THE CARDS Headline SLC1 SLC2 SLC3 SLC4 SLC5 SLC6 SLC7 SLC8 SLC9 High-a nity glutamate and Hexose and sugar alcohol Heavy subunits of heteromeric Bicarbonate transporters Sodium-dependent glucose Sodium and chloride-dependent Cationic amino acid transporters Sodium / calcium exchangers Sodium / proton exchangers neutral amino acid transporters transporters amino acid transporters transporters neurotransmitter transporters / glycoprotein-associated 1A 2A 3A 4A 2C 6A 6B 7A 8A

hSLC7A5 hSLC1A5 SubtitlePDB: 6RVX hSLC2A3 PDB: 4ZW9 hSLC3A2 PDB: 6IRT hSLC4A1 PDB: 4YZF hSLC5A10 Swiss-Model: A0PJK1 hSLC6A4 PDB: 6DZZ + SLC3A2 PDB: 6IRT MjNCX PDB: 3V5U EcNhaA PDB: 4AU5 Involved in neurotransmission, Involved in glucose intake and Assist in the plasma membrane Regulation of cell volume, intracellu- Glucose uptake in the small intestine Promotes adipogenic di erentiation Amino acid , NO Control mitochondrial and calcium Regulate cellular and vesicular pH metabolism, development and amino glucose metabolism. localization of SLC7 transporters. lar pH, CO uptake by red blood cells and glucose metabolism. Regulate and nervous system phenotypes. synthesis, redox balance. Some form homeostasis. Involved in apoptosis and volume. Control cell prolifera- acid homeostasis. Involved in adaptive immunity. and phagocytosis. electrical activity and cell volume. Involved in neurotransmission. heterodimers with SLC3 members. and signaling pathways. tion, growth, adhesion and migration.

rate rate rate rate rate rate rate rate rate st st Sugars: Glucose, fructose, st st st st st st st b Amino acids: Glutamate, anionic b b b b Sugars: Glucose, fatty acids, b Amino acids: Neurotransmitters, b Amino acids: most essential amino b b Ions: Sodium, potassium, lithium,

u Author 1, Authoru 2,galact osAuthore, glucosamine, urate, Omega, Authoru No substrate Herbert, Authoru Ions: Bicarbonate and other ions u u u u Ions: Calcium and sodium u

S S S S S S S S neutral amino acids S myoinositol, xylose myo-inositol, biotin, iodide, choline basic and neutral amino acids acids protons

tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za Pl. membrane, za za za za za za m za Pl. membrane SLC9A[1 - 9] li m li m li m li m li m li m li m li li m Pl. membrane e e e e SLC4A[1 - 5] e e SLC6A[1 - 9] Pl. membrane e SLC7A[1 - 11] e e a a a a a Pl. membrane a a a Pl. membrane a

SLC1A[1 - 7] M

M M M M M M M M c c c c c c c c

c ER, Lysosome, SLC2A[1 - 14] Pl. membrane SLC3A[1 - 2] Pl. membrane SLC5A[1 - 12] Pl. membrane SLC8A[1 - 4] Endosomes SLC9B[1 - 2]

o o o o o o o o

Mitochondria [7 - 11] [11 - 20] o Lysosomes [13-14] L L L L L L L L Keyword7 1, KeywordL Golgi, Vesicles 2,14 Keyword 3, Keyword2 4, Keyword 5, Keyword10 Vesicles 12 19 13 Mitochondria 4 Lysosomes 13 SLC9C[1 - 2]

ld ease Neuro ld ease ld ease ld ease ld ease ld ease Neuro ld ease ld ease ld ease o is o is o is Renal o is Neuro o is Renal o is o is Neuro o is o is Neuro F D Cancer F D Neuro F D F D F D F D F D F D F D No clan MFS No clan APC Neuro APC Respiratory APC No clan Cardio Renal Metabolic Cancer APC Renal Cancer Renal CPA/AT Cancer Immune Cardio Cardio Cancer Renal Cardio Metabolic Metabolic Orphans 0% Orphans 0%14% Orphans 0% Orphans 0% Orphans 0% Orphans 10% Orphans 23% Orphans 0% Orphans 23% Electrogenic 71% Electrogenic 71.4%7% Electrogenic 0% Electrogenic 20% Electrogenic 67% Electrogenic 95% Electrogenic 0% Electrogenic 25% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 14530974, 23506861 PMID: 23506862 PMID: 23506863 PMID: 23506864 PMID: 23506865 PMID: 23506866 PMID: 23506863 PMID: 23506867 PMID: 23506868, 31507243

SLC10 SLC11 SLC12 SLC13 SLC14 SLC15 SLC16 SLC17 SLC18 Sodium-bile acid Proton-coupled metal ion Electroneutral cation-coupled Human sodium-sulfate / Urea transporters Proton-coupled oligopeptide Monocarboxylate transporters Phosphate and organic anion Vesicular neurotransmitter transporters chloride cotransporters carboxylate cotransporters cotransporters transporters transporters 9A 10A 4B 11A 7B 1D 9C 9D 13B ? NmSLC10A2 PDB: 3ZUX EcoDMT PDB: 5M87 hSLC12A4 PDB: 6KKR VcINDY PDB: 5ULD hSLC14A1 PDB: 6QD5 XcPOT PDB: 6EI3 hSLC16A7 PDB: 7BP3 hSLC17A9 Swiss-Model: Q9BYT1 Involved in cell viability, neuronal Transport of metal ions across Contribute to ion uxes across Regulate levels of citric acid cycle Associated with Kidd (Jk) blood Regulate homeostasis of neuropep- Regulate glycolysis, glucose Involved in neurotransmission, urate Transport neurotransmitters and growth, neurotransmission and cellular membranes. Involved in tissues. Regulate cell volume, Cl- intermediates. group, urea accumulation, NO tides and peptide absorption. homeostasis, insulin secretion, fatty metabolism, development and amino hormones from the cytoplasm into energy homeostasis. antimicrobial action in macrophages. concentration and blood pressure. modulation and cardiac conduction. Associated with antiviral activity. acid and lipid metabolism. acid homeostasis. secretory vesicles.

rate rate rate rate rate rate rate rate rate st st st st Mixed: Sulfate, citrate, succinate, st st st Mixed: Ketone bodies, aromatic st Mixed: Purines, drugs, monocar- st b Mixed: Bile acids and steroid b Metals: Iron, manganese, cobalt, b b b b Amino acids: Dipeptides and b b b Mixed: Acetylcholine, amine,

u u u Ions: Chloride, sodium, potassium u pyruvate, oxalacetate, selenium, u Ions: Urea and urea analogues u u amino acids, thyroid hormones, u boxylates, nitrate, phosphate, Glu, u

S S S S S S S S hormones cadmium, nickel, lead, vanadium chromium S oligopeptides pyruvate, lactate, creatine ATP, urate, sialic acid histamine, spermidine, spermine

tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za za za za za za Pl. membrane za za li m li m li m li m li m li m li m li Pl. membrane m li m e Endosomes e e e e e e e e a a a a a a Pl. membrane a a a

M M M M M M M M M c c c c c c c c

Pl. membrane SLC10A[1 - 7] c Lysosomes SLC11A[1 - 2] Pl. membrane SLC12A[1 - 9] Pl. membrane SLC13A[1 - 5] Pl. membrane SLC14A[1 - 2] SLC15A[1 - 5] ER SLC16A[1 - 14] Lysosomes SLC17A[1 - 9] Vesicles SLC18A[1 - 4]

o o o o o o o o o

L L L L L L L L L Lysosomes 7 Pl. membrane 2 9 5 2 5 Golgi 14 Vesicles 9 4

ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease o is o is o is Cancer o is o is o is o is o is o is F F F F Neuro F F F Metabolic F Neuro F CPA/AT D Infectious APC D Infectious APC D Development IT D Development No clan D Renal MFS D Immune MFS D Cancer MFS D Immune MFS D Neuro Cancer Immune Metabolic Metabolic Cardio Metabolic Neuro Orphans 57% Orphans 0% Orphans 22% Orphans 0% Orphans 0% Orphans 20% Orphans 36% Orphans 0% Orphans 0% Electrogenic 29% Electrogenic 100% Electrogenic 0% Electrogenic 100% Electrogenic 0% Electrogenic 80% Electrogenic 0% Electrogenic 11% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 23506869 PMID: 23506870, 17109629 PMID: 23506871 PMID: 23506872 PMID: 23506873, 24055006, 11502588 PMID: 23506874 PMID: 23506875 PMID: 23506876, 31083648 PMID: 23506877, 25355561, 30846702

SLC19 SLC20 SLC21 / SLCO SLC22 SLC23 SLC24 SLC25 SLC26 SLC27 / thiamine transporters Type III sodium-phosphate Organic anion transporters Organic cation / anion / Sodium-dependent ascorbic acid Sodium / (calcium-potassium) Mitochondrial carriers Multifunctional anion exchangers Fatty acid transporters cotransporters zwitterion transporters transporters exchangers 14A 7C 13A 13C 14B 7D 9B 4C 16A ? ? hSLC20A1 Uniprot: Q8WUM9 hMFSD10 PDB: 6S4M AnUapA PDB: 5I6C hSLC24A1 Uniprot: O60721 TtADP/ATP carrier PDB: 6GCI hSLC26A9 PDB: 7CH1 hSLC27A2 Swiss-Model: O14975 Involved in vitamin metabolism as Involved in the intestinal absorption Involved in bile acid / salt metabo- Involved in drug uptake and drug Involved in the absorption and Involved in skin / hair / eye pigmen- Play a role in glucose, lipid, amino Involved in cellular pH regulation and Involved in immune system activa- well as in drug uptake. of dietary phosphate. Regulates lism, drug uptake and clearance, interactions. Regulate endocytosis of distribution of ascorbic acid. tation, vision and olfaction. acid and urea metabolism. Involved in sperm maturation. tion, fatty acid uptake and function secretion of parathyroid hormone. toxin elimination and blood pressure. metal- complexes. ATP synthesis and translocation. in bile acid metabolism.

rate rate rate rate rate rate rate rate rate st st st st Mixed: Drugs, neurotransmitters, st st st Mixed: Amino acids, protons, di / tri st Ions: Formate, oxalate, sulphate, st b Vitamins: Folate and thiamine b b Mixed: Bile acids, drugs, prosta- b b b b b b Lipids: Fatty acids, linoleate, oleate,

u u Ions: Phosphate and sodium u u nucleosides, steroid hormones, u Vitamins: Ascorbic acid u Ions: Calcium, potassium, sodium u carboxylic ions, Co-A, carnitine, u bicarbonate, chloride, iodide, u

S S S S S S S S

S glandines, hormones niacin, ions, carnitine metals, nucleotides. glyoxylate palmitate, bodipy-FA SLCO[1A2, SLC22A[1 - 18] SLC25A[1 - 6] tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za za za Pl. membrane za za za za za li m li Pl. membrane m li m 2A1, 3A1, 4A1, li m [23 - 25], 31 li m li m li m [10 - 48] li m li Pl. membrane m e e e e e Pl. membrane e e Pl. membrane e e

a Pl. membrane a a Pl. membrane a a Pl. membrane a a Mitochondria a a SLC27A[1 - 6]

M M M M M M M M M c c c c c c c c

SLC19A[1 - 3] ER SLC20A[1 - 2] c 5A1, 6A1, 1B1, Vesicles MFSD10 SLC23A[1 - 3] SLC24A[1 - 5] [51 - 53] SLC26A[1 - 11] Golgi

o o o o o o o o

Golgi o Endosomes L L L L L L L L L ER Peroxisomes 3 Vesicles 2 12 1B3, 1B7, 2B1, Mitochondria 28 SV2[A - C] 3 5 53 MTCH[1 - 2] 11 Mitochondria 6 1C1, 4C1] SVOP, SVOPL UCP[1 - 3] ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease Cancer ld ease o is Immune o is Infectious o is Metabolic o is Renal o is o is o is Neuro o is o is F D F D Cardio F D F D F D None F D Rare F D F D Metabolic F D Rare MFS Neuro No clan MFS Cancer MFS Cancer APC No clan disorders No clan Metabolic APC No clan Cardio Neuro Immune Immune Cancer Rare disorders disorders Orphans 0% Orphans 0% Orphans 17% Orphans 46% Orphans 33% Orphans 0% Orphans 38% Orphans 9% Orphans 17% Electrogenic 33% Electrogenic 100% Electrogenic 0% Electrogenic 0% Electrogenic 66% Electrogenic 20% Electrogenic 26% Electrogenic 27% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 23506878 PMID: 23506879 PMID: 23506880 PMID: 23506881 PMID: 23506882 PMID: 23506883 PMID: 23266187 PMID: 23506885, 31681763 PMID: 23506886

SLC28 SLC29 SLC30 SLC31 SLC32 SLC33 SLC34 SLC35(A) SLC35(B) Sodium-coupled nucleoside Equilibrative nucleoside Zinc transporters Copper transporters Vesicular inhibitory amino acid Acetyl-CoA transporters Type II sodium-phosphate Nucleoside-sugar transporters Nucleoside-sugar transporters transporters transporters transporters cotransporters 17A 17B 10B 10C 6C 15A 8D 17C 12D ? hSLC28A3 PDB: 6KSW hSLC29A1 PDB: 6OB7 hSLC30A8 PDB: 6XPF SsSLC31A1 PDB: 6M97 ? hSLC34A1 Uniprot: Q06495 mCST PDB: 6OH2 mCST PDB: 6OH2 Important for nucleotide synthesis. Involved in drug resistance and Regulates cellular zinc homeostasis. Regulator of cellular copper Involved in neuronal development Involved in cell viability and neuron Maintain phosphate homeostasis. Required for virus infection. Involved Required for virus infection. Involved Involved in drug uptake / resistance chemosensitivity. Play a role in Involved in development, body homeostasis. Involved in drug and neurotransmitter transport. growth. in development, autophagy and cell in development, autophagy and cell and chemosensitivity. nucleotide and T-cell homeostasis. weight and glucose metabolism. uptake. proliferation. proliferation.

rate rate rate rate rate rate rate rate rate st Nucleotides/nucleosides: AZT, st st st st st st st Nucleotides/nucleosides: Purines, st b b Nucleotides/nucleosides: b : Zinc, lead, manganese b : Copper and cisplatin b b b b b

u nucleosides, 5'-DFUR, d4T, u u Metals u Metals u Amino acids: GABA, Glycine u Other: Acetyl-CoA u Ions: Phosphate and sodium u pyrimidines, nucleotide-sugars, u Orphan

S S S S S S S S gemcitabine, antiviral drugs nucleosides and monoamines S thiamine SLC35A[4, 5] C2, D3, E[1, 2A, tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za za Pl. membrane za za za za za SLC35A[1 - 3] za 2B, 3, 4] li m li Pl. membrane m li m li m li m li m li Pl. membrane m li Pl. membrane m li Pl. membrane m e e e Pl. membrane e e e SLC33A1 e e e

a a SLC29A[1 - 4] a SLC30A[1 - 10] a a Pl. membrane a a SLC34A[1 - 3] a B[1 - 4], C1 a F[1, 2, 4, 5, 6] M M M M M M M M M c c c c c c c c

Pl. membrane SLC28A[1 - 3] Lysosomes ER, Golgi c SLC31A[1 - 2] SLC32A1 ER, Golgi Golgi Golgi, ER, Golgi, ER,

o o o o o o o o

Vesicles MFSD3 o L L L L L L L L L Vesicles 3 Mitochondria 4 Vesicles 10 2 1 2 Vesicles 3 Vesicles 11 D[1 - 2], F3 Vesicles 21 G[1 - 6] TMEM241

ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease Neuro ld ease Neuro o is o is o is Neuro o is o is o is o is o is o is F F F F F F F F Metabolic F D D Neuro D D D D D D D Metabolic No clan None MFS No clan Metabolic No clan Neuro APC None MFS Neuro No clan Renal DMT Immune Immune Cancer Cancer DMT Cancer Cancer Rare Rare disorders disorders Orphans 0% Orphans 0% Orphans 0% Orphans 0% Orphans 0% Orphans 50% Orphans 0% Orphans 0% Orphans 100% Electrogenic 100% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 100% Electrogenic 0% Electrogenic 100% Electrogenic 0% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 23506887 PMID: 23506887 PMID: 23506888 PMID: 23506889 PMID: 23506890 PMID: 23506891 PMID: 23506879 PMID: 23506892 PMID: 23506892

SLC36 SLC37 SLC38 SLC39 SLC40 SLC41 SLC42 SLC43(A) SLC43(B) Proton-coupled amino acid Sugar-phosphate / phosphate Sodium-dependent neutral Metal ion transporters Basolateral iron transporter Divalent cation transporters Rhesus ammonium transporters Sodium-independent system-L- Sodium-independent system-L- transporters exchangers amino acid transporters like amino acid transporters like amino acid transporters 6D 2D 1C 10D 18A 18B 4D 1B 17D ? ? ? ? DrSLC38A9 PDB: 6C08 hSLC39A13 Swiss-Model: Q96H72 hSLC40A1 PDB: 6W4S TtMgtE PDB: 2YVX hRhCG PDB: 3HD6 Responsible for the absorption and Involved in gluconeogenesis and Involved in amino acid uptake and Control Zn and Mn homeostasis. Involved in the accumulation of iron Involved in magnesium homeostasis. Factor that partially determines Involved in the ux of branched- Involved in the purine salvage e ux of amino acids produced glycolysis processes. metabolism, signaling and neuro- Involved in immunity, development, from the diet and regulates iron blood type, involved in ammonium chain amino acids (BCAAs). pathway in mammals. during intra-lysosomal proteolysis. transmission. cell migration and insulin secretion. homeostasis. transport, metabolism and excretion.

trate trate trate trate trate trate trate trate trate s s Sugars: Glucose, Glucose-6- s s s s s s s Nucleotide/nucleoside: 6-mercap- b Amino acids: GABA, glycine, alanine, b b Amino acids: Cationic and neutral b Metals: Zinc, cadmium, iron, nickel, b Metals: Iron, manganese, divalent b Metals: Magnesium, sodium and b Ions: Ammonium, , b b

u u phosphate, alendronate, zoledro- u u u u u u Amino acids: BCAA, amino alcohols u topurine, 6-thioguanine, adenine,

S S S S S S S S hydroxyproline, tryptophan S amino acids manganese, selenium metal ions divalent metal ion methylamine, methylammonium nate guanine, hypoxanthine

tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za za za Pl. membrane za za za za za li Pl. membrane m li m li m li m li m li m li m li m li m e ER e Pl. membrane e e e Pl. membrane e e RhAG, RhBG, e e

a SLC36A[1 - 4] a SLC37A[1 - 4] a SLC38A[1 - 11] a SLC39A[1 - 14] a Pl. membrane SLC40A1 a SLC41A[1 - 3] a a SLC43A[1 - 2] a SLC43A3

M M M M M M M M M c c c c c c c c

Golgi c ER, Golgi, Pl. membrane Pl. membrane Pl. membrane

o o o o o o o o

Lysosomes o Lysosomes Mitochondria RhCG L L L L L L L L Lysosomes 4 4 11 Vesicles 14 1 3 L 3 2 1

ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease o is o is o is o is o is o is o is o is o is F F F F Cancer F F F F F APC D Renal MFS D Cancer APC D Neuro DMT D MFS D Rare No clan D Neuro No clan D Rare MFS D Cancer MFS D Cancer Metabolic Cancer Immune disorders Renal disorders Neuro

Orphans 25% Orphans 25% Orphans 36% Orphans 7% Orphans 0% Orphans 0% Orphans 0% Orphans 0% Orphans 0% Electrogenic 50% Electrogenic 75% Electrogenic 27% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 23506890, 21501141 PMID: 23506893, 29719821 PMID: 23506890, 24193407 PMID: 23506894, 28875161 PMID: 23506870, 32814342 PMID: 23506895 PMID: 23506896 PMID: 23268354 PMID: 30910793, 26455426, 26527604

SLC44 SLC45 SLC46 SLC47 SLC48 SLC49 SLC50 SLC51 SLC52 -like Proton / sugar cotransporters Folate transporters Multidrug and toxin extrusion Heme transporter FLVCR-related transporters Sugar e ux transporter Steroid-derived molecules Ribo avin transporters transporters (MATE) transporters 11B 2B 14C 13D 15D 15C 3B 16B 14D ? ? ? hSLC44A1 Uniprot: Q8WWI5 hSLC47A1 Swiss-Model: Q96FL8 hSLC48A1 Uniprot: Q6P1K1 OsSWEET PDB: 5CTG hSLC51A Uniprot: Q86UW1 hSLC52A1 Uniprot: Q9NWF4 Promote cell proliferation and cell Involved in sperm maturation. Plays an important role in folate Involved in the secretion of organic Important for erythropoiesis. Important for erythropoiesis and Discovered in plants. Human homolog Regulate bile salt movements in the Important for the internal absorp- di erentiation. Important for the transport and metabolism. Involved cations and drugs into urine. systemic iron homeostasis. remains an orphan. small intestine, bile duct and liver tion of the essential ribo avin / generation of lung surfactant. in immunity and drug uptake. and contribute to steroid transport. vitamin B2.

rate rate rate rate rate rate rate rate rate st st st st st st st st st b b b Vitamins: Folate, heme, methotrex- b Mixed: Drugs, purines, organic b b b b Lipids: Bile acids, steroids, b

u Mixed: Choline and thiamine u Sugars: Galactose, glucose, sucrose u u u Other: Heme u Other: Heme u Orphan u u Vitamins: Ribo avin

S S S S S S S S

ate cations S estrone-3-sulfate, taurocholate

tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za za za za za za za za li m li m li m li m li m li m li m li m li m Pl. membrane e Pl. membrane e Pl. membrane e Pl. membrane e ER e Pl. membrane e FLVCR[1 - 2] e ER e SLC51A e

a a SLC45A[1 - 4] a SLC46A[1 - 3] a SLC47A[1 - 2] a SLC48A1 a a a a

M M M M M M M M M c c c c c c c c

SLC44A[1 - 5] c Unknown SLC50A1 Pl. membrane SLC52A[1 - 3]

o o o o o o o o

Mitochondria Melanosomes Lysosomes Mitochondria Endosomes Lysosomes SLC49A[3 - 4] Pl. membrane SLC51B o L L L L L L L L 5 4 3 2 1 L 4 1 2 3

ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease o is o is o is o is o is o is o is o is o is F F Rare F F F F F F F No clan D Cancer MFS D MFS D Metabolic No clan D None No clan D MFS D Rare No clan D None No clan D Metabolic No clan D Neuro disorders None disorders Metabolic Cancer

Orphans 60% Orphans 50% Orphans 33% Orphans 0% Orphans 0% Orphans 25% Orphans 100% Orphans 0% Orphans 0% Electrogenic 0% Electrogenic 25% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 23506897 PMID: 23506898, 28689241 PMID: 23506878, 26631267 PMID: 23506899 PMID: 23506900 PMID: 23506900 PMID: 23506865, 22157085 PMID: 23506901 PMID: 23506902

SLC53 SLC54 SLC55 SLC56 SLC57 SLC58 SLC59 SLC60 SLC61 Phosphate carrier Mitochondrial pyruvate carriers Mitochondrial cation / proton Sidero exins NIPA-like magnesium MagT-like magnesium Sodium-dependent lysophos- Molybdate transporters exchangers transporters transporters phatidylcholine symporters 8B 15B 8C 11C 18C 18D 16C 3C 3D ? ? ? ? ? hMPC1 Uniprot: Q9Y5U8 hLETM1 Uniprot: O95202 hSFXN1 Uniprot: Q9H9B4 hMAGT1 PDB: 6S7T Regulates phosphate homeostasis. Involved in glycolysis and oxidative Involved in apoptosis, glucose Involved in one-carbon metabolism, Regulate magnesium metabolism. Play a role in development. Involved in brain uptake of fatty Functional role unknown in humans. Functional role unknown in humans. Involved in virus infection and phosphorylation. metabolism and ATP synthesis. heme synthesis, mitochondrial acids and sphingolipid transport. development. respiration and erythropoiesis.

rate rate rate rate rate rate rate rate rate st st st st st st st st st b b b b b b b Lipids: Docosahexaenoic acid, b b

u Ions: Phosphate u Other: Pyruvate u Ions: Calcium u Mixed: Neutral amino acids, iron u Metals: Magnesium u Metals: Magnesium u u Orphan u Orphan: Molybdate in yeast

S S S S S S S S S sphingolipids, sodium

tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers tion bers za za za za za za za za za li m li m li m LETM1 li m li m li m li m li m li m e e MPC1, MPC2, e e Pl. membrane e NIPA[1 - 2] Pl. membrane e MAGT1 e MFSD2A e e a a a a a a a a a

M M M M M M M M M c c c c c c c c

Unknown XPR1 c Mitochondria Mitochondria LETM2 Mitochondria SFXN[1 - 5] Pl. membrane Unknown MFSD4A Unknown MFSD5

o o o o o o o o

o MPC1L Endosomes NIPAL[1 - 4] ER TUSC3 MFSD2B L L L L L L L L

1 3 3 LETMD1 5 6 2 2 L 1 1

ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease o is o is o is o is o is o is Immune o is o is o is F F F Rare F F Neuro F F F F IT D Neuro No clan D Cancer No clan D No clan D Rare DMT D Rare No clan D Infectious MFS D Neuro MFS D Cancer MFS D None Metabolic disorders disorders Cancer disorders Cancer

Orphans 0% Orphans 0% Orphans 67% Orphans 40% Orphans 33% Orphans 0% Orphans 0% Orphans 100% Orphans 100% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 17% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 23791524, 25938945, 27230854 PMID: 30770798, 27852261 PMID: 23716663, 19797662, 18045496, 12879013 PMID: 30442778, 30570704, 31059822 PMID: 17166836, 31207912, 25347071, 29464350 PMID: 19717468, 31036665 PMID: 24828044, 29563527 PMID: 26872374, 31710713 PMID: 27272503

SLC62 SLC63 SLC64 SLC65 CLN3 MFSD# OCA2 TMEM104 UNC93 Pyrophosphate transporter Sphingosine-phosphate Golgi calcium / proton NPC-type cholesterol Batten disease protein Atypical SLCs of major facilitator P protein Transmembrane protein 104 Protein UNC-93 transporters exchanger transporters superfamily (MFS) type 5A 11D 5B 16D 12C 5D 5C 12A 12B ? ? hANKH Uniprot: Q9HCJ1 HnSpinster PDB: 6E8J hTMEM165 Uniprot: Q9HC07 hNPC1 PDB: 6W5R hCLN3 Uniprot: Q13286 SeMelB PDB: 4M64 ? Functional role unknown in humans. Involved in apoptosis, immune cell Involved in Golgi-driven glycosyla- Important for cholesterol uptake in Involved in autophagy, protein Involved in cell-proliferation and cell Involved in melanin production. Functional role unknown in humans. Mediates stability and tra cking of tra cking and immunity. tion. the gut. Required for Ebola and tra cking and cellular response to cycle. endosomal TLRs. Marburg virus entry. osmotic stress.

rate rate rate rate rate rate rate rate rate st st Mixed: SPNS2 transports st st st st st st st b b b b b b b b b

u Orphan u sphingosine 1-phosphate, the rest u Orphan u Lipids: Cholesterol, sitosterol u Orphan u Orphan u Orphan u Orphan u Orphan

S S S S S S S S are orphan S

tion bers tion bers tion bers tion Endosomes bers tion bers tion bers tion bers tion bers tion bers za za za za za za za za za li m li m li m li m li m li m MFSD[1, 4B, 6, li m li m li Endosomes m e Pl. membrane e e Lysosomes e Endosomes e Pl. membrane e Lysosomes e Pl. membrane e e UNC93A

a a SPNS[1 - 3] a a NPC1 a CLN3 a a OCA2 a TMEM104 a

M M M M M M M M M c c c c c c c c

Unknown ANKH Golgi TMEM165 c 6L, 8, 9, 11, 12, ER, Golgi

o o o o o o o o

o Mitochondria Golgi Lysosomes Lysosomes Melanosomes Mitochondria UNC93B1

L L L L L L L L 1 3 1 2 NPC1L1 1 11 1 L 1 Lysosomes 2 Pl. membrane 13A, 14A, 14B]

ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease ld ease o is o is o is o is o is o is o is o is o is F Metabolic F F F F F F F F No clan D MFS D Rare No clan D Rare No clan D Metabolic No clan D Neuro MFS D Neuro IT D Rare APC D Rare MFS D Infectious Rare disorders disorders Neuro Cancer disorders disorders disorders

Orphans 100% Orphans 67% Orphans 100% Orphans 0% Orphans 100% Orphans 100% Orphans 100% Orphans 100% Orphans 100% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% Electrogenic 0% 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 20 40 60 80 100 0 0 0 0 0 0 0 0 0 PMID: 11326272, 12297987, 12297989, 13130483 PMID: 12815463, 30655317, 30973865 PMID: 31351090, 27401145 PMID: 30710017 PMID: 31568712, 15471887, 22261744, 30050370 PMID: 18638446, 27981419, 20826447, 28878041 PMID: 25513726, 19116314 PMID: 27939446 PMID: 23426999, 25187660, 29768176

The RESOLUTE project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (www.imi.europa.eu) under grant agreement No 777372. https://re-solute.eu This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This poster re ects @RESOLUTE_IMI only the authors' views and neither IMI nor the European Union and EFPIA are responsible for any use that may be made of the information contained therein. [email protected]