 Pkinase
49 UniProt Mutation Disease Start End Domain
Q16586 I103T Limb-girdle muscular dystrophy 2D (LGMD2D) [MIM:608099] 7 382 Sarcoglycan_2
Q16586 I124T Limb-girdle muscular dystrophy 2D (LGMD2D) [MIM:608099] 7 382 Sarcoglycan_2
Q16595 W155R Friedreich ataxia (FRDA) [MIM:229300] 90 198 Frataxin_Cyay
Q16644 L173P Macular dystrophy; patterned; 3 (MDPT3) [MIM:617111] 44 304 Pkinase
Q16678 M132R Glaucoma 3; primary congenital; A (GLC3A) [MIM:231300] 51 520 p450
Q16678 E499G Glaucoma 3; primary congenital; A (GLC3A) [MIM:231300] 51 520 p450
Q16740 Y229D Perrault syndrome 3 (PRLTS3) [MIM:614129] 67 248 CLP_protease Cerebroretinal microangiopathy with calcifications and cysts 1 Q2NKJ3 V871M (CRMCC1) [MIM:612199] 61 1201 CTC1 Mucolipidosis type III complementation group A (MLIIIA) Q3T906 C468S [MIM:252600] 435 469 Notch
Q4KMG0 V780E Holoprosencephaly 11 (HPE11) [MIM:614226] 722 807 fn3
Q5HYA8 R820S COACH syndrome (COACHS) [MIM:216360] 167 995 Meckelin Combined oxidative phosphorylation deficiency 20 (COXPD20) Q5ST30 A349T [MIM:615917] 112 735 tRNA-synt_1
Q5TBB1 V185G Aicardi-Goutieres syndrome 2 (AGS2) [MIM:610181] 15 301 RNase_H2-Ydr279
Q6JEL2 Q216P Spermatogenic failure 11 (SPGF11) [MIM:615081] 141 244 BACK Hennekam lymphangiectasia-lymphedema syndrome 1 (HKLLS1) Q6UXH8 C174R [MIM:235510] 134 174 EGF_CA
Q6ZUT3 L142R Nystagmus congenital X-linked 1 (NYS1) [MIM:310700] 85 192 FERM_M
Q6ZVN8 F170S Hemochromatosis 2A (HFE2A) [MIM:602390] 37 226 RGM_N
Q6ZVN8 D172E Hemochromatosis 2A (HFE2A) [MIM:602390] 37 226 RGM_N Thrombotic thrombocytopenic purpura congenital (TTP) Q76LX8 C1024G [MIM:274150] 1018 1058 TSP_1 Thrombotic thrombocytopenic purpura congenital (TTP) Q76LX8 L232Q [MIM:274150] 81 286 Reprolysin Mental retardation; X-linked; syndromic; Turner type (MRXST) Q7Z6Z7 R2981H [MIM:300706] 2968 3079 DUF4414
Q8IU80 D521G Iron-refractory iron deficiency anemia (IRIDA) [MIM:206200] 490 525 Ldl_recept_a
Q8IV16 C83R Hyperlipoproteinemia 1D (HLPP1D) [MIM:615947] 65 137 UPAR_LY6
Q8IWV7 I286R Johanson-Blizzard syndrome (JBS) [MIM:243800] 221 301 ClpS
Q8NC56 L13R Cataract 46; juvenile-onset (CTRCT46) [MIM:212500] 1 39 LEM Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) Q8NCM8 W3847G [MIM:613091] 3613 4304 Dynein_heavy Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) Q8NCM8 L4232R [MIM:613091] 3613 4304 Dynein_heavy Factor V and factor VIII combined deficiency 2 (F5F8D2) Q8NI22 Y135N [MIM:613625] 70 146 EF-hand_7
Q8TAB3 V441E Epileptic encephalopathy; early infantile; 9 (EIEE9) [MIM:300088] 354 444 Cadherin
Q8TAB3 L543P Epileptic encephalopathy; early infantile; 9 (EIEE9) [MIM:300088] 458 554 Cadherin
Q8TAB3 V72G Epileptic encephalopathy; early infantile; 9 (EIEE9) [MIM:300088] 24 109 Cadherin_2
Q8TAB3 L433P Epileptic encephalopathy; early infantile; 9 (EIEE9) [MIM:300088] 354 444 Cadherin Spinal muscular atrophy; lower extremity-predominant 2; Q8TD16 R501P autosomal dominant (SMALED2) [MIM:615290] 83 801 BicD Spinal muscular atrophy; lower extremity-predominant 2; Q8TD16 K508T autosomal dominant (SMALED2) [MIM:615290] 83 801 BicD
Q92947 R138G Glutaric aciduria 1 (GA1) [MIM:231670] 61 172 Acyl-CoA_dh_N
Q92947 L179R Glutaric aciduria 1 (GA1) [MIM:231670] 176 269 Acyl-CoA_dh_M
Q93099 W97G Alkaptonuria (AKU) [MIM:203500] 5 434 HgmA
Q93099 W97R Alkaptonuria (AKU) [MIM:203500] 5 434 HgmA
Q969G3 Y73S Coffin-Siris syndrome 5 (CSS5) [MIM:616938] 66 134 HMG_box
50 UniProt Mutation Disease Start End Domain Short-rib thoracic dysplasia 11 with or without polydactyly Q96EX3 G393S (SRTD11) [MIM:615633] 384 421 WD40
Q96P20 V200M Muckle-Wells syndrome (MWS) [MIM:191900] 140 210 FISNA Familial cold autoinflammatory syndrome 1 (FCAS1) Q96P20 V200M [MIM:120100] 140 210 FISNA
Q96PV0 W362R Mental retardation; autosomal dominant 5 (MRD5) [MIM:612621] 262 365 C2
Q96QS3 L343Q Lissencephaly; X-linked 2 (LISX2) [MIM:300215] 329 385 Homeobox Microcephaly; seizures; and developmental delay (MCSZ) Q96T60 R462P [MIM:613402] 367 489 AAA_33
Q99081 L600P Craniosynostosis 3 (CRS3) [MIM:615314] 578 631 HLH
Q99081 Q614E Craniosynostosis 3 (CRS3) [MIM:615314] 578 631 HLH
Q99456 L132P Corneal dystrophy; Meesmann (MECD) [MIM:122100] 124 439 Filament
Q99456 L433R Corneal dystrophy; Meesmann (MECD) [MIM:122100] 124 439 Filament
Q99519 L363P Sialidosis (SIALIDOSIS) [MIM:256550] 88 381 BNR_2
Q99972 I360N Glaucoma 1; open angle; A (GLC1A) [MIM:137750] 248 501 OLF Cardiomyopathy; familial hypertrophic 17 (CMH17) Q9BR39 Y141H [MIM:613873] 129 151 MORN Cortical dysplasia; complex; with other brain malformations 7 Q9BVA1 L117P (CDCBM7) [MIM:610031] 3 212 Tubulin
Q9BXM7 L489P Parkinson disease 6 (PARK6) [MIM:605909] 264 509 Pkinase Neurodegeneration with brain iron accumulation 1 (NBIA1) Q9BZ23 L413P [MIM:234200] 213 565 Fumble Mental retardation; X-linked; syndromic; 14 (MRXS14) Q9BZI7 Y160D [MIM:300676] 48 209 Smg4_UPF3
Q9H270 C846G Leukodystrophy; hypomyelinating; 12 (HLD12) [MIM:616683] 821 860 zf-C3HC4_2 Ectrodactyly; ectodermal dysplasia; and cleft lip/palate syndrome 3 Q9H3D4 R266Q (EEC3) [MIM:604292] 163 359 P53 Ectrodactyly; ectodermal dysplasia; and cleft lip/palate syndrome 3 Q9H3D4 C347S (EEC3) [MIM:604292] 163 359 P53
Q9H4F8 T283N Ophthalmoacromelic syndrome (OAS) [MIM:206920] 227 292 Thyroglobulin_1 Acyl-CoA dehydrogenase family; member 9; deficiency (ACAD9 Q9H845 C271G deficiency) [MIM:611126] 177 278 Acyl-CoA_dh_M
Q9HAN9 V98G Leber congenital amaurosis 9 (LCA9) [MIM:608553] 12 229 CTP_transf_like Auditory neuropathy; autosomal recessive; 1 (AUNB1) Q9HC10 R1939Q [MIM:601071] 1898 1994 Ferlin_C 3-methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D) Q9HCC0 Y520S [MIM:210210] 74 558 Carboxyl_trans
Q9NVV9 Y8C Dystonia 6; torsion (DYT6) [MIM:602629] 5 81 THAP
Q9NVV9 D17G Dystonia 6; torsion (DYT6) [MIM:602629] 5 81 THAP
Q9NVV9 A7D Dystonia 6; torsion (DYT6) [MIM:602629] 5 81 THAP Alopecia; neurologic defects; and endocrinopathy syndrome Q9NW13 L351P (ANES) [MIM:612079] 337 410 RRM_1
Q9NZK5 W264S Polyarteritis nodosa (PAN) [MIM:615688] 174 496 A_deaminase
Q9P2X0 L85S Congenital disorder of glycosylation 1O (CDG1O) [MIM:612937] 1 91 DPM3
Q9UBP0 N386S Spastic paraplegia 4; autosomal dominant (SPG4) [MIM:182601] 378 508 AAA
Q9UBP0 N386K Spastic paraplegia 4; autosomal dominant (SPG4) [MIM:182601] 378 508 AAA
Q9UBP0 L391P Spastic paraplegia 4; autosomal dominant (SPG4) [MIM:182601] 378 508 AAA
Q9UBP0 I580T Spastic paraplegia 4; autosomal dominant (SPG4) [MIM:182601] 563 612 Vps4_C
Q9UDY2 V48A Familial hypercholanemia (FHCA) [MIM:607748] 33 117 PDZ
Q9UKN7 L1806P Deafness; autosomal recessive; 3 (DFNB3) [MIM:600316] 1224 1887 Myosin_head
Q9ULV0 F538S Diarrhea 2; with microvillus atrophy (DIAR2) [MIM:251850] 71 749 Myosin_head Cerebral arteriopathy; autosomal dominant; with subcortical Q9UM47 C212S infarcts and leukoencephalopathy; 1 (CADASIL1) [MIM:125310] 201 232 EGF
51 UniProt Mutation Disease Start End Domain Cerebral arteriopathy; autosomal dominant; with subcortical Q9UM47 C43G infarcts and leukoencephalopathy; 1 (CADASIL1) [MIM:125310] 43 75 EGF Cerebral arteriopathy; autosomal dominant; with subcortical Q9UM47 C174R infarcts and leukoencephalopathy; 1 (CADASIL1) [MIM:125310] 158 201 EGF_CA Cerebral arteriopathy; autosomal dominant; with subcortical Q9UM47 C185G infarcts and leukoencephalopathy; 1 (CADASIL1) [MIM:125310] 158 201 EGF_CA Cerebral arteriopathy; autosomal dominant; with subcortical Q9UM47 C194S infarcts and leukoencephalopathy; 1 (CADASIL1) [MIM:125310] 158 201 EGF_CA Cerebral arteriopathy; autosomal dominant; with subcortical Q9UM47 C775S infarcts and leukoencephalopathy; 1 (CADASIL1) [MIM:125310] 775 806 EGF
Q9Y2S0 L82S Treacher Collins syndrome 2 (TCS2) [MIM:613717] 39 113 RNA_pol_L_2
Q9Y3A0 L52S Coenzyme Q10 deficiency; primary; 7 (COQ10D7) [MIM:616276] 38 258 Coq4 Cleft palate with or without ankyloglossia; X-linked (CPX) Q9Y458 L214P [MIM:303400] 94 283 T-box Methylmalonic aciduria and homocystinuria type cblC Q9Y4U1 L116P (MMAHCC) [MIM:277400] 20 234 MMACHC
Q9Y4W6 Y689H Spinocerebellar ataxia 28 (SCA28) [MIM:610246] 541 744 Peptidase_M41
Q9Y4W6 Y689N Spinocerebellar ataxia 28 (SCA28) [MIM:610246] 541 744 Peptidase_M41
Q9Y6K9 A314P Incontinentia pigmenti (IP) [MIM:308300] 247 344 CC2-LZ
Q9Y6K9 L322P Incontinentia pigmenti (IP) [MIM:308300] 247 344 CC2-LZ Ectodermal dysplasia; anhidrotic; with immunodeficiency X-linked Q9Y6K9 A288G (EDAID) [MIM:300291] 247 344 CC2-LZ
Non-disease mutation
A2VEC9 S1424G - 1414 1452 Ldl_recept_a
A6NGG8 S312N - 1 1264 Retinal
A8MV23 D143N - 29 400 Serpin
O00222 I265T - 74 480 ANF_receptor
O00238 R371Q - 204 491 Pkinase_Tyr
O14633 I51S - 14 110 LCE
O15205 I68T - 10 81 ubiquitin
O15394 L350P - 302 397 I-set
O15492 H137R - 65 180 RGS
O43405 E518G - 367 536 VWA
O43424 F398S - 39 407 ANF_receptor
O43490 A31S - 18 820 Prominin
O43511 L597S - 536 725 STAS
O43511 V609G - 536 725 STAS
O60260 A339S - 313 378 IBR
O60269 V375A - 340 455 GRIN_C
O60294 R141S - 12 207 LCM
O60500 L392P - 344 428 C2-set_2
O75151 T56P - 7 56 PHD
O75351 I58M - 8 74 MIT
O75443 R371G - 322 478 VWD
O75891 L254P - 204 310 Formyl_trans_C
O75891 A436T - 430 898 Aldedh
O75969 I500T - 166 853 AKAP_110
O95163 M182K - 1 954 IKI3
52 UniProt Mutation Disease Start End Domain
O95163 R525Q - 1 954 IKI3
O95278 A46P - 12 117 CBM_20
O95427 H229D - 116 287 Phosphodiest
O95450 V74M - 57 212 Pep_M12B_propep
O95477 I1555T - 1344 1869 ABC2_membrane_3
O95678 R91G - 16 145 Keratin_2_head
O95757 I601T - 571 694 HSP70
O95866 R175G - 18 241 G6B
O95947 P179S - 93 273 T-box
P01130 C109R - 107 143 Ldl_recept_a
P01130 C155G - 146 184 Ldl_recept_a
P01130 D224G - 195 231 Ldl_recept_a
P01241 C79S - 9 215 Hormone_1
P01571 I184R - 26 185 Interferon
P01889 C349S - 337 362 MHC_I_C
P01892 H94Q - 25 203 MHC_I
P01920 Y92N - 45 118 MHC_II_beta
P02042 F86S - 8 112 Globin
P02533 L418Q - 114 425 Filament
P02647 R184P - 69 262 Apolipoprotein
P02649 A117T - 81 292 Apolipoprotein
P02649 V254E - 81 292 Apolipoprotein
P02724 A84P - 34 146 Glycophorin_A
P02749 W335S - 261 345 Sushi_2
P02768 E121G - 30 202 Serum_albumin
P02787 D296G - 25 347 Transferrin
P03989 Y83H - 25 203 MHC_I
P03989 C349S - 337 362 MHC_I_C
P04003 I300T - 299 364 Sushi
P04066 C269S - 24 367 Alpha_L_fucos
P04150 N363S - 26 401 GCR
P04264 I330T - 179 492 Filament
P05106 L59P - 29 76 PSI_integrin
P05154 L115P - 43 406 Serpin
P06731 A340D - 324 397 Ig_3
P07202 A257S - 151 709 An_peroxidase
P07902 L62M - 22 196 GalP_UDP_transf
P07951 Q93H - 48 284 Tropomyosin
P08174 R52P - 36 94 Sushi
P08519 T3907P - 3896 3973 Kringle
P08697 R434K - 84 436 Serpin
53 UniProt Mutation Disease Start End Domain
P09093 H31N - 29 263 Trypsin
P09172 L317P - 214 341 Cu2_monooxygen
P0DJI8 G90D - 22 122 SAA
P10153 H100Q - 33 158 RnaseA
P10321 C350S - 338 365 MHC_I_C
P10635 R343G - 34 494 p450
P10635 V342M - 34 494 p450
P10745 H523Q - 438 617 Peptidase_S41
P10745 V693M - 619 740 Peptidase_S41_N
P11245 V280M - 20 280 Acetyltransf_2
P11464 V134E - 38 144 V-set
P11532 A784G - 721 828 Spectrin
P11532 T409S - 339 447 Spectrin
P11684 R56G - 24 90 Uteroglobin
P11712 L413P - 30 487 p450
P12643 L161S - 35 267 TGFb_propeptide
P12814 T868S - 822 888 EFhand_Ca_insen
P12830 A617T - 598 686 Cadherin
P12882 Q1539H - 847 1928 Myosin_tail_1
P13533 V1101A - 845 1926 Myosin_tail_1
P13535 W1692R - 846 1927 Myosin_tail_1
P13535 I326T - 90 769 Myosin_head
P14678 S79P - 7 82 LSM
P15088 A81S - 27 103 Propep_M14
P16066 V755M - 542 801 Pkinase_Tyr
P17405 V316E - 199 461 Metallophos
P18465 C349S - 337 362 MHC_I_C
P18510 A124T - 60 173 IL1
P19224 R184S - 27 523 UDPGT
P20062 L376S - 352 426 DUF4430
P20309 L431P - 85 544 7tm_1
P20742 T1205P - 1016 1272 A2M_comp
P20815 I488T - 38 492 p450
P21580 A766P - 760 784 zf-A20
P21802 M186T - 162 248 I-set
P21964 A72S - 65 265 Methyltransf_3
P22692 V42G - 27 80 IGFBP
P24557 L512P - 313 530 p450
P24903 R98P - 31 488 p450
P26927 S551G - 484 704 Trypsin
P29320 L590P - 542 618 EphA2_TM
54 UniProt Mutation Disease Start End Domain
P29323 C289G - 261 304 Ephrin_rec_like
P30460 C349S - 337 362 MHC_I_C
P30461 C349S - 337 362 MHC_I_C
P30475 Y123S - 25 203 MHC_I
P30479 C349S - 337 362 MHC_I_C
P30480 C349S - 337 362 MHC_I_C
P30481 C349S - 337 362 MHC_I_C
P30485 C349S - 337 362 MHC_I_C
P30486 C349S - 337 362 MHC_I_C
P30499 W243R - 211 290 C1-set
P30501 K202T - 25 203 MHC_I
P30504 W38R - 25 203 MHC_I
P30504 A97T - 25 203 MHC_I
P30508 A97T - 25 203 MHC_I
P30530 N266D - 226 321 fn3
P30685 F91S - 25 203 MHC_I
P30685 Y98D - 25 203 MHC_I
P31358 I41M - 21 61 CD52
P32004 W276R - 239 316 Ig_3
P32004 I645P - 613 701 fn3
P32004 W754R - 716 800 fn3
P35475 H449N - 23 543 Glyco_hydro_39
P35556 L2581S - 2571 2612 EGF_CA
P35558 M60T - 29 256 PEPCK_N
P35573 A1207T - 1042 1527 GDE_C
P35579 V967E - 841 1921 Myosin_tail_1
P35749 V1310M - 848 1928 Myosin_tail_1
P41217 V76G - 36 136 ig
P42127 Q61P - 42 128 Agouti
P42226 M181R - 162 271 STAT_alpha
P43628 L32R - 32 115 ig
P45379 I221T - 103 240 Troponin
P46013 V1559M - 1488 1598 K167R
P48448 H203R - 3 347 Aldedh
P49790 I248V - 113 621 Nup153
P51587 I2490T - 2481 2667 BRCA-2_helical
P52655 A109P - 13 270 TFIIA
P52701 Y538S - 537 703 MutS_II
P54132 K137R - 1 367 BLM_N
P54315 L461P - 358 465 PLAT
P54652 C191S - 7 615 HSP70
55 UniProt Mutation Disease Start End Domain
P55056 L36P - 31 124 APOC4
P55851 R154Q - 112 208 Mito_carr
P60014 C126S - 114 162 Keratin_B2_2
P60368 R241G - 197 255 Keratin_B2_2
P68871 L49P - 8 112 Globin
P68871 F72S - 8 112 Globin
P68871 V68G - 8 112 Globin
P69892 K9E - 8 112 Globin
P69905 W15R - 7 107 Globin
P69905 A80G - 7 107 Globin
P78324 V132T - 38 145 V-set
Q00G26 C255R - 16 368 Perilipin
Q01518 Y249D - 5 295 CAP_N
Q02548 V26G - 16 140 PAX
Q03395 R242Q - 17 290 Tetraspannin
Q04826 C349S - 337 362 MHC_I_C
Q12879 E1426K - 839 1464 NMDAR2_C
Q13751 N181D - 26 248 Laminin_N
Q13936 A1365T - 1320 1535 Ion_trans
Q13936 A1765G - 1701 1996 CAC1F_C
Q14517 N1330S - 1261 1344 Cadherin
Q14517 R902S - 827 918 Cadherin
Q14524 D596G - 478 667 Na_trans_cytopl
Q15003 V539A - 27 739 Cnd2
Q15436 L211V - 126 390 Sec23_trunk
Q15661 R216Q - 31 267 Trypsin
Q15928 K358N - 339 361 zf-C2H2
Q16352 T92S - 10 92 Filament_head
Q16363 Y498H - 298 555 Laminin_I
Q16600 C209G - 207 229 zf-C2H2
Q16654 D109G - 34 195 BCDHK_Adom3
Q29865 A97T - 25 203 MHC_I
Q29980 D105G - 24 201 MHC_I
Q29983 W253S - 208 289 C1-set
Q2TB90 D54G - 21 219 Hexokinase_1
Q2VPA4 L491P - 475 541 Sushi
Q31610 C349S - 337 362 MHC_I_C
Q53EL9 T546A - 532 589 Sushi
Q53F39 A268P - 70 307 Metallophos
Q59H18 I686T - 463 719 Pkinase_Tyr
Q5H8C1 Q2143P - 2071 2177 Lectin_C
56 UniProt Mutation Disease Start End Domain
Q5H8C1 V2174G - 2071 2177 Lectin_C
Q5JRX3 A554D - 504 752 M16C_assoc
Q5T1N1 L352V - 327 421 AKNA
Q5T8A7 V98A - 1 852 PPP1R26_N
Q5TAP6 R319H - 22 734 Utp14
Q5W0U4 A261P - 232 281 PRY
Q63ZY6 W47S - 35 239 Methyltr_RsmB-F
Q6IEE7 R420Q - 359 705 TMEM132
Q6N021 V1900A - 1290 1905 Tet_JBP
Q6P1J9 L384P - 356 521 CDC73_C
Q6P1W5 Y438H - 199 598 DUF4688
Q6P387 Y335H - 1 395 DUF4529
Q6QNK2 G140S - 88 241 Laminin_G_3
Q6T423 R300T - 140 484 MFS_1
Q6UWX4 R394Q - 216 552 GSDH
Q6UXB8 T50P - 37 165 CAP
Q6V1P9 N897S - 848 939 Cadherin
Q6V1P9 E1595Q - 1589 1676 Cadherin
Q6ZMU1 D251G - 168 335 A2M_comp
Q6ZN55 R785Q - 766 788 zf-C2H2
Q7Z3T1 C169S - 31 308 7tm_4
Q7Z3V5 L573H - 558 580 zf-C2H2
Q7Z3Y8 I305T - 83 398 Filament
Q7Z3Z2 W6R - 5 133 RD3
Q7Z4T9 S253T - 191 343 PaaSYMP
Q7Z5B4 C130Y - 15 166 RIC3
Q7Z5Q5 S502G - 447 854 DNA_pol_A
Q7Z6I6 F70L - 34 186 RhoGAP
Q7Z6M1 R60G - 30 82 Kelch_2
Q86TZ1 I87S - 58 88 TPR_8
Q86UT8 W244G - 6 323 CCDC84
Q86WI1 Y440H - 340 490 PA14
Q8IUC1 C111S - 1 163 PMG
Q8IVS2 A303G - 64 346 Acyl_transf_1
Q8IWW8 C449R - 52 456 Fe-ADH
Q8IY42 A151T - 9 314 DUF4699
Q8IYA6 L614S - 423 660 CKAP2_C
Q8IYB9 A628G - 620 642 zf-C2H2
Q8IYL3 A101S - 6 237 UPF0688
Q8IYX0 C223S - 212 235 zf-C2H2_4
Q8N149 V331G - 327 409 ig
57 UniProt Mutation Disease Start End Domain
Q8N6C8 L107R - 28 118 Ig_2
Q8N7X0 I310T - 178 319 Peptidase_C2
Q8N9C0 A94P - 67 157 I-set
Q8N9Y4 L162M - 63 342 FAM181
Q8NA69 Y396N - 66 504 DUF4601
Q8NA69 Y434N - 66 504 DUF4601
Q8NDH2 G264S - 250 385 CCDC168_N
Q8NG57 L375P - 352 450 Elongin_A
Q8NI35 A1504P - 1435 1517 PDZ
Q8TAL5 D252G - 1 454 DUF4647
Q8TDX9 D812N - 702 1325 REJ
Q8WZ42 V3250G - 3239 3328 I-set
Q8WZ42 D13469N - 13390 13475 I-set
Q8WZ42 A18222T - 18149 18233 I-set
Q8WZ42 L22408P - 22388 22478 I-set
Q8WZ42 G30887S - 30860 30945 fn3
Q95365 C91S - 25 203 MHC_I
Q95604 A97T - 25 203 MHC_I
Q969T4 W201R - 65 202 UQ_con
Q969Y2 V250A - 155 489 MnmE_helical
Q969Y2 A322P - 251 375 MMR_HSR1
Q96BZ9 N79S - 63 266 RabGAP-TBC
Q96DW6 R66G - 24 119 Mito_carr
Q96EG1 R326G - 36 378 Sulfatase
Q96FT9 R85H - 63 193 IFT43
Q96KP4 Y126H - 95 469 Peptidase_M20
Q96LK8 V142M - 138 383 VAD1-2
Q96LU7 L845M - 768 909 MRF_C2
Q96LW9 T50S - 35 124 SCAN
Q96M86 I4666T - 3977 4749 Dynein_heavy
Q96PL5 C259R - 240 288 PRY
Q96PL5 G263E - 240 288 PRY
Q96SK3 A653P - 645 667 zf-C2H2
Q96T68 V473M - 378 694 SET
Q99518 F182S - 2 471 FMO-like
Q99593 A143T - 56 238 T-box
Q99895 D35H - 30 262 Trypsin
Q99895 D35N - 30 262 Trypsin
Q9BUV0 Y147H - 1 290 RSRP
Q9BVL2 S166P - 3 599 Nucleoporin_FG2
Q9BWX5 Y16D - 1 176 GATA-N
58 UniProt Mutation Disease Start End Domain
Q9BWX5 Y142H - 1 176 GATA-N
Q9BXM7 L461S - 264 509 Pkinase
Q9BYD6 F177S - 50 301 Ribosomal_L1
Q9GIY3 A86S - 42 116 MHC_II_beta
Q9H078 R295T - 240 326 Ank_2
Q9H0R5 C491R - 282 578 GBP_C
Q9H0R5 V558A - 282 578 GBP_C
Q9H1E1 A103P - 34 153 RnaseA
Q9H251 A1443G - 1424 1518 Cadherin
Q9H324 T134S - 40 180 Pep_M12B_propep
Q9HA65 L99P - 3 218 DUF3548
Q9HB63 Y205H - 34 260 Laminin_N
Q9NP86 I147S - 107 172 EF-hand_7
Q9NP92 C33S - 1 429 PDCD9
Q9NQ11 V578G - 507 788 Hydrolase
Q9NQ36 T791S - 757 804 Ephrin_rec_like
Q9NR63 A420G - 50 490 p450
Q9NRC6 R1367T - 1314 1417 Spectrin
Q9NRH2 L260S - 16 269 Pkinase
Q9NS87 E1272D - 1265 1388 HMMR_C
Q9NTJ4 V950M - 622 1032 Glyco_hydro_38C
Q9NX24 A118T - 45 139 Ribosomal_L7Ae
Q9NYA4 S280G - 127 519 Myotub-related
Q9NYA4 V297G - 127 519 Myotub-related
Q9NYK6 D136E - 1 291 EURL
Q9NZT1 S58G - 10 74 EF-hand_7
Q9P003 A3G - 3 130 Cornichon
Q9P2K9 A650T - 412 780 Patched
Q9P2T0 R267Q - 217 275 THEG
Q9P2W1 Y163N - 11 181 TBPIP
Q9UBB9 N177S - 149 193 G-patch
Q9UBZ9 A1003T - 938 1073 DUF4414
Q9UHC7 V439A - 400 480 MKRN1_C
Q9UJW8 W89C - 71 112 KRAB
Q9UJZ1 L129P - 39 257 Band_7
Q9UKQ2 N493S - 493 591 ADAM_CR
Q9ULD4 A278G - 267 386 zf-HC5HC2H_2
Q9UM07 M164T - 113 273 PAD_M
Q9UN36 T45S - 40 318 Ndr
Q9UP65 R148G - 44 250 PLA2_B
Q9UPM9 S51P - 11 174 B9-C2
59 UniProt Mutation Disease Start End Domain
Q9UPR6 I718M - 658 904 DZF
Q9UQ90 R688Q - 541 746 Peptidase_M41
Q9UQF0 V129A - 56 477 TLV_coat
Q9Y2E5 Q243P - 28 351 Glyco_hydro_38
Q9Y2Z9 V406M - 328 427 FAD_binding_3
Q9Y3M9 R467G - 460 482 zf-C2H2
Q9Y3S2 T28A - 1 300 NOA36
Q9Y473 Y363N - 363 385 zf-C2H2
Q9Y5E8 R494Q - 456 552 Cadherin
Q9Y5G6 E188G - 138 233 Cadherin
Q9Y5H8 I318V - 247 341 Cadherin
Q9Y5W8 L472S - 373 512 RGS
Q9Y623 I1106M - 847 1928 Myosin_tail_1
Q9Y6H6 R99H - 20 101 ISK_Channel
60 Table S9 Cleavage sites within 15 residues of disease-associated DO mutations
Cleavage Cleavage UniProt/dbSNP Mutation Motifa Peptidase Evidencec position typeb P63267/- P110L 106 PTLL†TEALLNP HtrA2 peptidase P MS P63267/- P110L 107 TLLT†EALLNP HtrA2 peptidase P MS GAHG†RGHREDFRFCSQ Q9Y653/rs121908462 R38W 25 unknown peptidase P NT WNQT CAVA†QHAPPWTEDCR Q13510/rs137853595 Y36C 21 unknown peptidase P NT KSTCPPS NVTWPAAQPSF†HQA matrix O95817/rs397514506 R218W 225 N MS metallopeptidase-2 P22748/rs104894559 R14W 18 SAAWPSAS†AES unknown peptidase P NT KVVGKIDVCPENAEVTL P49747/- D515G 530 ADAMTS4 peptidase P MS TD†FRA P35222/rs28931588 D32Y 32 SYLY†SGI caspase-3 P - P35222/rs121913400 S33F 32 SYLD†FGIH caspase-3 P - P35222/rs121913400 S33Y 32 SYLD†YGIH caspase-3 P - P35222/rs121913403 S37C 32 SYLD†SGIHCGAT caspase-3 P - P35222/rs121913403 S37F 32 SYLD†SGIHFGAT caspase-3 P - LSAR†VVVGED kallikrein-related Q99895/- G32V 29 P CS peptidase 4 VSEE†SNVLCLSKSHNK P13639/rs587777052 P596H 586 unknown peptidase P NT H P13639/rs587777052 P596H 594 CLSK†SHNKH trypsin 1 N MS P13639/rs587777052 P596H 601 SKSHNKHNR†LYM DESC1 peptidase N MS SKSHNKHNRLYMK†AR P13639/rs587777052 P596H 605 unknown peptidase P NT P SKSHNKHNRLYMKARP granzyme B (Homo P13639/rs587777052 P596H 611 P MS FPD†GLA sapiens-type) P00742/rs104894392 R366C 370 GFGCTHEK†GRQ plasmin P - P00742/rs104894392 R366C 372 GFGCTHEKGR†QST coagulation factor Xa P - P00734/rs121918477 R314C 314 IEGC†TAT coagulation factor Xa P - P00734/rs121918477 R314C 314 IEGC†TAT lumbrokinase N NT P00734/rs121918477 R314C 315 IEGCT†ATS vibriolysin N NT IEGCTATSEYQTFFNPR† P00734/rs121918477 R314C 327 coagulation factor Xa P - TFG IEGCTATSEYQTFFNPR† P00734/rs121918477 R314C 327 thrombin P - TFG IEGCTATSEYQTFFNPR† mannan-binding lectin- P00734/rs121918477 R314C 327 TFG associated serine P NT peptidase 2 IEGCTATSEYQTFFNPR† P00734/rs121918477 R314C 327 lumbrokinase N NT TFG IEGCTATSEYQTFFNPR† kallikrein-related P00734/rs121918477 R314C 327 P CS TFG peptidase 4 IEGCTATSEYQTFFNPR† P00734/rs121918477 R314C 327 pseutarin C P - TFG P00451/rs111033613 R1708C 1708 QSPC†SFQ coagulation factor Xa P - P00451/rs111033613 R1708C 1708 QSPC†SFQ thrombin P - P00451/rs111033613 R1708C 1708 QSPC†SFQ plasmin P NT P35555/rs61746008 R2726W 2731 YPKWGRKRR†STN furin P - P35555/rs61746008 R2726W 2731 YPKWGRKRR†STN PCSK2 peptidase N CS P35555/rs61746008 R2726W 2731 YPKWGRKRR†STN PCSK4 peptidase N CS P35555/rs61746008 R2726W 2731 YPKWGRKRR†STN PCSK6 peptidase N CS P35555/rs61746008 R2726W 2731 YPKWGRKRR†STN PCSK5 peptidase N CS P35555/rs61746008 R2726W 2731 YPKWGRKRR†STN PCSK7 peptidase N CS
61 Cleavage Cleavage UniProt/dbSNP Mutation Motifa Peptidase Evidencec position typeb DSGE†GDFLAEGGGVCG P02671/rs121909606 R35C 24 ecp peptidase N - PR EGDF†LAEGGGVCGPR matrix P02671/rs121909606 R35C 27 P NT metallopeptidase-7 GGVC†GPR matrix P02671/rs121909606 R35C 35 P NT metallopeptidase-3 GGVC†GPR matrix P02671/rs121909606 R35C 35 P NT metallopeptidase-7 GGVC†GPR membrane-type matrix P02671/rs121909606 R35C 35 P NT metallopeptidase-1 P02671/rs121909606 R35C 35 GGVC†GPR crotalase N - P02671/rs121909606 R35C 35 GGVC†GPR bothrombin N - P02671/rs121909606 R35C 35 GGVC†GPR thrombin P - P02671/rs121909606 R35C 35 GGVC†GPR plasmin P - GGVC†GPR rhombeobin (Lachesis P02671/rs121909606 R35C 35 P NT muta rhombeata ) P02671/rs121909606 R35C 35 GGVC†GPR kangshuanmei peptidase P NT GGVC†GPR coagulant peptidase P02671/rs121909606 R35C 35 (Trimeresurus P - flavoviridis) GGVCGPR†VVE matrix P02671/rs121909606 R35C 38 P NT metallopeptidase-3 GGVCGPR†VVE matrix P02671/rs121909606 R35C 38 P NT metallopeptidase-7 GGVCGPR†VVE kallikrein-related P02671/rs121909606 R35C 38 P - peptidase 14 P02671/rs121909606 R35C 38 GGVCGPR†VVE plasmin P - GGVCGPRVVE†RHQ ulilysin P02671/rs121909606 R35C 41 (Methanosarcina N - acetivorans) P21333/rs137853319 P1291L 1283 VDAR†ALTQTGGLHVK trypsin 1 N MS P35637/rs186547381 P431L 424 QRAG†DWKCPNLTCE meprin alpha subunit N MS P35637/rs186547381 P431L 424 QRAG†DWKCPNLTCE meprin beta subunit N MS P48506/- P158L 156 PGFT†LLEVK cathepsin L N MS DLTD†AAARNAELLLQA P14136/rs121909719 R276L 266 caspase-3 P CS K NYNVFGNYNQQPS†NY P22626/rs397515326 D302V 311 granzyme M N MS G LVTCSY†LLG farnesylated-protein P02545/rs142000963 R644C 646 P MU converting enzyme 1 P02545/rs121912496 R249W 252 QELWAQH†EDQ meprin alpha subunit N MS P02545/rs121912496 R249W 252 QELWAQH†EDQ meprin beta subunit N MS P02545/rs121912496 R249W 253 QELWAQHE†DQV meprin alpha subunit N MS P02545/rs121912496 R249W 253 QELWAQHE†DQV meprin beta subunit N MS P10636/rs63751273 P618L 627 KHVLGGGSVQIVY†KPV calpain-2 P - SALS†SASTSSHNLQCIF P43243/rs121434591 S85C 74 cathepsin S N MS N DTLD†STAAQQELRSKC P35579/rs80338829 R1165C 1153 caspase-3 P MS EQE DTLD†STAAQQELRSKC P35579/rs80338829 R1165C 1153 caspase-6 P MS EQE DTLD†STAAQQELRSKC P35579/rs80338829 R1165C 1153 caspase-2 P MS EQE P35579/rs80338829 R1165C 1162 QELR†SKCEQE trypsin 1 N MS P35579/rs80338829 R1165C 1165 RSKC†EQE trypsin 1 N MS P35579/rs80338829 R1165C 1173 RSKCEQEVNILK†KTL trypsin 1 N MS
62 Cleavage Cleavage UniProt/dbSNP Mutation Motifa Peptidase Evidencec position typeb DTLD†STAAQQELRSKL P35579/rs80338830 R1165L 1153 caspase-3 P MS EQE DTLD†STAAQQELRSKL P35579/rs80338830 R1165L 1153 caspase-6 P MS EQE DTLD†STAAQQELRSKL P35579/rs80338830 R1165L 1153 caspase-2 P MS EQE P35579/rs80338830 R1165L 1162 QELR†SKLEQE trypsin 1 N MS P35579/rs80338830 R1165L 1165 RSKL†EQE trypsin 1 N MS P35579/rs80338830 R1165L 1173 RSKLEQEVNILK†KTL trypsin 1 N MS P35579/rs80338831 D1424Y 1423 QELD†YLLV meprin alpha subunit N MS QELD†YLLV LAST_MAM peptidase P35579/rs80338831 D1424Y 1423 N MS (Limulus-type) LPTY†EHIQTALSSKDRR Q10713/rs869025293 G515R 503 meprin beta subunit N MS LP PTYE†HIQTALSSKDRRL glutamyl endopeptidase Q10713/rs869025293 G515R 504 N MS P I RSHL†KRDTEDQEDQVD P04070/rs121918145 P210L 197 unknown peptidase P NT LRLI HLKR†DTEDQEDQVDLR P04070/rs121918145 P210L 199 furin P - LI HLKR†DTEDQEDQVDLR P04070/rs121918145 P210L 199 PCSK2 peptidase N CS LI HLKR†DTEDQEDQVDLR P04070/rs121918145 P210L 199 PCSK4 peptidase N CS LI HLKR†DTEDQEDQVDLR P04070/rs121918145 P210L 199 PCSK6 peptidase N CS LI HLKR†DTEDQEDQVDLR P04070/rs121918145 P210L 199 PCSK5 peptidase N CS LI HLKR†DTEDQEDQVDLR P04070/rs121918145 P210L 199 PCSK7 peptidase N CS LI P04070/rs121918145 P210L 211 QVDLR†LID thrombin P - QVDLR†LID kallikrein-related P04070/rs121918145 P210L 211 P CS peptidase 4 RKRR†ANSLLEETKQDN kallikrein-related P07225/- G52D 41 P CS LE peptidase 4 O43395/rs121434242 P493S 485 MRVL†GTEAVQDSTKV granzyme M P MS P06400/- N803K 810 PGGKIYISPLK†SPY calpain-2 N - ERHHVHLRSATLRDAVP RC1339 g.p. (Rickettsia Q8TDP1/rs75328625 R13H 27 N MS A†TLH conorii) KESWGAHAREDYKVRI P31040/rs387906780 R589W 604 meprin beta subunit N MS DEY†DYS Q15465/rs28936675 G31R 23 SGLA†CGPGRGFRKRR unknown peptidase P NT Q15465/rs752650571 G196E 197 AKSEG†CFP Sonic hedgehog protein N - LLLT†AAHLLFVAPHND Q15465/- S280W 267 unknown peptidase P NT WATG TAAH†LLFVAPHNDWA Q15465/- S280W 270 unknown peptidase P NT TG P17405/- G242R 251 PGARYWGEYSKCD†LPL caspase-7 P MU SGDH†CIIGRTLVVHEKA matrix P00441/- D125V 111 N MS VDLG metallopeptidase-2 GDHC†IIGRTLVVHEKA matrix P00441/- D125V 112 N MS VDLG metallopeptidase-2 P00441/- D125V 116 IIGR†TLVVHEKAVDLG trypsin 1 N MS VVHE†KAVDLG glutamyl endopeptidase P00441/- D125V 122 N MS I P00441/- D125V 125 EKAV†DLG meprin alpha subunit N MS VVRLCPHHERCSDSD†G P04637/rs28934578 R175L 186 caspase-3 P - LA
63 Cleavage Cleavage UniProt/dbSNP Mutation Motifa Peptidase Evidencec position typeb YSEVLKDAQEKLELAEK P09493/rs199476306 A63V 77 trypsin 1 N MS K†ATD FVHW†YVGEGMEEGEF Q71U36/rs137853047 S419L 407 HtrA2 peptidase P MS LEAR Q71U36/rs137853047 S419L 413 GEGM†EEGEFLEAR HtrA2 peptidase P MS Q71U36/rs137853047 S419L 422 GEFLEAR†EDM trypsin 1 N MS GEFLEAREDMAALEK†D Q71U36/rs137853047 S419L 430 trypsin 1 N MS YE GEFLEAREDMAALEKD† granzyme B (Homo Q71U36/rs137853047 S419L 431 P MS YEE sapiens-type)
aMotif: the motif contains the mutation (bold and italic) and the cleavage position (†) from the MEROPS database [4]. bCleavage type. N: Peptide and protein substrates that are not physiologically relevant are indicated; P: Peptide and protein substrates that are thought to be physiologically relevant are indicated. cEvidence. MS: mass spectroscopy; NT: N-terminal sequencing.
64 Table S10. Top 10 frequently observed mutation patterns of (A) DO, (B) OD, (C) OO and (D) DD transitions for both disease-associated and non-disease mutations/polymorphisms.
(A) DO Disease-associated mutation Polymorphism Mutation pattern Number of mutations Mutation pattern Number of mutations RW 59(11.5%) PL 153(12.56%) PL 48(9.36%) RC 80(6.57%) RC 45(8.77%) RW 80(6.57%) GR 36(7.02%) AV 65(5.34%) GD 19(3.70%) SL 57(4.68%) GV 19(3.70%) TI 46(3.78%) SF 17(3.31%) GR 42(3.45%) SL 17(3.31%) SF 35(2.87%) TI 16(3.12%) RL 28(2.30%) AV 13(2.53%) PA 27(2.22%)
(B) OD Disease-associated mutation Polymorphism Mutation pattern Number of mutations Mutation pattern Number of mutations LP 108(16.62%) LP 63(7.79%) CR 38(5.85%) AT 40(4.94%) CS 29(4.46%) IT 39(4.82%) WR 25(3.85%) VM 32(3.96%) RP 25(3.85%) RG 30(3.71%) CG 24(3.69%) CS 30(3.71%) IT 22(3.38%) VA 29(3.58%) FS 21(3.32%) AG 28(3.46%) LR 19(2.92%) CR 26(3.21%) VG 19(2.92%) RQ 24(2.97%)
(C) OO Disease-associated mutation Polymorphism Mutation pattern Number of mutations Mutation pattern Number of mutations LP 909(3.67%) VI 934(3.52%) RC 905(3.66%) AT 878(3.31%) GR 843(3.40%) RQ 873(3.29%) RW 785(3.17%) RH 791(2.98%) RQ 756(3.05%) IV 771(2.90%) RH 729(2.94%) AV 709(2.67%) EK 634(2.56%) VM 588(2.21%) PL 570(2.30%) RC 558(2.10%) YC 513(2.07%) EK 549(2.07%) CY 488(1.97%) TA 474(1.78%)
65
(D) DD Disease-associated mutation Polymorphism Mutation pattern Number of mutations Mutation pattern Number of mutations GR 228(8.32%) AT 381(3.42%) GD 142(5.18%) PL 379(3.40%) GS 141(5.14%) PS 362(3.24%) GV 110(4.01%) RQ 322(2.89%) RQ 106(3.87%) AV 290(2.60%) GE 100(3.65%) RH 269(2.42%) EK 97(3.54%) TA 267(2.40%) RH 88(3.21%) GS 246(2.21%) PL 69(2.52%) EK 241(2.16%) GC 67(2.44%) GR 214(1.92%)
66 Table S11. Mutations and polymorphisms located in experimentally-verified LDRsa
#OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors O15273/- Telethonin #91-167 E132Q - 3
O15273/rs773317399 Telethonin #91-167 T137I Cardiomyopathy; familial hypertrophic 25 (CMH25) [MIM:607487] 3 P00736/- Complement C1r subcomponent #193-305 D290G Ehlers-Danlos syndrome; periodontal type; 1 (EDSPD1) [MIM:130080] 3^ P00736/- Complement C1r subcomponent #193-305 G297D Ehlers-Danlos syndrome; periodontal type; 1 (EDSPD1) [MIM:130080] 4 P00736/- Complement C1r subcomponent #193-305 L300P Ehlers-Danlos syndrome; periodontal type; 1 (EDSPD1) [MIM:130080] 3^ P00736/- Complement C1r subcomponent #193-305 R301P Ehlers-Danlos syndrome; periodontal type; 1 (EDSPD1) [MIM:130080] 4 P00736/- Complement C1r subcomponent #193-305 Y302C Ehlers-Danlos syndrome; periodontal type; 1 (EDSPD1) [MIM:130080] 4 P00736/rs3813728 Complement C1r subcomponent #193-305 G261R - 4 P01106/rs121918685 Myc proto-oncogene protein #1-88 P59A A Burkitt lymphoma sample 2^ P01106/rs121918685 Myc proto-oncogene protein #1-167 P59A A Burkitt lymphoma sample 2^ P01106/rs121918685 Myc proto-oncogene protein #1-143 P59A A Burkitt lymphoma sample 2^ P01106/rs28933407 Myc proto-oncogene protein #1-88 P57S A Burkitt lymphoma sample 2^ P01106/rs28933407 Myc proto-oncogene protein #1-167 P57S A Burkitt lymphoma sample 2^ P01106/rs28933407 Myc proto-oncogene protein #1-143 P57S A Burkitt lymphoma sample 2^ P01106/rs4645959 Myc proto-oncogene protein #1-88 N11S - 3^ P01106/rs4645959 Myc proto-oncogene protein #1-167 N11S - 3^ P01106/rs4645959 Myc proto-oncogene protein #1-143 N11S - 3^ P01112/rs121913233 GTPase HRas #58-66 Q61L Melanoma 4 P01112/rs121913233 GTPase HRas #59-65 Q61L Melanoma 4 P01112/rs121913233 GTPase HRas #59-67 Q61L Melanoma 4 Congenital myopathy with excess of muscle spindles (CMEMS) P01112/rs121917756 GTPase HRas #58-66 E63K [MIM:218040] 3 Congenital myopathy with excess of muscle spindles (CMEMS) P01112/rs121917756 GTPase HRas #59-65 E63K [MIM:218040] 3 Congenital myopathy with excess of muscle spindles (CMEMS) P01112/rs121917756 GTPase HRas #59-67 E63K [MIM:218040] 3
67 #OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors P01112/rs121917758 GTPase HRas #58-66 T58I Costello syndrome (CSTLO) [MIM:218040] 4 P01112/rs28933406 GTPase HRas #58-66 Q61K Thyroid cancer; non-medullary; 2 (NMTC2) [MIM:188470] 3 P01112/rs28933406 GTPase HRas #59-65 Q61K Thyroid cancer; non-medullary; 2 (NMTC2) [MIM:188470] 3 P01112/rs28933406 GTPase HRas #59-67 Q61K Thyroid cancer; non-medullary; 2 (NMTC2) [MIM:188470] 3 P02545/- Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 K515E Lipodystrophy; familial partial; 2 (FPLD2) [MIM:151660] 3 P02545/rs11575937 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R482L Lipodystrophy; familial partial; 2 (FPLD2) [MIM:151660] 4 P02545/rs11575937 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R482Q Lipodystrophy; familial partial; 2 (FPLD2) [MIM:151660] 3 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs142000963 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R644C [MIM:181350] 3 P02545/rs201583907 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 G523R Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 4 P02545/rs267607607 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 T488P - 3^ Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs267607642 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 D461Y [MIM:181350] 2^ P02545/rs28928902 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R471C Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670] 4 P02545/rs56673169 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 K542N Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670] 3 P02545/rs56984562 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R541C - 4 P02545/rs56984562 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R541S Cardiomyopathy; dilated 1A (CMD1A) [MIM:115200] 3^ P02545/rs57318642 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R527C Hutchinson-Gilford progeria syndrome (HGPS) [MIM:176670] 4 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs57520892 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R527P [MIM:181350] 3 Mandibuloacral dysplasia with type A lipodystrophy (MADA) P02545/rs57520892 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R527H [MIM:248370] 4 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs57629361 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 T528K [MIM:181350] 4 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs57629361 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 T528R [MIM:181350] 4 P02545/rs57830985 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R582H Lipodystrophy; familial partial; 2 (FPLD2) [MIM:151660] 2^ P02545/rs57920071 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R482W Lipodystrophy; familial partial; 2 (FPLD2) [MIM:151660] 4 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs58362413 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 W520S [MIM:181350] 3^
68 #OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs58541611 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 D446V [MIM:181350] 3 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs58932704 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R453W [MIM:181350] 3 P02545/rs59981161 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 K486N Lipodystrophy; familial partial; 2 (FPLD2) [MIM:151660] 4 Mandibuloacral dysplasia with type A lipodystrophy (MADA) P02545/rs60580541 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 A529V [MIM:248370] 4 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs60934003 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 L530P [MIM:181350] 2^ Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs60992550 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 N456I [MIM:181350] 3 P02545/rs61224243 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 E578V - 2^ Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs61444459 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R541H [MIM:181350] 4 Emery-Dreifuss muscular dystrophy 2; autosomal dominant (EDMD2) P02545/rs61444459 Prelamin-A/C [Cleaved into: Lamin-A/C #386-664 R541P [MIM:181350] 3^ P02788/rs1126478 Lactotransferrin #38-59 K47R - 2^ P03372/rs139960913 Estrogen receptor #1-184 H6Y A breast cancer sample 2^ P04150/- Glucocorticoid receptor #77-262 D233N - 2^ P04150/rs542110718 Glucocorticoid receptor #77-262 L112F - 2^ P04156/rs16990018 Major prion protein #167-171 N171S - 3^ P04156/rs74315402 Major prion protein #23-124 A117V - 4 T-cell surface glycoprotein CD3 delta P04234/rs45510201 chain #127-171 Q147R - 4 P05121/rs6090 Plasminogen activator inhibitor 1 #1-23 V17I - 4 P05121/rs6092 Plasminogen activator inhibitor 1 #1-23 A15T - 4 Gaucher disease; atypical; due to saposin C deficiency (AGD) P07602/- Prosaposin #385-391 C388F [MIM:610539] 4 Gaucher disease; atypical; due to saposin C deficiency (AGD) P07602/rs121918110 Prosaposin #346-353 L349P [MIM:610539] 2^ Gaucher disease; atypical; due to saposin C deficiency (AGD) P07602/rs121918110 Prosaposin #330-377 L349P [MIM:610539] 2^ P10275/- Androgen receptor #654-670 I665N Androgen insensitivity; partial (PAIS) [MIM:312300] 2^
69 #OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors P10275/- Androgen receptor #142-485 Q445R Androgen insensitivity syndrome (AIS) [MIM:300068] 2^ P10275/- Androgen receptor #142-485 M268T Prostate cancer 4 P10275/- Androgen receptor #142-485 P271S Prostate cancer 3^ P10275/- Androgen receptor #844-849 R847G Prostate cancer 3^ P10275/rs138454018 Androgen receptor #142-485 P342L Prostate cancer 3 P10275/rs201934623 Androgen receptor #142-485 P392S Androgen insensitivity syndrome (AIS) [MIM:300068] 2^ P10275/rs773996740 Androgen receptor #142-485 P392R Androgen insensitivity syndrome (AIS) [MIM:300068] 2^ P10912/rs6180 Growth hormone receptor #270-620 I544L - 4 P10912/rs6183 Growth hormone receptor #270-620 P495T - 3^ P11387/rs6029542 DNA topoisomerase 1 #175-214 G214S - 2^ Cystic fibrosis transmembrane Congenital bilateral absence of the vas deferens (CBAVD) P13569/rs1800103 conductance regulator #708-831 I807M [MIM:277180] 3 Cystic fibrosis transmembrane Congenital bilateral absence of the vas deferens (CBAVD) P13569/rs397508363 conductance regulator #708-831 R766M [MIM:277180] 2^ Cystic fibrosis transmembrane P13569/rs397508378 conductance regulator #708-831 E822K Cystic fibrosis (CF) [MIM:219700] 2^ Cystic fibrosis transmembrane P13569/rs397508381 conductance regulator #708-831 E826K - 3 Potassium voltage-gated channel P15382/rs1805128 subfamily E member 1 #72-91 D85N - 4 Potassium voltage-gated channel P15382/rs199473350 subfamily E member 1 #24-45 S28L Long QT syndrome 5 (LQT5) [MIM:613695] 2^ Potassium voltage-gated channel P15382/rs199473360 subfamily E member 1 #72-91 E83K Long QT syndrome 5 (LQT5) [MIM:613695] 4 Potassium voltage-gated channel P15382/rs199473361 subfamily E member 1 #72-91 W87R Long QT syndrome 5 (LQT5) [MIM:613695] 2^ Potassium voltage-gated channel P15382/rs74315445 subfamily E member 1 #72-91 D76N Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347] 3^ Potassium voltage-gated channel P15382/rs74315446 subfamily E member 1 #72-91 S74L Long QT syndrome 5 (LQT5) [MIM:613695] 4 Potassium voltage-gated channel P15382/rs77442996 subfamily E member 1 #107-129 V109I Long QT syndrome 5 (LQT5) [MIM:613695] 4 #1362- P25054/rs137854578 Adenomatous polyposis coli protein 1745 S1395C - 3
70 #OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors P30291/rs34412975 Wee1-like protein kinase #1-292 G210C - 3 #1144- Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS) P32004/- Neural cell adhesion molecule L1 1257 S1224L [MIM:307000] 4 P35611/rs4962 Alpha-adducin #430-737 N510I - 3 P35612/rs17855969 Beta-adducin #409-726 T439A - 3^ P35869/rs2066853 Aryl hydrocarbon receptor #545-713 R554K - 4 P35869/rs4986826 Aryl hydrocarbon receptor #545-713 V570I - 4 Peroxisome proliferator-activated receptor P37231/rs1800571 gamma #112-174 P113Q Obesity (OBESITY) [MIM:601665] 2^ Peroxisome proliferator-activated receptor P37231/rs1805192 gamma #9-111 P40A - 4 P37840/rs104893875 Alpha-synuclein #1-140 E46K Dementia Lewy body (DLB) [MIM:127750] 2^ P37840/rs104893875 Alpha-synuclein #1-113 E46K Dementia Lewy body (DLB) [MIM:127750] 2^ P37840/rs104893875 Alpha-synuclein #42-92 E46K Dementia Lewy body (DLB) [MIM:127750] 2^ P37840/rs104893875 Alpha-synuclein #1-102 E46K Dementia Lewy body (DLB) [MIM:127750] 2^ #103- P38398/- Breast cancer type 1 susceptibility protein 1646 S1187I Breast cancer (BC) [MIM:114480] 2^ #103- P38398/- Breast cancer type 1 susceptibility protein 1646 S1217Y Breast cancer (BC) [MIM:114480] 2^ #103- P38398/- Breast cancer type 1 susceptibility protein 1646 R866Q Breast cancer (BC) [MIM:114480] 2^ #103- P38398/- Breast cancer type 1 susceptibility protein 1646 F1226L Breast-ovarian cancer; familial; 1 (BROVCA1) [MIM:604370] 3 #103- P38398/- Breast cancer type 1 susceptibility protein 1646 S1297P Breast cancer (BC) [MIM:114480] 2^ #103- P38398/- Breast cancer type 1 susceptibility protein 1646 G778C A breast cancer sample 3 #103- P38398/rs273900719 Breast cancer type 1 susceptibility protein 1646 S1301R Breast cancer (BC) [MIM:114480] 2^ #103- P38398/rs28897673 Breast cancer type 1 susceptibility protein 1646 Y105C - 4 #103- P38398/rs28897682 Breast cancer type 1 susceptibility protein 1646 N810Y Breast cancer (BC) [MIM:114480] 4 #103- P38398/rs28897687 Breast cancer type 1 susceptibility protein 1646 N1236K Breast cancer (BC) [MIM:114480] 2^
71 #OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors #103- P38398/rs397509022 Breast cancer type 1 susceptibility protein 1646 G960D Breast cancer (BC) [MIM:114480] 3^ #103- P38398/rs397509034 Breast cancer type 1 susceptibility protein 1646 T1025I Breast cancer (BC) [MIM:114480] 3 #103- P38398/rs41286300 Breast cancer type 1 susceptibility protein 1646 R866C - 3 #103- P38398/rs4986847 Breast cancer type 1 susceptibility protein 1646 I925L - 2^ #103- P38398/rs4986848 Breast cancer type 1 susceptibility protein 1646 F989S - 2^ #103- P38398/rs55688530 Breast cancer type 1 susceptibility protein 1646 S186Y Breast cancer (BC) [MIM:114480] 3^ #103- P38398/rs56046357 Breast cancer type 1 susceptibility protein 1646 F461L Breast cancer (BC) [MIM:114480] 3^ #103- P38398/rs56128296 Breast cancer type 1 susceptibility protein 1646 I379M - 2^ #103- P38398/rs56158747 Breast cancer type 1 susceptibility protein 1646 T1561I - 2^ #103- P38398/rs751656678 Breast cancer type 1 susceptibility protein 1646 H835Y Breast-ovarian cancer; familial; 1 (BROVCA1) [MIM:604370] 2^ #103- P38398/rs799917 Breast cancer type 1 susceptibility protein 1646 P871L - 2^ #103- P38398/rs80356876 Breast cancer type 1 susceptibility protein 1646 E1219D - 2^ #103- P38398/rs80357217 Breast cancer type 1 susceptibility protein 1646 E1282V Breast cancer (BC) [MIM:114480] 2^ #103- P38398/rs80357325 Breast cancer type 1 susceptibility protein 1646 R170W Breast cancer (BC) [MIM:114480] 3 #103- P38398/rs80357413 Breast cancer type 1 susceptibility protein 1646 N132K Breast cancer (BC) [MIM:114480] 2^ #103- P38398/rs80357480 Breast cancer type 1 susceptibility protein 1646 H888Y Breast cancer (BC) [MIM:114480] 2^ #103- P38398/rs876660005 Breast cancer type 1 susceptibility protein 1646 P798L Breast cancer (BC) [MIM:114480] 4 P38936/rs1801270 Cyclin-dependent kinase inhibitor 1 #1-164 S31R - 3 P38936/rs1801270 Cyclin-dependent kinase inhibitor 1 #1-94 S31R - 3 P38936/rs1801270 Cyclin-dependent kinase inhibitor 1 #9-84 S31R - 3 P38936/rs4986867 Cyclin-dependent kinase inhibitor 1 #1-164 F63L - 4
72 #OR UniProt/dbSNP Protein DR Mutation Disease/Phenotype predictors P38936/rs4986867 Cyclin-dependent kinase inhibitor 1 #1-94 F63L - 4 P38936/rs4986867 Cyclin-dependent kinase inhibitor 1 #9-84 F63L - 4 P46527/rs777354267 Cyclin-dependent kinase inhibitor 1B #1-198 P69L - 3^ P46527/rs777354267 Cyclin-dependent kinase inhibitor 1B #25-90 P69L - 3^ P49918/rs483352966 Cyclin-dependent kinase inhibitor 1C #1-316 M12L Beckwith-Wiedemann syndrome (BWS) [MIM:130650] 2^ P49918/rs483352970 Cyclin-dependent kinase inhibitor 1C #1-316 P70L Beckwith-Wiedemann syndrome (BWS) [MIM:130650] 3^ P49918/rs483352970 Cyclin-dependent kinase inhibitor 1C #27-97 P70L Beckwith-Wiedemann syndrome (BWS) [MIM:130650] 3^ P50616/rs3316 Protein Tob1 #147-345 K319R - 4 P51608/rs61751450 Methyl-CpG-binding protein 2 #261-330 P322L Rett syndrome (RTT) [MIM:312750] 3 P51671/- Eotaxin #1-31 L7P - 3^ Signal transducer and activator of P52630/rs2229363 transcription 2 #817-838 Q826H - 2^ Q02548/- Paired box protein Pax-5 #76-92 P80R - 3^ Q02548/rs868494257 Paired box protein Pax-5 #1-30 G24R - 2^ Q06787/rs121434622 Synaptic functional regulator FMR1 #281-422 I304N Fragile X syndrome (FRAX) [MIM:300624] 2^ G/T mismatch-specific thymine DNA Q13569/rs2888805 glycosylase #340-410 V367M - 3 G/T mismatch-specific thymine DNA Q13569/rs2888805 glycosylase #340-410 V367L - 3 Q16665/rs1802821 Hypoxia-inducible factor 1-alpha #776-826 T796A - 3^ MHC class I polypeptide-related sequence Q29983/rs1051792 A #152-161 M152V - 3 Transcriptional and immune response Q9NR00/rs6474226 regulator #1-106 V10I - 3^ Q9UM07/rs12733102 Protein-arginine deiminase type-4 #129-135 R131T - 3
aMutations were located by mapping the protein sequences extracted from the UniProt database to the DisProt database [5], which contains experimentally verified disordered regions. For those proteins with multiple verified disordered regions around the mutation, the longest
73 disordered region was documented in this table. We considered the prediction result to be ‘ordered’ if the score from DynaMine is equal or larger than 0.8. bDR = Disordered region cMutations in same format as Table S2. dNumber of predictors that agree that the mutations are located in ordered region. ^The predicted score of DynaMine for the mutation is between 0.69 and 0.8, which means the prediction is context dependent. Therefore, this prediction result was not taken into consideration.
74 Table S12. Protein context information (Pfam domaina [3], superfamily domainb [6], post-translational modification and mutation) for protein entries in Table S11
Superfamily Modified Disordered region Pfam domain Mutation domain residue
UniProt/dbSNP Protein DR Mutation Context Information
O15273/- Telethonin #91-167 E132Q
O15273/rs773317399 Telethonin #91-167 T137I
P00736/- Complement C1r subcomponent #193-305 D290G
P00736/- Complement C1r subcomponent #193-305 G297D
P00736/- Complement C1r subcomponent #193-305 L300P
P00736/- Complement C1r subcomponent #193-305 R301P
P00736/- Complement C1r subcomponent #193-305 Y302C
75 UniProt/dbSNP Protein DR Mutation Context Information
P00736/rs3813728 Complement C1r subcomponent #193-305 G261R
P01106/rs121918685 Myc proto-oncogene protein #1-88 P59A
P01106/rs121918685 Myc proto-oncogene protein #1-167 P59A
P01106/rs121918685 Myc proto-oncogene protein #1-143 P59A
P01106/rs28933407 Myc proto-oncogene protein #1-88 P57S
P01106/rs28933407 Myc proto-oncogene protein #1-167 P57S
P01106/rs28933407 Myc proto-oncogene protein #1-143 P57S
P01106/rs4645959 Myc proto-oncogene protein #1-88 N11S
P01106/rs4645959 Myc proto-oncogene protein #1-167 N11S
76 UniProt/dbSNP Protein DR Mutation Context Information
P01106/rs4645959 Myc proto-oncogene protein #1-143 N11S
P01112/rs121913233 GTPase HRas #58-66 Q61L
P01112/rs121913233 GTPase HRas #59-65 Q61L
P01112/rs121913233 GTPase HRas #59-67 Q61L
P01112/rs121917756 GTPase HRas #58-66 E63K
P01112/rs121917756 GTPase HRas #59-65 E63K
P01112/rs121917756 GTPase HRas #59-67 E63K
P01112/rs121917758 GTPase HRas #58-66 T58I
P01112/rs28933406 GTPase HRas #58-66 Q61K
77 UniProt/dbSNP Protein DR Mutation Context Information
P01112/rs28933406 GTPase HRas #59-65 Q61K
P01112/rs28933406 GTPase HRas #59-67 Q61K
Prelamin-A/C [Cleaved into: Lamin- P02545/- #386-664 K515E A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs11575937 #386-664 R482L A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs11575937 #386-664 R482Q A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs142000963 #386-664 R644C A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs201583907 #386-664 G523R A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs267607607 #386-664 T488P A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs267607642 #386-664 D461Y A/C
78 UniProt/dbSNP Protein DR Mutation Context Information
Prelamin-A/C [Cleaved into: Lamin- P02545/rs28928902 #386-664 R471C A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs56673169 #386-664 K542N A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs56984562 #386-664 R541C A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs56984562 #386-664 R541S A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57318642 #386-664 R527C A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57520892 #386-664 R527P A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57520892 #386-664 R527H A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57629361 #386-664 T528K A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57629361 #386-664 T528R A/C
79 UniProt/dbSNP Protein DR Mutation Context Information
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57830985 #386-664 R582H A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs57920071 #386-664 R482W A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs58362413 #386-664 W520S A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs58541611 #386-664 D446V A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs58932704 #386-664 R453W A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs59981161 #386-664 K486N A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs60580541 #386-664 A529V A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs60934003 #386-664 L530P A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs60992550 #386-664 N456I A/C
80 UniProt/dbSNP Protein DR Mutation Context Information
Prelamin-A/C [Cleaved into: Lamin- P02545/rs61224243 #386-664 E578V A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs61444459 #386-664 R541H A/C
Prelamin-A/C [Cleaved into: Lamin- P02545/rs61444459 #386-664 R541P A/C
P02788/rs1126478 Lactotransferrin #38-59 K47R
P03372/rs139960913 Estrogen receptor #1-184 H6Y
P04150/- Glucocorticoid receptor #77-262 D233N
P04150/rs542110718 Glucocorticoid receptor #77-262 L112F
P04156/rs16990018 Major prion protein #167-171 N171S
P04156/rs74315402 Major prion protein #23-124 A117V
81 UniProt/dbSNP Protein DR Mutation Context Information
T-cell surface glycoprotein CD3 delta P04234/rs45510201 #127-171 Q147R chain
P05121/rs6090 Plasminogen activator inhibitor 1 #1-23 V17I
P05121/rs6092 Plasminogen activator inhibitor 1 #1-23 A15T
P07602/- Prosaposin #385-391 C388F
P07602/rs121918110 Prosaposin #346-353 L349P
P07602/rs121918110 Prosaposin #330-377 L349P
P10275/- Androgen receptor #654-670 I665N
P10275/- Androgen receptor #142-485 Q445R
P10275/- Androgen receptor #142-485 M268T
82 UniProt/dbSNP Protein DR Mutation Context Information
P10275/- Androgen receptor #142-485 P271S
P10275/- Androgen receptor #844-849 R847G
P10275/rs138454018 Androgen receptor #142-485 P342L
P10275/rs201934623 Androgen receptor #142-485 P392S
P10275/rs773996740 Androgen receptor #142-485 P392R
P10912/rs6180 Growth hormone receptor #270-620 I544L
P10912/rs6183 Growth hormone receptor #270-620 P495T
P11387/rs6029542 DNA topoisomerase 1 #175-214 G214S
Cystic fibrosis transmembrane P13569/rs1800103 #708-831 I807M conductance regulator
83 UniProt/dbSNP Protein DR Mutation Context Information
Cystic fibrosis transmembrane P13569/rs397508363 #708-831 R766M conductance regulator
Cystic fibrosis transmembrane P13569/rs397508378 #708-831 E822K conductance regulator
Cystic fibrosis transmembrane P13569/rs397508381 #708-831 E826K conductance regulator
Potassium voltage-gated channel P15382/rs1805128 #72-91 D85N subfamily E member 1
Potassium voltage-gated channel P15382/rs199473350 #24-45 S28L subfamily E member 1
Potassium voltage-gated channel P15382/rs199473360 #72-91 E83K subfamily E member 1
Potassium voltage-gated channel P15382/rs199473361 #72-91 W87R subfamily E member 1
Potassium voltage-gated channel P15382/rs74315445 #72-91 D76N subfamily E member 1
Potassium voltage-gated channel P15382/rs74315446 #72-91 S74L subfamily E member 1
84 UniProt/dbSNP Protein DR Mutation Context Information
Potassium voltage-gated channel P15382/rs77442996 #107-129 V109I subfamily E member 1
#1362- P25054/rs137854578 Adenomatous polyposis coli protein S1395C
1745
P30291/rs34412975 Wee1-like protein kinase #1-292 G210C
#1144- P32004/- Neural cell adhesion molecule L1 S1224L 1257
P35611/rs4962 Alpha-adducin #430-737 N510I
P35612/rs17855969 Beta-adducin #409-726 T439A
P35869/rs2066853 Aryl hydrocarbon receptor #545-713 R554K
P35869/rs4986826 Aryl hydrocarbon receptor #545-713 V570I
Peroxisome proliferator-activated P37231/rs1800571 #112-174 P113Q receptor gamma
85 UniProt/dbSNP Protein DR Mutation Context Information
Peroxisome proliferator-activated P37231/rs1805192 #9-111 P40A receptor gamma
P37840/rs104893875 Alpha-synuclein #1-140 E46K
P37840/rs104893875 Alpha-synuclein #1-113 E46K
P37840/rs104893875 Alpha-synuclein #42-92 E46K
P37840/rs104893875 Alpha-synuclein #1-102 E46K
Breast cancer type 1 susceptibility #103- P38398/- S1187I protein 1646
Breast cancer type 1 susceptibility #103- P38398/- S1217Y
protein 1646
Breast cancer type 1 susceptibility #103- P38398/- R866Q protein 1646
Breast cancer type 1 susceptibility #103- P38398/- F1226L
protein 1646
86 UniProt/dbSNP Protein DR Mutation Context Information
Breast cancer type 1 susceptibility #103- P38398/- S1297P protein 1646
Breast cancer type 1 susceptibility #103- P38398/- G778C
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs273900719 S1301R protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs28897673 Y105C
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs28897682 N810Y
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs28897687 N1236K protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs397509022 G960D
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs397509034 T1025I protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs41286300 R866C
protein 1646
87 UniProt/dbSNP Protein DR Mutation Context Information
Breast cancer type 1 susceptibility #103- P38398/rs4986847 I925L protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs4986848 F989S
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs55688530 S186Y protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs56046357 F461L
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs56128296 I379M
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs56158747 T1561I protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs751656678 H835Y
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs799917 P871L protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs80356876 E1219D
protein 1646
88 UniProt/dbSNP Protein DR Mutation Context Information
Breast cancer type 1 susceptibility #103- P38398/rs80357217 E1282V protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs80357325 R170W
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs80357413 N132K protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs80357480 H888Y
protein 1646
Breast cancer type 1 susceptibility #103- P38398/rs876660005 P798L
protein 1646
P38936/rs1801270 Cyclin-dependent kinase inhibitor 1 #1-164 S31R
P38936/rs1801270 Cyclin-dependent kinase inhibitor 1 #1-94 S31R
P38936/rs1801270 Cyclin-dependent kinase inhibitor 1 #9-84 S31R
P38936/rs4986867 Cyclin-dependent kinase inhibitor 1 #1-164 F63L
89 UniProt/dbSNP Protein DR Mutation Context Information
P38936/rs4986867 Cyclin-dependent kinase inhibitor 1 #1-94 F63L
P38936/rs4986867 Cyclin-dependent kinase inhibitor 1 #9-84 F63L
P46527/rs777354267 Cyclin-dependent kinase inhibitor 1B #1-198 P69L
P46527/rs777354267 Cyclin-dependent kinase inhibitor 1B #25-90 P69L
P49918/rs483352966 Cyclin-dependent kinase inhibitor 1C #1-316 M12L
P49918/rs483352970 Cyclin-dependent kinase inhibitor 1C #1-316 P70L
P49918/rs483352970 Cyclin-dependent kinase inhibitor 1C #27-97 P70L
P50616/rs3316 Protein Tob1 #147-345 K319R
P51608/rs61751450 Methyl-CpG-binding protein 2 #261-330 P322L
90 UniProt/dbSNP Protein DR Mutation Context Information
P51671/- Eotaxin #1-31 L7P
Signal transducer and activator of P52630/rs2229363 #817-838 Q826H transcription 2
Q02548/- Paired box protein Pax-5 #76-92 P80R
Q02548/rs868494257 Paired box protein Pax-5 #1-30 G24R
Q06787/rs121434622 Synaptic functional regulator FMR1 #281-422 I304N
G/T mismatch-specific thymine DNA Q13569/rs2888805 #340-410 V367M glycosylase
G/T mismatch-specific thymine DNA Q13569/rs2888805 #340-410 V367L glycosylase
Q16665/rs1802821 Hypoxia-inducible factor 1-alpha #776-826 T796A
MHC class I polypeptide-related Q29983/rs1051792 #152-161 M152V sequence A
91 UniProt/dbSNP Protein DR Mutation Context Information
Transcriptional and immune response Q9NR00/rs6474226 #1-106 V10I regulator
Q9UM07/rs12733102 Protein-arginine deiminase type-4 #129-135 R131T
a Superfamily 1.75 HMM library and genome assignments server http://supfam.org b EMBL-EBI Pfam 31.0 http://pfam.xfam.org c MyDomains Image Creator http://prosite.expasy.org/
92 Supplementary figures
Fig. S1. The overall workflow of bioinformatics investigations performed in this study.
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Fig. S2. Predicted disorder scores according to DynaMine for mutated proteins found within DisProt [5], a database providing experimentally verified disordered regions of proteins. (A) Breast cancer type 1 susceptibility protein (UniProt ID: P38398 / BRCA1_HUMAN; Associated disease: found in breast cancer); (B) Cystic fibrosis transmembrane conductance regulator (UniProt ID: P13569 / CFTR_HUMAN; Associated disease: Congenital bilateral absence of the vas deferens [MIM: 277180]); (C) G/T mismatch- specific thymine DNA glycosylase (UniProt ID: Q13569 / TDG_HUMAN; Polymorphism) and (D) Aryl hydrocarbon receptor (UniProt ID: P35869 / AHR_HUMAN; Polymorphism).
94 Reference
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