Regular Article Tissue-Specific Mrna Expression Profiles of Human Solute Carrier Transporter Superfamilies

Home , ABCB8, Sialin, SLC12A7, SLC12A8, SLC12A9, SLC13A2

Drug Metab. Pharmacokinet. 23 (1): 22–44 (2008). Regular Article Tissue-specific mRNA Expression Profiles of Human Solute Carrier Transporter Superfamilies

Masuhiro NISHIMURA and Shinsaku NAITO* Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan

Full text of this paper is available at http://www.jstage.jst.go.jp/browse/dmpk

Summary: Pairs of forward and reverse primers and TaqMan probes specific to each of 173 human solute carrier (SLC) transporters were prepared. The mRNA expression level of each target transporter was ana- lyzed in total RNA from single and pooled specimens of various human tissues (adrenal gland, bladder, bone marrow, brain, colon, heart, kidney, liver, lung, mammary gland, ovary, pancreas, peripheral leukocytes, placenta, prostate, retina, salivary gland, skeletal muscle, small intestine, smooth muscle, spinal cord, spleen, stomach, testis, thymus, thyroid gland, trachea, and uterus) by real-time reverse transcription PCR using an Applied Biosystems 7500 Fast Real-Time PCR System. Individual differences in the mRNA expression of human SLC transporters in the liver were also evaluated. These newly determined expression profiles were used to study the gene expression in the 28 different human tissues listed above, and tissues with high transcrip- tional activity for human SLC transporters were identified. These results are expected to be valuable for research concerning the clinical diagnosis of disease.

Keywords: SLC transporter; mRNA expression; tissue distribution; quantification; human

SLC28As, SLC29As, SLC36As, and SLC38As.9) However, the Introduction tissue distribution of the mRNA expression of many other hu- Solute carrier (SLC) transporters transport a variety of sub- man SLC transporters such as SLC8As, SLC9As, SLC11As, strates, including amino acids, lipids, inorganic ions, peptides, SLC12As, SLC13As, SLC14As, SLC16As, SLC17As, SLC18As, saccharides, metals, drugs, toxic xenobiotics, chemical com- SLC19AS, SLC20As, SLC23As, SLC24As, SLC25As, SLC26As, pounds, and proteins.1–8) Assessment of the protein levels SLC27As, SLC30As, SLC31As, SLC32A1, SLC33A1, SLC34As, and/or transport capacity of each SLC transporter is important SLC37As, SLC39As, SLC40A1, and SLC41As has not been in identifying the transporters that may be involved in the in- evaluated under the same experimental conditions. These im- flux and efflux of many substrates. However, such assessment portant transporters transport a variety of substrates such as of these SLC transporters in the same sample is difficult be- monocarboxylate, folate/thiamine, inorganic ions, metals, ami- causealargeamountofsampleisrequiredformeasurement. no acids, drugs, and other chemical compounds.4–8,10,11) For ex- Thus, we considered that rapid estimation should be possible ample, it is known that SLC16As are transporters for monocar- by the detailed evaluation of the mRNA expression levels of boxylate,4) SLC19As are transporters for folate/thiamine,5) each transporter in target tissues based on the findings of SLC11As, SLC30As, SLC39As, and SLC41As are transporters previous studies, followed by the evaluation of protein levels for metals,6,8) and SLC25As are transporters for a variety of and transport capacities. Investigation of the tissue-specific substrates such as ATP/ADP, amino acids, malate, ornithine, mRNA expression profiles of SLC transporters could therefore and citruline.10) The present study was therefore undertaken to provide important information concerning the mechanisms of investigate the mRNA expression levels of these 173 human the influx and efflux of endogenous and exogenous substrates. SLC transporters in total RNA from single and pooled speci- We have previously reported the tissue distribution of the mens of 28 adult human tissues using high-sensitivity real-time mRNA expression of large numbers of human SLC transport- reverse transcription PCR (RT-PCR). The nomenclature of the ers such as SLC1As, SLC2As, SLC3As, SLC4As, SLC5As, transporters that were evaluated in the present study is sum- SLC6As, SLC7As, SLC10As, SLC15As, SLC21As, SLC22As, marized in Table 1.

Received; August 20, 2007, Accepted; November 2, 2007 *To whom correspondence should be addressed: Shinsaku NAITO,Ph.D.,Division of Pharmacology, Drug Safety and Metabolism, Otsuka Phar- maceutical Factory, Inc., Naruto, Tokushima 772-8601, Japan. Tel. ＋81-88-685-1151, Fax. ＋81-88-686-8176, E-mail: naitousn＠otsukakj.co.jp

22 mRNA Expression Profiles of Human SLC Transporters 23

Table 1. Nomenclature of Target Genes Table 1. (continued)

Abbreviation Trivial Name(s)/Synonym(s) Abbreviation Trivial Name(s)/Synonym(s)

SLC8A1 NCX1, MGC119581, DKFZp779F0871 SLC24A4 NCKX4, SLC24A2, FLJ38852 SLC8A2 NCX2 SLC24A5 JSX, NCKX5 SLC8A3 NCX3 SLC24A6 NCLX, NCKX6, FLJ22233 SLC9A1 APNH, NHE1, FLJ42224 SLC25A1 CTP, SLC20A3 SLC9A2 NHE2 SLC25A2 ORC2, ORNT2, MGC119151, MGC119153 SLC9A3 NHE3, MGC126718, MGC126720 SLC25A3 PHC, OK/SW-cl.48 SLC9A4 NHE4, DKFZp313B031 SLC25A4 T1, ANT, ANT1, PEO2, PEO3 SLC9A5 NHE5 SLC25A5 T2, T3, 2F1, ANT2 SLC9A6 NHE6, KIAA0267 SLC25A6 ANT3, ANT3Y, MGC17525 SLC9A7 NHE7 SLC25A7 UCP1, UCP SLC9A8 NHE8, FLJ42500, KIAA0939, MGC138418, DKFZp686C03237 SLC25A8 UCP2, UCPH SLC9A9 NHE9, FLJ35613, Nbla00118 SLC25A9 UCP3 SLC9A10 SLC25A10 DIC SLC9A11 MGC43026, RP3-436N22.2 SLC25A11 OGC, SLC20A4 SLC11A1 LSH, NRAMP, NRAMP1 SLC25A12 ARALAR, ARALAR1 SLC11A2 DCT1, DMT1, NRAMP2, FLJ37416 SLC25A13 CTLN2, CITRIN, ARALAR2 SLC12A1 BSC1, NKCC2, MGC48843 SLC25A14 UCP5, BMCP1, MGC149543 SLC12A2 BSC, BSC2, NKCC1, MGC104233 SLC25A15 HHH, ORC1, ORNT1, D13S327 SLC12A3 TSC, NCCT SLC25A16 GDA, GDC, ML7, hML7, HGT.1, D10S105E, MGC39851 SLC12A4 KCC1, FLJ40489 SLC25A17 PMP34 SLC12A5 KCC2, KIAA1176 SLC25A18 GC2 SLC12A6 KCC3, ACCPN, KCC3A, KCC3B, DKFZP434D2135 SLC25A19 DNC, TPC, MUP1, MCPHA SLC12A7 KCC4, DKFZP434F076 SLC25A20 CAC, CACT SLC12A8 CCC9, FLJ23188, DKFZp686L18248 SLC25A21 ODC, ODC1, MGC126570 SLC12A9 CIP1, FLJ46905 SLC25A22 GC1, FLJ13044 SLC13A1 NAS1, NaSi-1 SLC25A23 APC2, MCSC2, MGC2615, SCaMC-3 SLC13A2 NADC1, NaDC-1 SLC25A24 APC1, SCAMC-1, DKFZp586G0123 SLC13A3 NADC3, SDCT2 SLC25A25 MCSC, PCSCL, SCAMC-2, KIAA1896, MGC105138, MGC119514, SLC13A4 SUT1, SUT-1 MGC119515, MGC119516, MGC119517, RP11-395P17.4 SLC13A5 NACT, MGC138356, DKFZp686E17257 SLC25A26 SAMC, DKFZp434E079 SLC14A1 JK, UT1, UTE, HUT11, RACH1, UT-B1, HsT1341, FLJ33745, FLJ41687 SLC25A27 UCP4, FLJ33552, RP11-446F17.2 SLC14A2 UT2, UTR, HUT2, UT-A2, hUT-A6, FLJ16167, MGC119566, MGC119567 SLC25A28 MRS4L, MRS3/4, NPD016, DKFZp547C109 SLC16A1 MCT, MCT1, FLJ36745, MGC44475 SLC25A29 CACL, C14orf69, FLJ38975 SLC16A2 AHDS, MCT7, MCT8, XPCT, DXS128, DXS128E SLC25A30 KMCP1 SLC16A3 MCT3, MCT4, MGC138472, MGC138474 SLC25A31 AAC4, ANT4, SFEC35kDa, DKFZp434N1235 SLC16A4 MCT4, MCT5 SLC25A32 MFT, MFTC, FLJ23872 SLC16A5 MCT5, MCT6 SLC25A33 MGC4399, BMSC-MCP SLC16A6 MCT6, MCT7 SLC25A34 RP11-169K16.2, DKFZp781A10161 SLC16A7 MCT2 SLC25A35 FLJ40217, MGC120446, MGC120448 SLC16A8 MCT3, REMP SLC25A36 FLJ10618 SLC16A9 MCT9, C10orf36, FLJ43803 SLC25A37 MSC, MFRN, MSCP, HT015, PRO1278, PRO1584, PRO2217 SLC16A10 TAT1, PRO0813 SLC25A38 FLJ20551, FLJ22703 SLC16A11 MCT11, FLJ90193 SLC25A39 CGI69, CGI-69, FLJ22407 SLC16A12 MCT12, DKFZp686E188 SLC25A40 MCFP SLC16A13 MCT13 SLC25A41 FLJ40442, MGC34725 SLC16A14 MCT14, FLJ30794 SLC25A42 MGC26694 SLC17A1 NPT1, NPT-1, NAPI-1, MGC126794, MGC126796 SLC25A43 SLC17A2 NPT3, MGC138238 SLC25A44 FLJ90431, KIAA0446, RP11-54H19.3 SLC17A3 HPRD:HPRD_10233 SLC25A45 SLC17A4 KAIA2138, KIAA2138, MGC129623 SLC25A46 SLC17A5 SD, AST, NSD, SLD, ISSD, SIASD, SIALIN, FLJ22227, FLJ23268 SLC26A1 EDM4, SAT1, SAT-1 SLC17A6 DNPI, VGLUT2 SLC26A2 DTD, EDM4, DTDST, MST153, D5S1708, MSTP157 SLC17A7 BNPI, VGLUT1 SLC26A3 CLD, DRA SLC17A8 VGLUT3 SLC26A4 PDS, DFNB4 SLC18A1 CGAT, VAT1, VMAT1 SLC26A5 PRES, DFNB61, MGC118886, MGC118887, MGC118888, MGC118889 SLC18A2 SVAT, SVMT, VAT2, VMAT2, MGC26538, MGC120477, MGC120478 SLC26A6 DKFZp586E1422 SLC18A3 VACHT, MGC12716 SLC26A7 SUT2, MGC126268 SLC19A1 CHMD, FOLT, IFC1, REFC, RFC1 SLC26A8 TAT1, FLJ32714 SLC19A2 TC1, THT1, TRMA, THTR1 SLC26A9 SLC19A3 SLC26A10 SLC20A1 PIT1, GLVR1, PiT-1, Glvr-1, FLJ41426, DKFZp686J2397 SLC26A11 MGC46523 SLC20A2 GLVR2,MLVAR,PIT-2,Glvr-2 SLC27A1 FATP, FATP1, ACSVL5, FLJ00336, MGC71751 SLC23A1 SVCT1, YSPL3, SLC23A2, MGC22361 SLC27A2 VLCS, FATP2, VLACS, ACSVL1, FACVL1, hFACVL1, HsT17226 SLC23A2 NBTL1, SVCT2, YSPL2, SLC23A1, KIAA0238 SLC27A3 FATP3, ACSVL3, VLCS-3, MGC4365 SLC23A3 E2BP3, SVCT3, Yspl1, FLJ31168 SLC27A4 FATP4, ACSVL4 SLC24A1 NCKX, RODX, NCKX1, HsT17412, KIAA0702 SLC27A5 ACSB, FATP5, ACSVL6, FACVL3, VLACSR, VLCSH2, VLCS-H2, FLJ22987 SLC24A2 NCKX2 SLC27A6 FATP6, ACSVL2, FACVL2, VLCS-H1, DKFZp779M0564 SLC24A3 NCKX3 SLC30A1 ZNT1, ZRC1 24 Masuhiro NISHIMURA and Shinsaku NAITO

Table 1. (continued) Table 2. Total RNA Source Information for Various Tissues

Abbreviation Trivial Name(s)/Synonym(s) Tissue Pool size Age Sex Race

SLC30A2 ZNT2, ZnT-2, PP12488, FLJ36708, MGC11303 Total RNA source (purchased from CLONTECH Laboratories, Inc.) SLC30A3 ZNT3 Adrenal gland 62 15–61 years female, male Caucasian SLC30A4 ZNT4 Bladder 20 17–60 years female, male Caucasian SLC30A5 ZNT5, ZTL1, ZNTL1, ZnT-5, MGC5499, FLJ12496, FLJ12756 SLC30A6 ZNT6, FLJ31101, MGC45055 Bone marrow 10 35–60 years female, male Caucasian SLC30A7 ZNT7, ZnT-7, ZnTL2, DKFZp686M0368 Brain 2 47, 55 years male Caucasian SLC30A8 ZnT-8 Colon 1 23 years female Caucasian SLC30A9 HUEL,ZNT9,GAC63,C4orf1 Heart* 10 21–51 years female, male Caucasian SLC30A10 ZnT-10, DKFZp547M236 Kidney* 14 18–59 years female, male Caucasian SLC31A1 CTR1, COPT1, hCTR1, MGC75487 Liver* 1 51 years male Caucasian SLC31A2 CTR2, COPT2, hCTR2 Lung 3 32–61 years female, male Caucasian SLC32A1 VGAT, VIAAT Mammary gland 1 27 years female Caucasian SLC33A1 AT1, AT-1, ACATN Ovary 15 20–60 years female Caucasian SLC34A1 NPT2, SLC11, NAPI-3, NPTIIa, SLC17A2 SLC34A2 NPTIIb, NAPI-3B, FLJ90534, NAPI-IIb Pancreas 1 35 years male Caucasian SLC34A3 HHRH, NPTIIc, FLJ38680 Peripheral leukocytes 14 19–52 years female, male Caucasian SLC37A1 G3PP, FLJ22340 Placenta 4 21–39 years female Caucasian SLC37A2 pp11662, FLJ00171, MGC71430 Prostate* 32 21–50 years male Caucasian SLC37A3 MGC32939 Retina 29 20–60 years female, male Caucasian SLC37A4 G6PT1, G6PT2, G6PT3, GSD1b, GSD1c, GSD1d, TRG19, PRO0685, MGC15729 Salivary gland* 24 15–60 years female, male Caucasian SLC39A1 ZIP1, ZIRTL Skeletal muscle* 7 20–68 years female, male Caucasian SLC39A2 ZIP2, MGC119190 Small intestine* 5 20–61 years female, male Caucasian SLC39A3 ZIP3 Smooth muscle 12 20–68 years male Caucasian SLC39A4 AEZ, ZIP4, FLJ20327, MGC74741 SLC39A5 ZIP5, LZT-Hs7, MGC34778 Spinal cord 22 20–69 years female, male Caucasian SLC39A6 LIV-1 Spleen 1 44 years female Caucasian SLC39A7 KE4, HKE4, ZIP7, RING5, H2-KE4, D6S115E, D6S2244E Stomach* 1 50 years male Caucasian SLC39A8 BIGM103, LZT-Hs6 Testis* 39 14–64 years male Caucasian SLC39A9 FLJ11274, MGC74989 Thymus* 3 20–38 years male Caucasian SLC39A10 LZT-Hs2, MGC126565, MGC138428, DKFZp781L10106 Thyroid gland* 65 15–61 years female, male Caucasian SLC39A11 C17orf26 Trachea* – 18–54 years female, male Caucasian SLC39A12 FLJ30499, MGC43205, MGC51099, bA570F3.1 Uterus* 3 40–61 years female Caucasian SLC39A13 FLJ25785 Total RNA source (obtained from HAB) SLC39A14 ZIP14, cig19, LZT-Hs4, KIAA0062 * SLC40A1 FPN1, HFE4, MTP1, IREG1, MST079, MSTP079, SLC11A3 Liver 1 33 years male Caucasian SLC41A1 MgtE Liver* 1 47 years female Caucasian SLC41A2 MGC125330, MGC125331, SLC41A1-L1, DKFZP434K0427 Liver* 1 49 years male Hispanic SLC41A3 FLJ20473, SLC41A1-L2 Liver* 1 32 years female Hispanic Liver* 1 51 years female Caucasian Liver* 1 33 years female Hispanic Liver* 1 38 years male Caucasian Materials and Methods Liver* 1 41 years female Caucasian Liver* 1 38 years male Caucasian Materials: Total RNA prepared from single and pooled Liver* 1 56 years male Caucasian specimens of adult human tissues (adrenal gland, bladder, bone marrow,brain,colon,heart,kidney,liver,lung,mammary —, No data available. *, The total RNA was the same as that used for the measurement of mRNA expression levels in our previous studies9,14). gland, ovary, pancreas, peripheral leukocytes, placenta, prostate, retina, salivary gland, skeletal muscle, small intestine, smooth muscle, spinal cord, spleen, stomach, testis, thymus, The GenBank accession number and the position from the in- thyroid gland, trachea, and uterus) was purchased from CLON- itiation codon are also shown in Table 3.Eachprimerand/or TECHLaboratories,Inc.(Hilden,PaloAlto,CA,USA).The probe was homology searched by an NCBI BLAST search to en- total RNA source information for these human tissues is shown sure that it was specific for the target mRNA transcript. The in Table 2. Yeast tRNA was purchased from Life Technol- primers and TaqMan probes were synthesized by the Genosys ogies, Inc. (Rockville, MD, USA), and the TaqMan One-Step Division of SIGMA-ALDRICH JAPAN K.K. (Ishikari, Hok- RT-PCR Master mix reagents kit was purchased from Applied kaido, Japan). The TaqMan probes contained 6-carboxyfluores- Biosystems (Foster City, CA, USA). All other chemicals used in cein (FAM) at the 5? end and 6-carboxytetramethylrhodamine this study were of reagent grade. (TAMRA) at the 3? end,andweredesignedtohybridizetoa Oligonucleotides: The pairs of primers and the TaqMan sequence located between the PCR primers. probes for peptidylprolyl isomerase A (PPIA) used for RT-PCR TaqMan RT-PCR conditions: Total RNA samples ob- analysis employed sequences that have been reported previous- tained from adult human tissues were diluted to 10 mg/mL ly.12) The pairs of primers and the TaqMan probes for the target with RNase-free water containing 50 mg/mL yeast tRNA. Total mRNAs were designed based on the human mRNA sequence RNA at 30 ng per 20 mL of reaction mixture was used for (Table 3) using Primer Express software (Applied Biosystems). measurement of the target mRNA in each tissue. For the RT- mRNA Expression Profiles of Human SLC Transporters 25

Table 3. Primers and Probes Used for RT-PCR Analysis

mRNA (GenBank No.) Forward primer (Position) Reverse primer (Position) Probe (Position)

SLC8A1 (NM_021097) 5?-CCCTCCTGTTTCGATTACGTG-3? (2311–2331) 5?-ACGCCCAGCCATTCCAGTA-3? (2407–2389) 5?-ACTGTGTTCTGGAAGGTCCTGTTTGCCTTC-3? (2344–2373) SLC8A2 (NM_015063) 5?-CGGGCAGTGGTGTACTTTGT-3? (211–230) 5?-TGAAACGGTCGGCGATG-3? (280–264) 5?-CCATGGTCTACATGTTTCTGGGAGTGTCC-3? (233–261) SLC8A3 (NM_033262) 5?-CAACCACTATTCGGGTCTGGA-3? (368–388) 5?-ACCCATGACCACACACCTCAA-3? (478–458) 5?-AAACTGTCTCCAACCTGACCCTTATGGCC-3? (392–420) SLC9A1 (NM_003047) 5?-ACCTGTTCCTCACTGCCATCA-3? (1433–1453) 5?-CGCTTCGTCTCTTGCTTTTTC-3? (1547–1527) 5?-CACTGTCATCTTCTTCACCGTCTTTGTGC-3? (1455–1483) SLC9A2 (NM_003048) 5?-CAGGTCATTAATAGGTTCCGGA-3? (1240–1261) 5?-AAACAGATGGCACCTCGAAGT-3? (1328–1308) 5?-TCCCCTGACCTTTAAGGACCAGTTCATCATTG-3? (1266–1297) SLC9A3 (NM_004174) 5?-TCTTCCACAGGACCATGCG-3? (1955–1973) 5?-CCTTCTTGTTCTGGTTGAGCC-3? (2029–2009) 5?-AAGCGCCTGGAGTCCTTCAAGTCGA-3? (1975–1999) SLC9A4 (NM_001011552) 5?-TGACAGCAGTGATCCAGGATC-3? (2043–2063) 5?-TTGTGCCTCTTGCTTCTGAAG-3? (2124–2104) 5?-ACGTTCAGCGCATGCTCTCGGATA-3? 2074–2097) SLC9A5 (NM_004594) 5?-TTCACCTGTCTCGGAAAGTAACA-3? (191–213) 5?-AACAATTCCCCCTAGCACCA-3? (273–254) 5?-CCCTGAGAGCTGCCTGCTGATTTTGC-3? (222–247) SLC9A6 (NM_001042537) 5?-AAACCGGCCTGGCTATGAT-3? (302–320) 5?-GGAACATGAATGCCATACCGA-3? (368–348) 5?-TATGGTCTTTTGGTGGGCCTTGTGC-3? (322–346) SLC9A7 (NM_032591) 5?-AGAGTTGGTGTTGACCCCGAT-3? (1672–1692) 5?-CCGTCCCCTTGTAAGACTTGA-3? (1742–1722) 5?-AAGACCCACCACCCAACAACGACA-3? (1694–1717) SLC9A8 (NM_015266) 5?-TTCGCCTCATGGACATCGA-3? (1412–1430) 5?-CTCCACAGTGTTGCCCATCTT-3? (1506–1486) 5?-ACACCGCAGGAACAAGAAGGACGTCAA-3? (1443–1469) SLC9A9 (NM_173653) 5?-CACCAGGAAGCAAATAACTTGG-3? (1519–1540) 5?-GGTCAAAGCTATACCACATTCTGAA-3? (1600–1576) 5?-TAAAAACATGACGAAAGCAGAGAGTGCTCGG-3? (1542–1572) SLC9A10 (NM_183061) 5?-CCCTGTTTTGTCTCGAGTTGG-3? (1047–1067) 5?-GGCATCCCCTTCATTTCACT-3? (1127–1108) 5?-TCAGTTGGCGCTGGATATTCATAATGGTCT-3? (1076–1105) SLC9A11 (NM_178527) 5?-TGAGCAGGTTCAGGGAACTTC-3? (3219–3239) 5?-AAAGACCGTGTTGACTGAGGC-3? (3330–3310) 5?-TAAGCAAGCTGCTGATAATCCAAGCATCTGAGC-3? (3245–3277) SLC11A1 (NM_000578) 5?-CCATTGTGGGCTCCGACAT-3? (431–449) 5?-AGGTGTCCACGATGGTGATGA-3? (544–524) 5?-CAGGAAGTCATCGGCACGGCCATT-3? (451–474) SLC11A2 (NM_000617) 5?-TTACTGGGCTGCATCTTGCTG-3? (383–403) 5?-TTGCATGTCTGAGCCGATGAT-3? (489–469) 5?-TATGTCACCGTCAGTATCCCAAGGTCCCAC-3? (407–436) SLC12A1 (NM_000338) 5?-TGAGAACCATGAGAGCAGTGC-3? (81–101) 5?-GAGCTTCATCCCCAAAAGAGG-3? 163–143) 5?-CTGCAGATGACAATACTGACCCACCACATT-3? (104–133) SLC12A2 (NM_001046) 5?-GGGCACCACCAGCACTACTAT-3? (580–600) 5?-CAGCGTCCATGGTGTTGTG-3? (661–643) 5?-ATGATACCCACACCAACACCTACTACCTGCG-3? (602–632) SLC12A3 (NM_000339) 5?-GCAAATGCAAGATCCGTGTG-3? (2597–2616) 5?-TGATCGCCTTTCTCTCCTGGT-3? (2665–2645) 5?-TCGTAGGCGGCCAGATTAACAGGATG-3? (2618–2643) SLC12A4 (NM_005072) 5?-GGTGCTCATGACACGTCGAAT-3? (715–735) 5?-TGTTCACATACTTGACCCCCA-3? (823–803) 5?-CCACTTTGAACAATATGCGTGTGTATGGGAC-3? (737–767) SLC12A5 (NM_020708) 5?-TCACAGATGAGTCACGAGGCTC-3? (2798–2819) 5?-ACTGTCACCAGCCGTCTCTTCT-3? (2889–2868) 5?-CCGGAGAAAGAATCCAGCCAACACG-3? (2823–2847) SLC12A6 (NM_133647) 5?-TCCTCGCCTCCTCACCTTT-3? (2319–2337) 5?-CACGATGACAGAGCCCACAAT-3? (2391–2371) 5?-CCTCACAGCTCAAAGCAGGAAAAGGTCTCAC-3? (2339–2369) SLC12A7 (NM_006598) 5?-TCCAGATGAAGAAGGACCTGC-3? (2666–2686) 5?-CGTTTTCAACCATCTCCACCA-3? (2749–2729) 5?-ATGTTCTTGTATCACTTGCGCATCAGCG-3? (2689–2716) SLC12A8 (NM_024628) 5?-CAAACAAAACACCCGTGGC-3? (1067–1085) 5?-CGTTCACTTGACCCACAAAAAC-3? (1144–1123) 5?-ATCTGCCTGACCAGCTTGGTGACCAT-3? (1090–1115) SLC12A9 (NM_020246) 5?-GCATGAAGCCCAACACGTT-3? (1862–1880) 5?-TCCGTCAGGAAATGGTCCT-3? (1931–1913) 5?-TCCTAGGTTTCTACGATGACGCTCCACC-3? (1883–1910) SLC13A1 (NM_022444) 5?-GTTCCTGGTTGGTCTGCACTT-3? (1105–1125) 5?-CTGGGATAAGAAAGAATAGCAGCC-3? (1201–1178) 5?-CAGAGTACCCTGGTTTTGCTACAGATTCAACTG-3? (1130–1162) SLC13A2 (NM_003984) 5?-ACTGCGTCATCCAGACCGA-3? (935–953) 5?-GACGAATAGGATGCTGATGGC-3? (1011–991) 5?-CTGGGCCCCATGACCTTTGCAGAA-3? (964–987) SLC13A3 (NM_022829) 5?-TGCCCTCCAACAAGGTCTG-3? (227–245) 5?-AGGATCTTGAGGGCGATTCG-3? (350–331) 5?-CCCCAGTACTTCCTCGACACCAACTTCC-3? (247–274) SLC13A4 (NM_012450) 5?-GCTGCACATTAACCCCCTCTA-3? (1614–1634) 5?-ACAGGCAGCATCACTGCAA-3? (1685–1667) 5?-CTGATCCCAGTCACCATGTGCATCTCC-3? (1639–1665) SLC13A5 (NM_177550) 5?-GCTGCCACTCGTCATTCTGAT-3? (72–92) 5?-GTGCACCAGTAAATGGCCAT-3? (152–133) 5?-CCAAGTTTGTCAGGTGTGCCTACGTCA-3? (98–124) SLC14A1 (NM_015865) 5?-AAAACCAGGTTTCGCCATGT-3? (56–75) 5?-GCTGGTTGGCAAGTTCTTTCA-3? (145–125) 5?-AAGGGAGAAGGTGCTTCCCCAAAGCT-3? (77–102) SLC14A2 (NM_007163) 5?-TCCATGGGTACAACGGGAT-3? (542–560) 5?-TGAAGGTCACAGGAAACAGAAGC-3? (637–615) 5?-CTGGTGGGACTGCTGATGGCCGCGTTCTC-3? (562–590) SLC16A1 (NM_003051) 5?-CAGCCCTGTGTTCCTCTGTACT-3? (459–480) 5?-ATTGGTCGCATGAGGGCTC-3? (593–575) 5?-TGGCCCCCCTCAATCAGGTTTTCT-3? (482–505) SLC16A2 (NM_006517) 5?-GCGCTACTTCACCTACGGGA-3? (810–829) 5?-CAGACACCACACCATTGGC-3? (931–913) 5?-CTTTGGTTGTGGCTGTTCCTTCGCCTT-3? (834–860) SLC16A3 (NM_001042422) 5?-CAGTGTCTTCTTCAAGGAGCTCA-3? (126–148) 5?-GGATGGAGGAGATCCAGGCT-3? (199–180) 5?-ACAGGAGTTTGGGATCGGCTACAGCG-3? (150–175) SLC16A4 (NM_004696) 5?-GCTGGGCCACAAGTATTCCTT-3? (314–334) 5?-ACCACAGCAGCCACTTGGTAT-3? (404–384) 5?-TTGTGTGACTATGGGACTTCTACCCGGTTTG-3? (339–369) SLC16A5 (NM_004695) 5?-AGGCCAGCAACAGCGAG-3? (137–153) 5?-TGCCATGTGGAGCACAGC-3? (198–181) 5?-CCTCTTGGTTCCCCTCCATCCTCAC-3? (155–179) SLC16A6 (NM_004694) 5?-GCACTGCTCAGACCCATCTTT-3? (592–612) 5?-ACTGCGCTTCTTTCCGATTT-3? (670–651) 5?-TCAGAGGACCAGCGTCACCGAAAA-3? (614–637) SLC16A7 (NM_004731) 5?-AGTGTGGCCCAGTTCTTCTTG-3? (1145–1165) 5?-AGCCCCACAGGACATGTACAT-3? (1236–1216) 5?-CCCTCCTCTTGCAGGTAAATTGGTGGATT-3? (1167–1195) SLC16A8 (NM_013356) 5?-AAGTTCCTGATGGCGCTCG-3? (778–796) 5?-GTCCTTGGCGTAGTTCACCA-3? (840–821) 5?-CTCTTCGTCCCCGCCATCCTG-3? (799–819) SLC16A9 (NM_194298) 5?-TCTTGACAAGAGCTACAGTAGTGAGG-3? (681–706) 5?-TGAAGTAGGCTGTCTTGTTTCCAG-3? (761–738) 5?-AATGCAGGATCACGTTAGCCAATGGTG-3? (710–736) SLC16A10 (NM_018593) 5?-TGCTCTTCGTGTCCATGCT-3? (278–296) 5?-AAGACGCTGACTATTGGGCAG-3? (404–384) 5?-AAACCTTCGGCTCCAAAGACGATGACA-3? (299–325) SLC16A11 (NM_153357) 5?-GCGTAGTCCCCTAGCTGCC-3? (681–699) 5?-GAGCCAAGTGCACGTAAGGAA-3? (799–779) 5?-TCGGCCTGAGTCTGTTCACACGC-3? (701–723) SLC16A12 (NM_213606) 5?-TGAGCTCATTTGCCACGAGTC-3? (302–322) 5?-ATGGCGATACCATAAGCAAGG-3? (449–429) 5?-CCTCACTCTGGGAGTTCTTACAGGTCTTGG-3? (336–365) SLC16A13 (NM_201566) 5?-ATGGCTGGGAGATGCAGTC-3? (810–828) 5?-CAGGGAACAGGGCTAGTGACA-3? (898–878) 5?-CAGGGCCTGTGACACGACTCCTGAT-3? (830–854) SLC16A14 (NM_152527) 5?-CCACCCAAACATTGATGGC-3? (72–90) 5?-CCCATGATGAGGATGTGCAC-3? (146–127) 5?-ATGGGCTTGGATGATGGTGCTCTCC-3? (93–117) SLC17A1 (NM_005074) 5?-TGCCTGAACCTCACAATGGTA-3? (115–135) 5?-AGGAGCTTCTTTGTGGAGGTG-3? (194–174) 5?-ATGGTGAATAGCACAGATCCACATGGTTTGC-3? (139–169) SLC17A2 (NM_005835) 5?-GGCTGGCTCTTATCATGCACT-3? (56–76) 5?-TTGAAGGCATCTGCAACAGG-3? (203–184) 5?-CTCAAACTTCACCATGATAACGCAGCGTG-3? (78–106) SLC17A3 (NM_006632) 5?-GATGAGACACTGATCCCCAGG-3? (10–30) 5?-TGCAGAAATGTAAGACGAGGG-3? (88–68) 5?-AAGGTCCAAGTTTATGTTCTGCTCGCTATGG-3? (32–62) SLC17A4 (NM_005495) 5?-TCTGCCATCAGCAGCTTCTGT-3? (1207–1227) 5?-GCTCCAGCTATGTGTGCAAAG-3? (1322–1302) 5?-CAGGAGCCCTTGTTAACTTCTTGGATATTGC-3? (1232–1262) SLC17A5 (NM_012434) 5?-CGGGTAAGAAGTACCAATGGG-3? (290–310) 5?-CCTCCAGGAATCTGTGTGATG-3? (380–360) 5?-CAGAAACTCAAGGATGGATTCTCGGTTCC-3? (314–342) SLC17A6 (NM_020346) 5?-TAGAGAGGAGTAGACTGGCAACCAC-3? (626–650) 5?-GAATGCCAGCTAAAGGCATTG-3? (706–686) 5?-TTTGTGGTTCCTATGCCGGAGCTGTGA-3? (656–682) SLC17A7 (NM_020309) 5?-GCAGAAAGCCCAGTTCAGC-3? (312–330) 5?-TGACAATGTAGCCCCAGAAAA-3? (388–368) 5?-ATCCAGAGACTGTCGGCCTCATACACGG-3? (335–362) SLC17A8 (NM_139319) 5?-AAGGTGGGTCTCTTGTCAGCA-3? (1051–1071) 5?-AATCAGCCAATTGTCCTCCA-3? (1126–1107) 5?-TCCCACACATGGTTATGACAATCGTTGTACC-3? (1073–1103) SLC18A1 (NM_003053) 5?-TGGCACTACTGGATGGAGCA-3? (797–816) 5?-GAGTCCCCTTGGCACTCTCA-3? (874–855) 5?-CAGCTTTGCATCCTACAGCCTTCCAAAGTC-3? (820–849) SLC18A2 (NM_003054) 5?-CAGACAGCTTCCAGAGCATCTT-3? (215–236) 5?-AAGTGTCAGGTCTCTGGTAGCATT-3? (294–271) 5?-TCCTATTATGATAACTCGACTATGGTCACCGGG-3? (238–270) SLC18A3 (NM_003055) 5?-TACGGAGAGCGAAGACGTGAA-3? (348–368) 5?-GTAGCTCATGCGGTCGATGAA-3? (453–433) 5?-TGCTGTTTGCTTCCAAGGCTATCCTGC-3? (377–403) SLC19A1 (NM_194255) 5?-ACCTCGTGTGCTACCTTTGCT-3? (80–100) 5?-CCGCGTGAAGTTCTTGTCG-3? (183–165) 5?-CTACGGCTTCATGGCGCAGATACG-3? (102–125) SLC19A2 (NM_006996) 5?-TGGCATCAAGGTACAAAATGGT-3? (684–705) 5?-GACTCAATGTCCTCCCAGCC-3? (764–745) 5?-TTACTGACACCCCAGCTTCTAACCACCTTC-3? (713–742) SLC19A3 (NM_025243) 5?-CCTGGCGAACATGTCGTACT-3? (489–508) 5?-AAACATGCTTTTCTTGGGCA-3? (594–575) 5?-TTACCTCAACGTCATATCCTTGGCCTCTG-3? (510–538) SLC20A1 (NM_005415) 5?-TTGACTGGCGTCTCTTTCGTA-3? (1925–1945) 5?-ATGGCAGCACTGATAACTCCA-3? (2003–1983) 5?-ATTTTTATGGCCTGGTTTGTCACAGTCCCC-3? (1948–1977) SLC20A2 (NM_006749) 5?-TCCTGAGGCTTCCAATCTCAG-3? (320–340) 5?-TACCGATTGCGACCAGTGA-3? (394–376) 5?-ACGCACTGCATTGTGGGTTCTACTATAGGA-3? (343–372) SLC23A1 (NM_005847) 5?-TGGAGAGATGGAAATGCCC-3? (371–389) 5?-GCCAAATATGAGAGGTGTTCAGG-3? (448–426) 5?-CCGGAAGAGGAGATCTACGGTAACTGGA-3? (391–418) SLC23A2 (NM_005116) 5?-GTCGCCAGCATCATCGAGTC-3? (1162–1181) 5?-ATTCCCCTGTTTATTGCGTGG-3? (1256–1236) 5?-ATTGGTGACTACTACGCCTGTGCACGGC-3? (1183–1210) SLC23A3 (NM_144712) 5?-AGCTTCTACCTGGCTGACATAGACT-3? (973–997) 5?-ACCATCTTGGCAGCAGCAA-3? (1060–1042) 5?-TGGGCGAAATATCTTCATTGTGGGCTTC-3? (999–1026) SLC24A1 (NM_004727) 5?-TGTGTTTGTGGCCTTGGC-3? (1392–1409) 5?-CCTCGGAGATCTGCAGCTTG-3? (1477–1458) 5?-TTTGCGACGAGTACTTCGTTCCAGCC-3? (1415–1440) SLC24A2 (NM_020344) 5?-TGCCATCGTCCTTCTCTTCAT-3? (1815–1835) 5?-GCCCAGGATTTTGTTCATTCG-3? (1899–1879) 5?-TCTTCGTCATCCTCTCTATCGCCCTCTG-3? (1844–1871) SLC24A3 (NM_020689) 5?-GAACATGGTCAACGGATTGG-3? (819–838) 5?-CTTTGCGGTGGAAATTTGCT-3? (919–900) 5?-CTGAAATTGATGACAGCAGCAACTGCGA-3? (848–875) SLC24A4 (NM_153646) 5?-GGTCTATTCCGTGGTCCTGTT-3? (1623–1643) 5?-GTAGACACCCAGCTTCCGGT-3? (1719–1700) 5?-CTCTCACCGTCCTCGGCATCCACCTA-3? (1658–1683) 26 Masuhiro NISHIMURA and Shinsaku NAITO

Table 3. (continued)

mRNA (GenBank No.) Forward primer (Position) Reverse primer (Position) Probe (Position)

SLC24A5 (NM_205850) 5?-GCCTGTCTTGCCAAAGCTATG-3? (697–717) 5?-CGACGAATGAATGGTTGACC-3? (779–760) 5?-AAGTGAACAACAGCCACTGATGGGCTG-3? (723–749) SLC24A6 (NM_024959) 5?-GGTGTGTGGCCTGAATGTCTC-3? (165–185) 5?-CCCATCACTGTGGCAGTCA-3? (234–216) 5?-ACCGCTGTGACTTCATCCGGACCA-3? (188–211) SLC25A1 (NM_005984) 5?-ATGGAGACCATCAAGGTGAAGTTC-3? (427–450) 5?-AATCTCCCTAACCCCGTGGAA-3? (513–493) 5?-TCCACGACCAGACCTCCCCAAACC-3? (452–475) SLC25A2 (NM_031947) 5?-TTGGTCTGTCGTGAAGGGTATC-3? (459–480) 5?-CTGACGCAAAAAACGATCG-3? (601–583) 5?-AAAAGGATGGCCCCTTGGGCTTCTACC-3? (485–511) SLC25A3 (NM_005888) 5?-CACTTAAAGAGGATGGTGTTCGTG-3? (329–352) 5?-CTGCATGGAGTAGCCAAGGAA-3? (399–379) 5?-TTTGGCTAAAGGATGGGCTCCGAC-3? (354–377) SLC25A4 (NM_001151) 5?-CAACGTGATCCGTTACTTCCC-3? (228–248) 5?-GATCCACACCCCCTAAGAAGA-3? (313–293) 5?-ACCCAAGCTCTCAACTTCGCCTTCAA-3? (250–275) SLC25A5 (NM_001152) 5?-AAGGAGCAGGGAGTTCTGTCC-3? (187–207) 5?-GCGAAGTTAAGAGCCTGGGTG-3? (269–249) 5?-TCTGGCGCGGTAACCTGGCCAAT-3? (209–231) SLC25A6 (NM_001636) 5?-ATGATGATGCAGTTCGGGC-3? (712–730) 5?-ATCTTCCTCCAACAGTCGACG-3? (782–762) 5?-CAAAGGAGCTGACATCATGTACACGGGC-3? (732–759) SLC25A7 (NM_021833) 5?-GCCCGACGTCCAGTGTTATTA-3? (140–160) 5?-TAGAGTTTCATCCGCCCTTCT-3? (224–204) 5?-TATAAAGGTGTCCTGGGAACAATCACCGCTG-3? (163–193) SLC25A8 (NM_003355) 5?-TGTGCTGAGCTGGTGACCTAT-3? (571–591) 5?-CCCAAAGGCAGAAGTGAAGTG-3? (669–649) 5?-CCCTCCTGAAAGCCAACCTCATGACA-3? (608–633) SLC25A9 (NM_022803) 5?-TTTCAGGCCAGCATACACCTC-3? (430–450) 5?-GGGCAAAGTTCCTTTCCACA-3? (552–533) 5?-CCATCCAGGAGCGACAGAAAATACAGCG-3? (454–481) SLC25A10 (NM_012140) 5?-CCTCTCTGACAACATCTTCACTCA-3? (582–605) 5?-AGTGGAAAACGCCCTGATACTC-3? (718–697) 5?-TTTGTCGCCAGCTTTATTGCAGGTGG-3? (607–632) SLC25A11 (NM_003562) 5?-TCCAGAACATGCGGATGATT-3? (740–759) 5?-CGTAGCGGACAACTTTGAACA-3? (817–797) 5?-ATGGGAAGCCGGAATACAAGAACGGG-3? (761–786) SLC25A12 (NM_003705) 5?-CAGCTCGAGTGTTTCGATCCT-3? (1742–1762) 5?-AGGTGTTGGTTCTGAACCAGC-3? (1863–1843) 5?-TCCCCAGTTTGGTGTTACCTTGGTCAC-3? (1764–1790) SLC25A13 (NM_014251) 5?-TTGCTCCTCTGGAAGAGGGA-3? (878–897) 5?-GGCCGACTCTGCAACTTGT-3? (987–969) 5?-CTCTGCCCTTTAACTTGGCTGAGGCC-3? (899–924) SLC25A14 (NM_022810) 5?-TTGTATATGGCGGCCTTGC-3? (122–140) 5?-GAACCTGAAGTCGTGTTTTGGT-3? (202–181) 5?-TCTATCGTGGCTGAGTTTGGGACTTTCC-3? (142–169) SLC25A15 (NM_014252) 5?-AGCCAAGAGCCAGAATACAGTG-3? (438–459) 5?-CGAAGTAAAGTGCTTGAGAGTCCA-3? (536–513) 5?-ATCAAAAGTATTCTTAGGAAAGATGGCCCCTTGG-3? (469–502) SLC25A16 (NM_152707) 5?-GCAGGTATGACAGCAGTTATCTGTAC-3? (418–443) 5?-CTGTATAGCTGTGTTCCCCTTTCA-3? (508–485) 5?-CTCTTGACATGGTTAGGGTCCGCCTAGCAT-3? (449–478) SLC25A17 (NM_006358) 5?-TCCAAAACTACACACATGGTGC-3? (133–154) 5?-AGAGACTGGAAATCACTGGAAACC-3? (226–203) 5?-CATTAAAGAAGAAGGACTCCTGGCACCATATCG-3? (165–197) SLC25A18 (NM_031481) 5?-CCCACTGTTTGCCAACCTTA-3? (603–622) 5?-GCTATGGAACCTGCCACACA-3? (704–685) 5?-TTCAACGAGCTCGCCGGTAAGGC-3? (634–656) SLC25A19 (NM_021734) 5?-AGGGTTTGAGCATGCCAGA-3? (741–759) 5?-TGCTTGGCACAGTCCATGA-3? (812–794) 5?-CTGCCTTTGGCCAGGTACGGAGATACAA-3? (761–788) SLC25A20 (NM_000387) 5?-GCTATCCCCAGCTTTTTGCA-3? (326–345) 5?-AGCACTTGATCCGTTCTCCA-3? (409–390) 5?-CTGGGATGTTATCTGGCGTATTCACCACA-3? (347–375) SLC25A21 (NM_030631) 5?-TTGCAAGCAAATCGGAACAC-3? (409–428) 5?-CCCAGCCTTCCTTCTTAATGA-3? (490–470) 5?-TTTGCAGAGCAACCATCCACTGTGGG-3? (430–455) SLC25A22 (NM_024698) 5?-AACCCCTGTGATGTGGTGAAG-3? (730–750) 5?-CCTCGTGCCGCAGGATC-3? (838–822) 5?-CTCCAGTCACTTCAGCGAGGCGTCAA-3? (757–782) SLC25A23 (NM_024103) 5?-TCTGGGCATTTCCATCTCG-3? (324–342) 5?-TGGTCATTGTGCCGTCTCG-3? (397–379) 5?-CAGGCTGAGAAAATTTTGCACAGCATGG-3? (349–376) SLC25A24 (NM_013386) 5?-ATTTGGTGGCTTTCGACAGATG-3? (702–723) 5?-AGGAGCAATTTTGATGACGTTTG-3? (789–767) 5?-TAAAAGAAGGAGGTATCCGCTCGCTTTGGA-3? (725–754) SLC25A25 (NM_052901) 5?-TGGCATCAACGTCCTCAAA-3? (738–756) 5?-CAACAAGGCGCTTGATCTG-3? (814–796) 5?-TTGCCCCCGAATCAGCCATCAAA-3? (758–780) SLC25A26 (NM_173471) 5?-CATATGTTGGCTGCCTCTGCT-3? (271–291) 5?-GATACCTGTGCCCTCTGCTTAAC-3? (356–334) 5?-AAGTGGTTGCCTGCCTGATTCGAGTTC-3? (296–322) SLC25A27 (NM_004277) 5?-AGCAACCTTTCCCCTGGAT-3? (105–123) 5?-ACCGAGCAAGAGCTGCTTCT-3? (172–153) 5?-TCACAAAAACTCGACTCCAAATGCAAGG-3? (125–152) SLC25A28 (NM_031212) 5?-CAGGACATATCACAGGCATGG-3? (344–364) 5?-AAATTACTCTGGCCTGCACCC-3? (439–419) 5?-TAGTGCCTTCAGGACGGTATATCAAGTAGGTGG-3? (366–398) SLC25A29 (NM_001039355) 5?-CTTGTGGGACACCCGTTTG-3? (49–67) 5?-CGCTCTCTTGCTTGATGATGG-3? (163–143) 5?-CACGGTCAAGGTACGGCTTCAGGTC-3? (69–93) SLC25A30 (NM_001010875) 5?-TGTTACGCCAGGCATCCTATG-3? (227–247) 5?-GGGCGTTCAATGAATAGTCGC-3? (302–282) 5?-CACCATCAAGATAGGCACTTACCAGAGCTTG-3? (249–279) SLC25A31 (NM_031291) 5?-GAAAAACAGTTCTGGAGGTGGTTT-3? (352–375) 5?-GTTCGGGCAAAATCTAGAGGAT-3? (452–431) 5?-AAACCTGGCTTCTGGTGGAGCTGCTG-3? (381–406) SLC25A32 (NM_030780) 5?-GCCATGACCCTCTGCATTACA-3? (394–414) 5?-CATTCCTTTATATTGTCGGTGTGG-3? (498–475) 5?-CCCATTATGGGTAACAAAAACTCGCCTTATG-3? (417–447) SLC25A33 (NM_032315) 5?-TGTGCCTCCTGCATTGCTT-3? (736–754) 5?-TTGTACTTGGTGCCCTCTTCC-3? (806–786) 5?-TCCACACGAAGTCATAAGGACGAGGC-3? (756–781) SLC25A34 (NM_207348) 5?-TGGCTGCCGGCCTTC-3? (218–232) 5?-ACGGTGCCACCTGGTTG-3? (320–304) 5?-CAAGGCCTCATGAATGGCGTTCGTT-3? (238–262) SLC25A35 (NM_201520) 5?-TGCACAAGGCTCTACAACCAG-3? (688–708) 5?-GCTGAAGCACTGCATGATGTT-3? (773–753) 5?-ACAGATGCACAGGGCAAGAACCGA-3? (712–735) SLC25A36 (NM_018155) 5?-TGATTTCAGCTGCAATGGCA-3? (365–384) 5?-CTTGCATCAAGCTGTAACCGA-3? (452–432) 5?-TTTACTGCAATCACAGCAACCAACCCCA-3? (388–415) SLC25A37 (NM_016612) 5?-CGAATGCAGAGTTTGAGTCCA-3? (214–234) 5?-CCGCATGATTTTCTTGAGGG-3? (288–269) 5?-TCCCAAAGCCCAGTACACAAGTATCTACGGA-3? (237–267) SLC25A38 (NM_017875) 5?-CGCTTATGTTACATCCGGTGA-3? (62–82) 5?-TTGGAAAAGGAGGGTAGAGCA-3? (138–118) 5?-AAGGCTTTCCTGTGTGGCTCCATCAGT-3? (85–111) SLC25A39 (NM_016016) 5?-CTGTGCCACCTGGTTTCAAG-3? (255–274) 5?-GTGCCTCACGATCTTCACGA-3? (327–308) 5?-CTACCCGCTTCACTGGCACCATGGA-3? (278–302) SLC25A40 (NM_018843) 5?-GAACCAAGATGCAGTCCAAGAAG-3? (497–519) 5?-CCAAAGGGAAATCCAACCA-3? (588–570) 5?-TTCTTACGTGGAACTGCATCGATTTGTCAGC-3? (522–552) SLC25A41 (NM_173637) 5?-GCATCAACGTGCTCAAGATTG-3? (44–64) 5?-GGGACCCTTGTATTCCACAGA-3? (136–116) 5?-TCCTGAGTATGCCATCAAGTTCTCCGTATTCG-3? (66–97) SLC25A42 (NM_178526) 5?-TGCCAAAACAGCGGTAGCT-3? (138–156) 5?-GTGTAGTAGAGGACCCGGAAGG-3? (239–218) 5?-CCTGGACCGAACCAAAATCATCTTCCA-3? (159–185) SLC25A43 (NM_145305) 5?-GGCTCCTCCATGCTTTTTCTA-3? (437–457) 5?-GTCCGTTCCAGATTTTCTCCA-3? (583–563) 5?-TATTTACCAACAGGAAGGGTTCCTTGCCCTTT-3? (459–490) SLC25A44 (NM_014655) 5?-GGACAAACGCAACATCCAGAT-3? (6–26) 5?-ATTGCCACACCAAACACGTAG-3? (80–60) 5?-TCGAGTGGGAACACCTGGACAAGAAGA-3? (29–55) SLC25A45 (NM_182556) 5?-GGCTTTGCAGGCATTGCTT-3? (625–643) 5?-TACACTCTGCGTCTCAGTCCATC-3? (716–694) 5?-CAGCCACGCCCTTAGACATGATCAA-3? (653–677) SLC25A46 (NM_138773) 5?-GGAAGAGTGATAGGCATGGGA-3? (733–753) 5?-AAGCACCGTAGGGAAGATCAA-3? (810–790) 5?-CCTCATAGCAAACGACTTCTTCCGCTTCTTT-3? (757–787) SLC26A1 (NM_022042) 5?-CATCGCCTACTCATTGCTGG-3? (261–280) 5?-GAAGATGCCCACGGAGACA-3? (378–360) 5?-ACAGCCTCTATACGTCCTTCTTCGCCAAC-3? (299–327) SLC26A2 (NM_000112) 5?-TTGGGTACCTCCCGTCACA-3? (460–478) 5?-GGAGCACTATGGGCATTGTCA-3? (575–555) 5?-CTCTGTGGGCATTTTTGGAGTACTGTGCCTTAT-3? (480–512) SLC26A3 (NM_000111) 5?-TTGCTCTGCTGGTCGACATT-3? (281–300) 5?-AACGGACCCACGGATATGTGT-3? (389–369) 5?-CCCCAGTCTATGGGTTGTATGCATCCTTT-3? (302–330) SLC26A4 (NM_000441) 5?-AGGAATGGCTGCTTAGTGACG-3? (242–262) 5?-ACCATATCCGACAGGAACTGC-3? (348–328) 5?-ATTTCGGGAGTTAGTACTGGGCTAGTGGCC-3? (265–294) SLC26A5 (NM_198999) 5?-AAATTGCCGGCGCCTAT-3? (853–869) 5?-GCCCTAGAGGAAGTGTTCCAAC-3? (973–952) 5?-CCTTTAGAGTTCTTTGCGGTCGTAATGGG-3? (871–899) SLC26A6 (NM_022911) 5?-GATCCACTTCGGCTTCGTG-3? (600–618) 5?-AGACGAAGACCTGCACAGCTG-3? (685–665) 5?-TCACCTACCTGTCAGAACCTCTTGTCCG-3? (620–647) SLC26A7 (NM_052832) 5?-TGTTGCCACAGGCACCTTT-3? (294–312) 5?-ATAAGCCCAGCACGCTTGT-3? (412–394) 5?-ACATCCTTAATATCAGCCAACGCCGTGGA-3? (319–347) SLC26A8 (NM_052961) 5?-ATGGGCGTATTGGGTTTGG-3? (634–652) 5?-AGCCAGGTAAGCACTCATTGC-3? (702–682) 5?-CTTCATTGCCACTTACCTTCCGGAGTCT-3? (654–681) SLC26A9 (NM_052934) 5?-CCCGCTACGTGGTAGACAGA-3? (17–36) 5?-TGGGTATGTCCGGTCCTTCTT-3? (96–76) 5?-CCGCATACTCCCTTACCCTCTTCGACG-3? (38–64) SLC26A10 (NM_133489) 5?-CTCTACACTTCTTTCTTCCCCGTC-3? (166–189) 5?-GCTGAGTATGGCGAAAGTTCCT-3? (252–231) 5?-TCATCTACAGCTTGCTAGGTACTGGGAGACACC-3? (191–223) SLC26A11 (NM_173626) 5?-GCTGGCCTATGCTGAAGTGG-3? (198–217) 5?-AATACACGAAGCAGCCCATG-3? (274–255) 5?-CCGCCCCAGTATGGCCTCTACTCTG-3? (226–250) SLC27A1 (NM_198580) 5?-CGCTTCGATGGCTATGTCA-3? (1384–1402) 5?-CCTGAGAGGTAGGCGCTGT-3? (1472–1454) 5?-CCACCAGCAAGAAGATCGCCCACA-3? (1412–1435) SLC27A2 (NM_003645) 5?-CGGTGAACTGCTTCGGTATTT-3? (936–956) 5?-TCCTCGTAAGCCATTTCCCA-3? (1029–1010) 5?-AACTCACCACAGAAACCAAATGACCGTG-3? (961–988) SLC27A3 (NM_024330) 5?-TGCTTCCTGGCTTTACAAGCA-3? (1479–1499) 5?-CGAATTGGCTCTCCTGTGGT-3? (1553–1534) 5?-ATCTTCCCCTTCTCCTTGATTCGCTATGATGT-3? (1501–1532) SLC27A4 (NM_005094) 5?-GGTGGTGATTCGGAAGAAGTT-3? (921–941) 5?-CGGCACAGTTCACCAATGTA-3? (1016–997) 5?-CCCGGTTCTGGGACGATTGTATCAAGTA-3? (950–977) SLC27A5 (NM_012254) 5?-GGCGTGACAGTGATCCTGTATG-3? (1123–1144) 5?-TATGTGTCCGGTCCTCTGGTT-3? (1204–1184) 5?-CTCCTGCGGTACTTGTGTAACATTCCCCA-3? (1153–1181) SLC27A6 (NM_014031) 5?-TCAGCAGCTATCCTGGGAATT-3? (805–825) 5?-CCAAAACTGGCTTGCTGAAAA-3? (891–871) 5?-ATGTGTTGAGTTGGGTGCCACTTGTGTGTT-3? (831–860) SLC30A1 (NM_021194) 5?-CAGAACCCAGTGTGCTTTGAA-3? (1311–1331) 5?-TGCATCCTTTCCAGAAGGG-3? (1377–1359) 5?-CAATGTTGTGGGACACTACCACAAGCC-3? (1333–1359) SLC30A2 (NM_001004434) 5?-TGTTCTGTCTGTCCACATCGC-3? (948–968) 5?-GTGTGGAAGTGGAACTTCCCT-3? (1046–1026) 5?-AATACAGACGCCCAGGCTGTGCTGAA-3? (979–1004) SLC30A3 (NM_003459) 5?-CCTCCGAGACGTTCTTCGAAT-3? (852–872) 5?-GGCACCGACAACAGCGTAT-3? (938–920) 5?-CTCATGGAAGGTACCCCCCGCAAT-3? (874–897) SLC30A4 (NM_013309) 5?-TGGACTCCTGTGACAACTGCA-3? (275––295) 5?-TACAGAACGGCAGCAATGGTC-3? (362–342) 5?-ACAGAGAGAGATACTGAAGCAGAGAAAGGTGAAAGCC-3? (300–336) mRNA Expression Profiles of Human SLC Transporters 27

Table 3. (continued)

mRNA (GenBank No.) Forward primer (Position) Reverse primer (Position) Probe (Position)

SLC30A5 (NM_022902) 5?-ACTCTTGGCAGCATTGGTGTG-3? (1798–1818) 5?-AACAGAGTGGGTCAGCGATGA-3? (1876–1856) 5?-TCGTATCCACAGTTCTTATAGAGCAGTTTGGATG-3? (1820–1853) SLC30A6 (NM_017964) 5?-TCATTGGCTGGATCAGTGCA-3? (880–899) 5?-AGCCTGTTGGTCACATGAGCA-3? (959–939) 5?-TCGACGAGATGCCAATGAACAAATGG-3? (909–934) SLC30A7 (NM_133496) 5?-ATCTCGGGCTGGTTTAGGTCT-3? (64–84) 5?-AGGTTCAGGCACAGGAAGAAA-3? (137–117) 5?-TACTGTCCGACAAGACTTCCCGGAACCT-3? (86–113) SLC30A8 (NM_173851) 5?-TTACCAGATCCAGGCGACTGT-3? (510–530) 5?-TGATTGTGGCCAAGGCATC-3? (614–596) 5?-ATGATCATCGTTTCCAGCTGCGCA-3? (532–555) SLC30A9 (NM_006345) 5?-ACTGCTGCAGTCTTGGGAGTT-3? (1192–1212) 5?-ATGCCTAATAAGGTGCCCACA-3? (1307–1287) 5?-AATAGCAGCCACTTGCATGGGCCTTACT-3? (1215–1242) SLC30A10 (NM_018713) 5?-TGTTCGCAAACGTAGCAGG-3? (623–641) 5?-CACCTCTGATATTCAGAGCTTCAGAC-3? (721–696) 5?-TTCAACACCCAGAATGAGCCAGAAGACA-3? (649–676) SLC31A1 (NM_001859) 5?-GGACTCAAGATAGCCCGAGAG-3? (253–273) 5?-CTCAGCATCTGTTGCCCAA-3? (386–368) 5?-CTGCGTAAGTCACAAGTCAGCATTCGC-3? (280–306) SLC31A2 (NM_001860) 5?-TGTGTCACTTTGGCCAGTCTC-3? (272–292) 5?-ACCACACCAAGGAAAATCCAG-3? (377–357) 5?-AATCCATGTCATCCAGGTGGTCATCG-3? (294–319) SLC32A1 (NM_080552) 5?-AGGTCATCACGGATAACCTGC-3? (1103–1123) 5?-TTCCTGGAAGAGCGACTTCTC-3? (1236–1216) 5?-ATCCGCGCCGTGGTCAACATCTTT-3? (1132–1155) SLC33A1 (NM_004733) 5?-ATTGCTCTCACTGTGGCGTTC-3? (529–549) 5?-AACCCACATTTTCCCTGGAT-3? (634–615) 5?-TTTGTTTGAATTCTTGGCCGCCACTC-3? (552–577) SLC34A1 (NM_003052) 5?-AGCAGTTCTGTGTTCACCTCG-3? (1252–1272) 5?-GCCCTCTCAATGCTGATCAC-3? (1319–1300) 5?-CCATCACCCCACTCATCGGTCTTG-3? (1274–1297) SLC34A2 (NM_006424) 5?-CTGGACCATGAAGAATGTGACCTA-3? (1005–1028) 5?-AGATCCGGGAGGTGGAAATT-3? (1085–1066) 5?-AAGGAGAACATCGCCAAATGCCAGCA-3? (1030–1055) SLC34A3 (NM_080877) 5?-GTGTCTGTGCCCATCATCATG-3? (463–483) 5?-TGAAATTCATCCCGGTCCC-3? (557–539) 5?-CAACGTAGGCACATCCATCACCAGCA-3? (489–514) SLC37A1 (NM_018964) 5?-GCGCCTGCCGATTAGGTA-3? (366–383) 5?-AACAGGGCGGTGAAGGCT-3? (431–414) 5?-AACTTTCGGGATGCTCGCCAGCG-3? (390–412) SLC37A2 (NM_198277) 5?-ACGCCTGCTATCACATGTCCA-3? (98–118) 5?-TTGATCTGCTCCGAGCAGTTC-3? (176–156) 5?-AAGCCTATCAGTATCGTCAAGAGCCGTCTG-3? (121–150) SLC37A3 (NM_207113) 5?-GTGGAGATCTGGAGCAGCAA-3? (193–212) 5?-CAGTGTGCCGAGGAAAAGAG-3? (261–242) 5?-CATTTGTTCCCCAGTGCAGAGAAAGCG-3? (214–240) SLC37A4 (NM_001467) 5?-GGTTCATCACCAGCAGCCA-3? (149–167) 5?-TGTTGACCAGGCCAACCAG-3? (274–256) 5?-TCGGCAGCTTATGCTATCAGCAAGTTTG-3? (169–196) SLC39A1 (NM_014437) 5?-TGATGGAGCAGATCACACTGG-3? (374–394) 5?-GCCCATCATGCCAATGC-3? (487–471) 5?-TTACAAGGAGCAGTCAGGGCCGTCA-3? (396–420) SLC39A2 (NM_014579) 5?-GGAGCAGGGTTCATGCATATG-3? (172–192) 5?-TGCTGATCTGTTCTGCACCAT-3? (258–238) 5?-CTGCTGAAGCCCTGGAGGAAATTGAATC-3? (194–221) SLC39A3 (NM_144564) 5?-CACATCAGCACCGACTACCC-3? (235–254) 5?-AGGTCAGGATCAGCTGCTCC-3? (322–303) 5?-TGGCCGAAACCATCCTCCTGCT-3? (257–278) SLC39A4 (NM_017767) 5?-CATGTCAGGAGCGGGTCTT-3? (490–508) 5?-TCATAGGGACCTCGCTGCT-3? (583–565) 5?-ACGCCTTGCCGAGCCCTCAGTACTT-3? (515–539) SLC39A5 (NM_173596) 5?-TGGACCACTCATTGGCTGA-3? (434–452) 5?-GCCAAAATTGACCAGCAGCT-3? (504–485) 5?-CACCTGAATGAGGATTGTCTGAACGGCT-3? (454–481) SLC39A6 (NM_012319) 5?-AGACCTGGAAAACTCTTCCCC-3? (607–627) 5?-TCACCCGGCTCTTTGATGT-3? (679–661) 5?-AAGATGTAAGCAGCTCCACTCCACCCA-3? (629–655) SLC39A7 (NM_006979) 5?-AGGCATCAAGCAGGACCTG-3? (369–387) 5?-TGAGATCAGCACTGTGGCC-3? (438–420) 5?-ATGCTGTCACTCTCTGGGCTTATGCACTG-3? (389–417) SLC39A8 (NM_022154) 5?-AATGCTACCCAAATAACCAGCTC-3? (262–284) 5?-TTTGTGCTTGGGCCGATC-3? (360–343) 5?-TCATCTGTCCAGCAGTCTTACAGCAATTGA-3? (296–325) SLC39A9 (NM_018375) 5?-TGGTAACTCCCATGTGCATTC-3? (375–395) 5?-AGCGTGGTGGTGATTTTGG-3? (449–431) 5?-ACGATCCAGAAGCAGCAAGGTCTAGCAAT-3? (401–429) SLC39A10 (NM_020342) 5?-CAATACACCAGATTCTGACTGGCT-3? (1653–1676) 5?-TAAGTCGATCTTCAGAAACAACCGA-3? (1732–1708) 5?-CAACTCAAGCCTCTTGCCGGAACTG-3? (1678–1702) SLC39A11 (NM_139177) 5?-TTGGAGCGGCTTTTGTCTACT-3? (260–280) 5?-TAGAGCCGAAGTTCAGTGCCA-3? (355–335) 5?-ATGCCTCACTTGGGTGCAGCAGAAGA-3? (295–320) SLC39A12 (NM_152725) 5?-CCAGGCAGTACTTTGACACTTCTC-3? (512–535) 5?-TCATTAGCACCTTCACTGCTCA-3? (605–584) 5?-AAGCCAGTGTATGGAAACCAAAACGCTG-3? (537–564) SLC39A13 (NM_152264) 5?-TGAGCAAGAAGATCGGGCTC-3? (725–744) 5?-AAAGTCGCCCACCTCATGG-3? (798–780) 5?-ATGGCCATCCTCCTGCATGAGATCC-3? (754–778) SLC39A14 (NM_015359) 5?-ATCGCCCTGTCCATTGGAA-3? (571–589) 5?-ATAAAAGCCCCCAAACACCA-3? (696–677) 5?-CTGTCTAACGCGCTATTCCAGCTCATCC-3? (595–622) SLC40A1 (NM_014585) 5?-TATTGTCCCGGAGACAAGTCC-3? (1320–1340) 5?-AGCAATGACGCCTGCAAAC-3? (1392–1374) 5?-AATCTGTGCCCATAATCTCTGTCAGTCTGC-3? (1343–1372) SLC41A1 (NM_173854) 5?-TCATCATTGGCTCTCGCAAG-3? (716–735) 5?-TCAGTTCCAGGTAGAGTCCCCA-3? (844–823) 5?-TTGGGATCAACCCAGACAACGTGG-3? (737–760) SLC41A2 (NM_032148) 5?-CAAACATCCAGCCACAAGAAC-3? (855–875) 5?-AGAATAAGGCCCCCAATGC-3? (944–926) 5?-ACTCAGGCTGGGAGCCTGTCATAACA-3? (884–909) SLC41A3 (NM_001008485) 5?-TGGCGATATTTACCCCCGTC-3? (944–963) 5?-AGGTTGAGATTCGGCTGGTCT-3? (1018–998) 5?-TATGTGGTGTTGGTGGCAATCTGGTG-3? (965–990) The positions of the primers and probes were counted from the position of the initiation codon.

PCR reaction, the TaqMan One-Step RT-PCR Master Mix Rea- Results and Discussion gents Kit (Applied Biosystems) containing 300 nM forward primer, 900 nM reverse primer, and 200 nM TaqMan probe In this study, the mRNA expression levels of 173 human was used at 20 mL/tube. The RT-PCR assay was performed us- SLC family transporters in adult human tissues were investigat- ing the Applied Biosystems 7500 Fast Real-Time PCR System ed. Analysis was conducted by RT-PCR using the Applied (Applied Biosystems) with the following profile: 1 cycle at Biosystems 7500 Fast Real-Time PCR System in the presence of 489C for 30 min, 1 cycle at 959C for 10 min, and 40 cycles the TaqMan probe. In order to prepare the transporter calibra- each at 959C for 15 sec and 609C for 1 min. The threshold tion curves, the total RNA obtained from the tissue exhibiting cycle (Ct) was calculated by the instrument's software (7500 the highest mRNA expression levels was used for the individual Fast System ver. 1.3.1). transporter isoforms. When preparing the calibration curves, Data analysis: TherelativeexpressionofeachmRNA various amounts ranging from 0.768 to 60,000 pg of total was calculated by the DCt method (where DCt is the value RNA were used. The lower limit of quantification for each obtained by subtracting the Ct value of PPIA mRNA from the mRNA ranged between 0.768 and 2,400 pg of total RNA per Ct value of the target mRNA), as employed in previous stu- 20 mL of reaction mixture. The upper limit of quantification dies.9,12) Specifically, the amount of target mRNA relative to for each mRNA was greater than 60,000 pg of total RNA per PPIAmRNAisexpressedas2－(DCt). Data are expressed as the 20 mL of reaction mixture. In the present study, PPIA was ratio of the target mRNA to PPIA mRNA. Using many target selected as the endogenous control, since it showed low RNAs and PPIA mRNA from the same human liver total RNA, variability and was used as an endogenous control in our previ- it was confirmed that there were no substantial differences in ous studies.9,12–14). The process used to select the most suitable the results obtained using the ABI PRISM 7700 Sequence De- housekeeping gene has been described in detail in our previous tector System (Applied Biosystems) employed in our previous studies.12,15) The highest and second highest Ct values for PPIA studies9,12) and the 7500 Fast Real-Time PCR System (Applied in various tissues were 22.33 in the mammary gland and 21.02 Biosystems) employed in the present study (data not shown). in skeletal muscle, respectively. Furthermore, similar to the 28 Masuhiro NISHIMURA and Shinsaku NAITO

Table 4. Expression of Human SLC Transporter mRNAs in Various Tissues

Tissue SLC8A1 SLC8A2 SLC8A3 SLC9A1 SLC9A2 SLC9A3 SLC9A4 SLC9A5 SLC9A6 SLC9A7

Adrenal gland 0.0334 0.00910 0.00135 0.0575 0.00105 0.00809 BLQ 0.00280 0.0684 0.0456 Bladder 0.599 0.0207 0.00334 0.0535 0.00235 0.00432 0.000551 0.00144 0.0593 0.0132 Bone marrow 0.0396 0.0909 0.00949 0.0433 0.00134 0.00936 0.0000155 0.0120 0.159 0.0194 Brain 0.248 0.371 0.0257 0.0497 0.00359 0.0215 0.0000863 0.0280 0.277 0.0822 Colon 0.105 0.0166 0.000717 0.0845 0.0573 0.145 0.000131 0.00281 0.0437 0.0137 Heart 3.41 0.00206 0.000880 0.0718 0.00111 0.00572 BLQ 0.00560 0.146 0.0331 Kidney 0.132 0.000140 0.000175 0.0270 0.0145 1.04 0.0105 0.00215 0.0415 0.0338 Liver 0.0225 0.0000496 0.0000469 0.00942 0.0000287 0.00186 BLQ 0.000546 0.0352 0.0274 Lung 0.107 0.000216 0.00292 0.0595 0.000745 0.00580 0.0000257 0.00680 0.0638 0.0148 Mammary gland 0.0552 0.000422 0.000298 0.0661 0.00208 0.00391 0.000401 0.00187 0.00367 0.418 Ovary 0.0456 0.000334 0.000133 0.0292 0.0000687 0.0102 0.000149 0.00609 0.0665 0.0912 Pancreas 0.00521 0.0330 0.000614 0.0390 0.0000822 0.00290 BLQ 0.00288 0.0308 0.0303 Peripheral leukocytes 0.125 0.000246 0.000581 0.0537 0.0000499 0.00380 BLQ 0.00198 0.0689 0.0447 Placenta 0.120 0.000343 0.000318 0.503 0.0000985 0.00776 0.0000459 0.00271 0.0638 0.0192 Prostate 0.193 0.00724 0.00138 0.0872 0.0361 0.0254 0.0000663 0.00526 0.0436 0.202 Retina 0.103 0.00962 0.0156 0.0480 0.00221 0.0157 0.0000932 0.00849 0.102 0.0472 Salivary gland 0.00457 0.000247 0.000326 0.815 0.0157 0.00999 0.001829 0.00255 0.0542 0.101 Skeletal muscle 0.0629 0.00161 0.151 0.0767 0.0912 0.0112 BLQ 0.0176 0.286 0.448 Small intestine 0.0786 0.00582 0.00122 0.0696 0.00664 0.170 0.000330 0.00195 0.0489 0.0219 Smooth muscle 1.09 0.0274 0.00224 0.0326 0.00121 0.00694 0.000176 0.00214 0.0604 0.0147 Spinal cord 0.146 0.0196 0.0152 0.0337 0.00776 0.0125 0.000495 0.0105 0.173 0.0944 Spleen 0.137 0.0000736 0.000309 0.0178 0.0000663 0.00317 BLQ 0.0335 0.0693 0.0559 Stomach 0.122 0.00739 0.00169 0.209 0.102 0.207 0.0872 0.00185 0.0442 0.0604 Testis 0.0346 0.0160 0.00155 0.0556 0.0552 0.0387 0.00232 0.0361 0.138 0.0228 Thymus 0.0183 0.000892 0.000488 0.0249 0.000649 0.00481 0.0000711 0.000990 0.0398 0.0324 Thyroid gland 0.0143 0.000318 0.000233 0.0579 0.00515 0.00635 0.000141 0.00229 0.0713 0.0470 Trachea 0.0469 0.00125 0.00130 0.130 0.00331 0.0256 0.00109 0.00404 0.0797 0.0579 Uterus 0.207 0.0310 0.00120 0.0526 0.000502 0.00744 0.0000938 0.00367 0.0629 0.00891

BLQ, below the limit of quantification. Data are expressed as the ratio of the target mRNA to PPIA mRNA. Experiments were performed in duplicate. The highest values among the various tissues are shown in boxes.

Table 4. (continued)

Tissue SLC9A8 SLC9A9 SLC9A10 SLC9A11 SLC11A1 SLC11A2 SLC12A1 SLC12A2 SLC12A3 SLC12A4

Adrenal gland 0.0397 0.0349 0.0000214 0.0000099 0.0148 0.00972 0.000109 0.127 0.000140 0.0223 Bladder 0.0266 0.247 0.000248 BLQ 0.00570 0.0115 0.0000803 0.0497 0.000807 0.0928 Bone marrow 0.0181 0.0415 0.000148 BLQ 0.0494 0.0131 0.000405 0.0333 0.00176 0.00657 Brain 0.0147 0.0282 BLQ 0.0000213 0.00244 0.0150 0.000686 0.141 0.000320 0.00586 Colon 0.0166 0.0325 0.0000842 BLQ 0.000261 0.00755 0.0000286 0.293 0.000620 0.0105 Heart 0.0162 0.0612 0.00404 BLQ 0.00156 0.00812 0.0000875 0.0730 0.000253 0.0329 Kidney 0.0169 0.00795 0.000131 BLQ 0.00148 0.0157 1.44 0.0329 0.732 0.0103 Liver 0.00755 0.0454 BLQ BLQ 0.00263 0.00861 0.000277 0.0114 0.000110 0.00609 Lung 0.0135 0.0561 0.000192 0.0000417 0.0909 0.0142 0.000169 0.0805 0.00109 0.0287 Mammary gland 0.0369 0.00798 0.000177 BLQ 0.000205 BLQ 0.0000291 0.637 0.00108 0.0257 Ovary 0.0150 0.125 0.0000438 0.0000239 0.00124 0.00687 0.0000360 0.0875 0.000112 0.0783 Pancreas 0.0160 0.0103 0.000219 BLQ 0.00190 0.0197 0.0000828 0.0577 0.000970 0.00514 Peripheral leukocytes 0.0260 0.0467 0.0000231 BLQ 0.316 0.00834 0.000468 0.0373 0.00354 0.00682 Placenta 0.0433 0.0797 0.000307 BLQ 0.0209 0.0330 BLQ 0.0227 0.00465 0.0842 Prostate 0.0299 0.0797 0.000231 0.0000135 0.00304 0.0368 0.0000114 0.402 0.000880 0.0225 Retina 0.0283 0.0964 0.000131 0.0000510 0.00476 0.0213 0.00162 0.197 0.000793 0.101 Salivary gland 0.0240 0.0135 0.0000163 BLQ 0.00106 0.0205 BLQ 0.418 0.000780 0.00814 Skeletal muscle 0.0819 0.0638 0.000232 BLQ 0.00105 0.0526 0.000203 0.257 0.000252 0.0808 Small intestine 0.0180 0.0475 0.000118 BLQ 0.000295 0.00852 0.0000110 0.307 0.000877 0.00870 Smooth muscle 0.0202 0.289 0.000217 BLQ 0.00364 0.0143 0.0000070 0.600 BLQ 0.148 Spinal cord 0.0469 0.138 0.000135 0.000146 0.0122 0.0205 0.000710 0.260 0.000930 0.0275 Spleen 0.0266 0.132 0.0000673 0.0000325 0.0226 0.00433 0.0000213 0.0379 0.00657 0.00809 Stomach 0.0308 0.0524 0.0000701 BLQ 0.00350 0.0105 0.0000124 0.339 0.000705 0.0128 Testis 0.0756 0.0178 0.0842 0.0147 0.00146 0.0116 0.00226 0.135 0.00258 0.0275 Thymus 0.0146 0.0725 0.0000543 BLQ 0.00141 0.00820 0.0000239 0.0256 0.00393 0.0100 Thyroid gland 0.0278 0.0288 0.000750 BLQ 0.00338 0.0206 BLQ 0.0698 0.000338 0.0249 Trachea 0.0533 0.0484 0.000146 0.0000951 0.00523 0.0250 0.0000277 1.72 0.00189 0.0212 Uterus 0.0161 0.0451 0.0000426 0.0000057 0.00141 0.0173 0.000388 0.0461 0.000237 0.0315

Table 4. (continued)

Tissue SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9 SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5

Adrenal gland 0.00399 0.00919 0.0233 0.00690 0.0271 0.0000266 BLQ 0.000914 0.0105 0.0443 Bladder BLQ 0.0941 0.0379 0.00876 0.0819 BLQ 0.0000652 BLQ 0.0149 BLQ Bone marrow 0.139 0.0713 0.0377 0.00592 0.0409 BLQ 0.0000208 BLQ 0.0268 BLQ Brain 0.423 0.0275 0.00590 0.0128 0.0179 0.0000056 0.0000257 0.00469 0.0372 0.0179 Colon 0.000132 0.0143 0.0454 0.0210 0.0298 0.000186 0.0222 BLQ 0.0112 BLQ Heart 0.00126 0.0741 0.253 0.00218 0.00894 0.0000206 0.0000073 BLQ 0.0234 BLQ Kidney 0.000139 0.0893 0.108 0.0105 0.0271 0.233 0.633 0.431 0.00832 0.00535 Liver 0.000158 0.0115 0.0511 0.0206 0.0147 0.000106 0.00322 0.00288 0.00246 1.53 Lung 0.000874 0.0273 0.0322 0.0135 0.0238 0.0000213 0.00156 0.00214 0.0103 BLQ Mammary gland 0.000139 0.0347 0.0540 0.0196 0.299 BLQ 0.0186 BLQ 0.00724 BLQ Ovary 0.000277 0.0589 0.0179 0.00942 0.0244 BLQ BLQ BLQ 0.0177 0.00366 Pancreas 0.000614 0.00373 0.0360 0.0340 0.0266 BLQ 0.000610 BLQ 0.000782 0.00768 Peripheral leukocytes 0.000136 0.194 0.0336 0.000924 0.164 BLQ 0.0000078 BLQ 0.00699 BLQ Placenta 0.000667 0.0206 0.0113 0.0600 0.0518 BLQ 0.0000041 0.0252 0.176 BLQ Prostate 0.0000985 0.0469 0.0428 0.0344 0.0231 BLQ 0.00410 0.00840 0.0150 BLQ Retina 0.106 0.125 0.0971 0.0202 0.0233 BLQ 0.00372 0.000927 0.142 0.00678 Salivary gland 0.0000670 0.00184 0.0240 0.0811 0.0216 0.0000596 0.173 0.00249 0.00395 1.43 Skeletal muscle BLQ 0.147 0.0344 0.00122 0.0150 0.0000298 0.0000192 0.00657 0.0373 BLQ Small intestine 0.000134 0.0169 0.0214 0.0264 0.0314 0.00271 0.378 0.000914 0.00253 BLQ Smooth muscle 0.0000140 0.0559 0.0196 0.00223 0.0643 BLQ 0.0000097 BLQ 0.0250 BLQ Spinal cord 0.0583 0.0266 0.0142 0.00680 0.0513 BLQ 0.0000805 0.0112 0.0401 0.00532 Spleen 0.000110 0.0390 0.0556 0.00174 0.0369 BLQ BLQ BLQ 0.00955 0.00385 Stomach 0.0000397 0.0263 0.0439 0.0369 0.0250 0.0000024 0.00749 0.00322 0.00755 BLQ Testis 0.00549 0.284 0.111 0.0451 0.0289 0.000294 0.00240 0.00158 0.0494 0.0456 Thymus 0.000262 0.0175 0.0326 0.00290 0.0208 BLQ 0.000311 0.000585 0.00885 0.000394 Thyroid gland 0.0000268 0.0501 0.0335 0.0884 0.0284 0.0000028 0.00552 BLQ 0.0118 0.00391 Trachea 0.000269 0.0199 0.0723 0.0404 0.0404 BLQ 0.225 0.00461 0.00936 0.00989 Uterus 0.000151 0.0187 0.0219 0.00690 0.0183 0.0000057 0.000125 0.00135 0.0128 0.00331

Table 4. (continued)

Tissue SLC14A1 SLC14A2 SLC16A1 SLC16A2 SLC16A3 SLC16A4 SLC16A5 SLC16A6 SLC16A7 SLC16A8

Adrenal gland 0.00602 0.000691 0.0313 0.143 0.137 0.0235 0.00709 0.118 0.140 0.00549 Bladder 0.101 0.000847 0.0499 0.0309 0.310 0.0285 0.0376 0.00347 0.0808 0.00611 Bone marrow 0.451 0.000301 0.0183 0.00122 1.69 0.00484 0.0421 0.0961 0.0775 0.00242 Brain 0.0524 0.000827 0.0266 0.0294 0.0751 0.00666 0.00274 0.0408 0.0619 0.0161 Colon 0.00315 0.0115 0.0682 0.0125 0.395 0.00907 0.0640 0.00749 0.0427 0.00535 Heart 0.00353 0.000705 0.314 0.0379 0.234 0.0208 0.0487 0.0107 3.40 0.0117 Kidney 0.0453 0.0296 0.0243 0.0643 0.182 0.570 0.0842 0.0173 0.231 0.00404 Liver BLQ 0.0000463 0.0474 0.186 0.0604 0.0205 0.0223 0.00962 0.0448 0.00232 Lung 0.00551 0.000730 0.0121 0.0190 0.936 0.0427 0.135 0.0554 0.0736 0.00413 Mammary gland 0.0163 0.000362 0.0199 0.00936 0.563 0.0398 0.0552 0.0670 0.0791 0.0224 Ovary BLQ 0.000523 0.0470 0.0693 0.125 0.0629 0.0625 0.00779 0.0262 0.0108 Pancreas BLQ 0.000730 0.00617 0.0187 0.0185 0.00246 0.0185 0.00716 0.236 0.00189 Peripheral leukocytes 0.0291 0.000577 0.00949 0.000294 3.47 0.000977 0.0754 0.402 0.0991 0.00186 Placenta 0.00580 0.00121 0.0915 0.0442 4.99 1.15 0.216 0.0418 0.00592 0.00498 Prostate 0.956 0.00197 0.0713 0.0387 0.549 0.0175 0.108 0.0256 0.0322 0.0290 Retina BLQ 0.00143 0.169 0.0389 3.33 0.122 0.0363 0.174 0.0287 0.350 Salivary gland 0.00501 0.000717 0.00387 0.0238 0.325 0.0108 0.0277 0.00151 0.0559 0.0260 Skeletal muscle 0.00380 0.0157 0.584 0.0363 16.8 0.0301 0.103 0.0265 0.351 0.0185 Small intestine 0.00632 0.0400 0.0447 0.0109 0.247 0.0167 0.0887 0.0283 0.0285 0.00363 Smooth muscle 0.0310 0.000750 0.0634 0.0313 0.261 0.0209 0.0235 BLQ 0.107 0.00685 Spinal cord 0.815 0.000516 0.0540 0.0382 0.231 0.0436 0.00910 0.0550 0.0606 0.0247 Spleen 0.0282 0.000553 0.0183 0.00501 0.683 0.0169 0.0245 0.134 0.177 0.00375 Stomach 0.00446 0.00105 0.0652 0.0156 0.500 0.0158 0.0723 0.0103 0.122 0.00218 Testis 0.00257 0.0232 0.206 0.0126 1.34 0.0480 0.0511 0.0706 0.318 0.0224 Thymus 0.0548 0.00115 0.0182 0.0235 0.195 0.00201 0.00891 0.0188 0.0533 0.00271 Thyroid gland 0.00206 0.00605 0.00739 0.0769 0.415 0.0427 0.0647 0.0448 0.0587 0.00809 Trachea 0.0317 0.000782 0.0129 0.0249 1.39 0.0201 0.152 0.0480 0.0866 0.0187 Uterus 0.00284 0.000456 0.0604 0.0537 0.274 0.0142 0.0412 0.0257 0.0461 0.00837

Table 4. (continued)

Tissue SLC16A9 SLC16A10 SLC16A11 SLC16A12 SLC16A13 SLC16A14 SLC17A1 SLC17A2 SLC17A3 SLC17A4

Adrenal gland 5.64 0.0221 0.00244 0.00377 0.00537 0.0342 0.000707 0.0000150 0.00312 BLQ Bladder 0.0579 BLQ 0.00139 0.000669 0.00273 0.0264 BLQ BLQ BLQ BLQ Bone marrow 0.174 0.00465 0.00135 0.000523 0.00576 0.0354 BLQ BLQ BLQ BLQ Brain 0.119 0.00433 0.00879 0.00124 0.00328 0.0836 BLQ BLQ BLQ BLQ Colon 0.200 0.00524 0.00291 0.000346 0.00757 0.0160 BLQ BLQ BLQ 0.00191 Heart 0.139 0.0175 0.00552 0.0165 0.00338 0.0474 BLQ BLQ BLQ BLQ Kidney 9.75 0.0379 0.00662 0.148 0.0404 0.00897 2.86 0.000710 1.31 0.000166 Liver 0.0445 0.0113 0.0209 0.000402 0.113 0.0237 0.241 0.149 0.193 0.0218 Lung 0.0513 0.00556 0.0146 0.00526 0.00704 0.0407 BLQ BLQ 0.000753 BLQ Mammary gland 0.102 BLQ 0.00613 0.000149 0.00294 0.0109 0.0616 BLQ BLQ BLQ Ovary 0.662 0.00244 0.0125 0.00135 0.00306 0.0941 0.00200 BLQ 0.00348 BLQ Pancreas 0.111 0.0718 0.0167 0.0192 0.00136 0.0155 BLQ 0.000142 BLQ 0.00227 Peripheral leukocytes BLQ 0.00416 0.00452 BLQ 0.00826 0.00198 BLQ BLQ 0.00193 BLQ Placenta 0.00749 0.0203 0.000833 0.0208 0.0103 0.00269 BLQ BLQ BLQ 0.0000230 Prostate 0.465 0.00680 0.00923 0.00195 0.00765 0.0600 BLQ BLQ BLQ BLQ Retina 0.202 0.0116 0.0133 0.0302 0.00258 0.580 0.00287 BLQ 0.00476 BLQ Salivary gland 0.0947 0.0248 0.0408 0.000310 0.0112 0.237 BLQ BLQ BLQ BLQ Skeletal muscle 0.566 0.179 0.00457 0.00979 0.00279 0.00789 BLQ BLQ BLQ BLQ Small intestine 0.0350 0.0120 0.00562 0.000264 0.0207 0.0213 BLQ BLQ BLQ 0.00196 Smooth muscle 0.132 BLQ 0.00161 0.00103 0.000970 0.0306 BLQ BLQ BLQ 0.0000042 Spinal cord 0.710 0.000271 0.0116 0.00452 0.00271 0.0367 BLQ BLQ 0.000337 BLQ Spleen 1.40 0.00675 0.00393 0.000188 0.0102 0.0401 BLQ BLQ BLQ BLQ Stomach 0.0361 0.00491 0.00180 0.000437 0.00391 0.0158 BLQ BLQ BLQ 0.0000456 Testis 1.02 0.0270 0.00552 0.0128 0.00430 0.0238 0.00876 0.000234 0.00858 0.0000535 Thymus 0.0252 0.0240 0.00354 0.000658 0.00685 0.00900 0.000307 BLQ BLQ BLQ Thyroid gland 0.493 0.0110 0.0515 0.00832 0.0112 0.0221 BLQ BLQ BLQ 0.0000060 Trachea 0.578 0.00508 0.0313 0.00132 0.0104 0.154 BLQ BLQ BLQ BLQ Uterus 0.497 BLQ 0.00481 0.00236 0.00519 0.0385 0.00206 BLQ BLQ 0.0000072

Table 4. (continued)

Tissue SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC18A1 SLC18A2 SLC18A3 SLC19A1 SLC19A2 SLC19A3

Adrenal gland 0.0701 BLQ 0.000905 0.0000539 0.0224 0.0175 0.000138 0.0401 0.0788 0.00812 Bladder 0.187 BLQ 0.00314 0.000170 0.0000082 0.00789 0.0000935 0.0126 0.0733 0.101 Bone marrow 0.171 BLQ 0.218 BLQ 0.0000773 0.00458 0.000231 0.0786 0.0238 0.00639 Brain 0.0944 0.000766 0.927 0.000899 0.000128 0.000569 0.000255 0.0526 0.0200 0.00800 Colon 0.0967 BLQ 0.00131 0.000529 0.00105 0.00285 0.00119 0.0318 0.0190 0.0186 Heart 0.141 0.0000189 0.00556 BLQ 0.0000305 0.00100 0.000162 0.00982 0.294 0.0118 Kidney 0.399 BLQ 0.000408 0.0000435 0.0000054 0.000186 BLQ 0.0213 0.0577 0.0120 Liver 0.162 BLQ 0.000251 0.000462 0.0000091 0.00191 BLQ 0.0407 0.0398 0.0354 Lung 0.167 BLQ 0.000419 0.000105 0.000170 0.0157 0.0000456 0.0947 0.0479 0.0253 Mammary gland 0.115 BLQ 0.000138 0.000116 0.0000287 0.00350 0.00132 0.0250 0.0808 0.0941 Ovary 0.0839 BLQ 0.000334 0.000112 BLQ 0.00996 BLQ 0.0387 0.0686 0.00673 Pancreas 0.0686 0.0000343 0.000380 0.0000179 BLQ 0.00404 0.000296 0.0237 0.0658 0.00379 Peripheral leukocytes 0.147 BLQ 0.0000469 BLQ 0.000373 0.00195 0.0000314 0.245 0.0397 BLQ Placenta 0.540 BLQ 0.000282 0.000886 0.0000180 0.000365 0.00133 0.155 0.500 0.540 Prostate 0.311 BLQ 0.000691 0.000174 0.000700 0.0385 0.000324 0.0458 0.0931 0.000865 Retina 0.278 0.000337 0.155 0.00203 0.0000258 0.00263 0.00126 0.0462 0.106 0.0174 Salivary gland 0.451 BLQ 0.000278 0.0000256 0.0000276 0.000178 0.000126 0.0181 0.0364 0.00331 Skeletal muscle 0.243 BLQ 0.00562 0.000112 BLQ 0.000940 0.0000487 0.0355 2.69 0.00832 Small intestine 0.115 BLQ 0.00216 0.000308 0.00175 0.00314 0.00120 0.0984 0.0256 0.0181 Smooth muscle 0.143 BLQ 0.00328 0.0000405 0.0000155 0.00787 0.0000619 0.00975 0.121 0.00515 Spinal cord 0.0938 0.00115 0.000383 0.000534 0.000265 0.000126 0.0190 0.0310 0.0472 0.00673 Spleen 0.127 BLQ 0.0000659 0.0000099 0.000482 0.000614 0.0000119 0.0401 0.0256 BLQ Stomach 0.122 BLQ 0.00160 0.0000246 0.000456 0.00814 0.000365 0.0195 0.0445 0.00910 Testis 0.307 0.0000243 0.00345 0.00129 0.000213 0.00427 0.000251 0.0451 0.144 0.00150 Thymus 0.0748 BLQ 0.000478 0.00103 0.0000384 0.00714 0.0000168 0.0169 0.0199 0.00419 Thyroid gland 0.308 BLQ 0.00130 0.0000176 0.000127 0.000169 0.0000184 0.0290 0.0698 0.00119 Trachea 0.206 BLQ 0.00208 BLQ 0.0000590 0.00265 0.000282 0.0201 0.127 0.00929 Uterus 0.0802 BLQ 0.00158 0.000106 0.0000257 0.0167 0.0000075 0.0173 0.0379 0.00294

Table 4. (continued)

Tissue SLC20A1 SLC20A2 SLC23A1 SLC23A2 SLC23A3 SLC24A1 SLC24A2 SLC24A3 SLC24A4 SLC24A5

Adrenal gland 0.0373 0.00566 BLQ 0.181 0.00172 0.00379 0.0328 0.00929 0.00286 0.00298 Bladder 0.241 0.0656 BLQ 0.0612 BLQ 0.0227 0.000144 0.0462 0.00233 0.00213 Bone marrow 0.156 0.00458 BLQ 0.00885 0.00186 0.00657 0.0928 0.0215 0.0326 0.00505 Brain 0.134 0.0180 BLQ 0.0531 BLQ 0.00339 0.319 0.0467 0.0412 0.0102 Colon 0.0825 0.0145 0.0158 0.00407 0.00267 0.00481 0.000433 0.0267 0.00104 0.00120 Heart 0.0509 0.0938 BLQ 0.0122 BLQ 0.00136 0.00209 0.0120 0.00169 0.00385 Kidney 0.0696 0.0166 0.262 0.0133 0.131 0.0148 0.000419 0.00247 0.000188 0.00282 Liver 0.0791 0.00955 0.0439 0.0286 0.000730 0.00364 0.0000238 0.00215 0.00149 0.0000615 Lung 0.147 0.0159 0.00135 0.0196 0.00180 0.0110 0.000102 0.0175 0.00515 0.00252 Mammary gland 0.0433 0.574 BLQ 0.0245 0.0836 0.00309 0.000610 0.0173 0.000353 0.00306 Ovary 0.0725 0.0137 BLQ 0.124 0.00295 0.0233 0.000103 0.0349 0.00129 0.000355 Pancreas 0.0623 0.0341 0.00387 0.00514 BLQ 0.00514 0.0000958 0.00202 0.0000805 0.00803 Peripheral leukocytes 0.276 0.00846 BLQ 0.0234 0.000753 0.0103 0.000246 0.00319 0.0508 0.00146 Placenta 0.966 0.0282 BLQ 0.274 0.00352 0.0194 0.000485 0.0209 0.00809 0.000280 Prostate 0.0668 0.0226 0.0172 0.0378 0.00238 0.0126 0.000391 0.0300 0.00136 0.00328 Retina 0.184 0.146 BLQ 0.755 0.00240 0.365 0.0451 0.0306 0.0364 0.245 Salivary gland 0.0335 0.149 0.00322 0.0105 0.00129 0.00592 0.000442 0.0162 0.000683 0.000807 Skeletal muscle 0.319 0.646 BLQ 0.0261 BLQ 0.00861 0.00118 0.396 0.00395 0.000871 Small intestine 0.101 0.0176 0.0918 0.0228 0.0165 0.00752 0.0000694 0.0248 0.00144 0.00206 Smooth muscle 0.150 0.0629 BLQ 0.0404 0.00187 0.00910 0.0000945 0.0518 0.00121 0.00709 Spinal cord 0.111 0.0440 BLQ 0.0767 0.000518 0.00779 0.245 0.0181 0.0981 0.0205 Spleen 0.163 0.00474 BLQ 0.0268 0.00185 0.0124 0.00350 0.00709 0.0162 0.00191 Stomach 0.0718 0.0141 0.00105 0.0114 0.00340 0.00989 0.000233 0.0123 0.000573 0.00419 Testis 0.190 0.0428 0.000934 0.0217 BLQ 0.0411 0.00588 0.0119 0.0173 0.0265 Thymus 0.0954 0.00652 0.00626 0.0110 0.000561 0.00568 0.0000554 0.00446 0.00162 0.000892 Thyroid gland 0.0533 0.114 BLQ 0.0608 0.00137 0.0254 0.0000299 0.0151 0.000672 0.00221 Trachea 0.310 0.0356 0.00714 0.0199 BLQ 0.00770 0.000146 0.0100 0.00171 0.00130 Uterus 0.0458 0.0183 BLQ 0.0221 0.00231 0.0148 0.00843 0.120 0.000777 0.000856

Table 4. (continued)

Tissue SLC24A6 SLC25A1 SLC25A2 SLC25A3 SLC25A4 SLC25A5 SLC25A6 SLC25A7 SLC25A8 SLC25A9

Adrenal gland 0.454 0.0360 0.000456 1.17 0.0299 0.908 2.11 0.0163 0.0556 0.00187 Bladder 0.0623 0.0105 0.000105 0.993 0.168 0.821 2.17 0.000319 0.0358 0.00113 Bone marrow 0.145 0.00347 0.000640 0.818 0.00300 0.688 1.34 0.000185 0.382 0.00252 Brain 0.0349 0.00578 0.000434 0.557 0.0736 0.483 1.01 0.000472 0.0123 0.00205 Colon 0.0557 0.0212 0.000356 0.758 0.0427 1.14 2.01 0.000818 0.0370 0.00106 Heart 0.0445 0.0210 0.000115 5.12 3.24 0.688 0.976 0.00231 0.0451 0.00955 Kidney 0.0522 0.0554 0.000228 1.07 0.0569 1.77 2.08 0.000101 0.0257 0.000937 Liver 0.0540 0.0738 0.000231 0.717 0.0270 1.56 0.660 0.0000320 0.0342 0.000380 Lung 0.109 0.00894 0.000531 0.601 0.0236 0.574 1.16 0.000156 0.129 0.00139 Mammary gland 0.128 0.00936 BLQ 3.12 0.0235 0.486 1.01 0.000506 0.100 0.000184 Ovary 0.339 0.0176 0.000531 0.626 0.0273 0.511 2.39 0.000348 0.00826 0.000631 Pancreas 0.0759 0.0281 0.000437 0.997 0.0238 3.07 3.90 0.000309 0.0298 0.000686 Peripheral leukocytes 0.170 0.00602 0.00141 0.862 0.00503 0.688 2.56 0.0000307 0.480 0.00375 Placenta 0.168 0.0304 0.00478 1.06 0.0497 1.20 2.48 0.000605 0.0928 0.00205 Prostate 0.0981 0.0475 0.000443 0.917 0.0469 0.651 2.15 0.000452 0.0421 0.00177 Retina 0.0499 0.00829 0.000700 0.963 0.232 0.648 2.11 0.000492 0.0470 0.00239 Salivary gland 0.0565 0.0242 0.000490 1.04 0.0504 1.55 2.66 0.000688 0.0822 0.00156 Skeletal muscle 0.124 0.0209 0.000480 8.94 7.21 0.911 2.48 0.000836 0.609 2.59 Small intestine 0.0573 0.0391 0.00163 1.18 0.0185 1.53 1.81 0.0000819 0.0816 0.00212 Smooth muscle 0.0415 0.0157 0.000219 1.23 0.219 0.796 2.53 0.000242 0.0130 0.00134 Spinal cord 0.0494 0.0156 0.000691 0.449 0.0495 0.390 0.930 0.000336 0.0328 0.00138 Spleen 0.142 0.0102 0.000614 0.595 0.0157 0.683 2.07 0.0000822 0.412 0.00199 Stomach 0.0480 0.0153 0.000394 1.18 0.0567 1.19 2.17 0.0000558 0.0600 0.000950 Testis 0.151 0.0255 0.0203 0.667 0.0649 0.590 1.02 0.00164 0.0508 0.00955 Thymus 0.107 0.00648 0.000258 0.390 0.00600 0.871 1.07 0.0474 0.299 0.00134 Thyroid gland 0.0427 0.0252 0.000880 0.646 0.0409 0.429 2.22 0.00214 0.101 0.00271 Trachea 0.0819 0.0254 0.000538 1.03 0.0430 0.889 2.57 0.0227 0.301 0.00180 Uterus 0.0652 0.0133 0.000327 0.747 0.0136 0.500 1.96 0.000180 0.0310 0.000970

Table 4. (continued)

Tissue SLC25A10 SLC25A11 SLC25A12 SLC25A13 SLC25A14 SLC25A15 SLC25A16 SLC25A17 SLC25A18 SLC25A19

Adrenal gland 0.00141 0.193 0.0223 0.0331 0.0149 0.00283 0.0462 0.0314 0.00158 0.0295 Bladder BLQ 0.107 0.0502 0.0243 0.00800 0.0119 0.0723 0.0114 0.000877 0.00923 Bone marrow 0.000970 0.233 0.0372 0.0211 0.0164 0.0105 0.0981 0.0128 0.0196 0.00680 Brain 0.000384 0.311 0.0825 0.0146 0.0169 0.00285 0.162 0.0161 0.0433 0.00747 Colon 0.00247 0.297 0.0248 0.0276 0.00420 0.00391 0.0802 0.00648 0.000642 0.0130 Heart 0.00101 1.23 0.438 0.0275 0.0149 0.0130 0.126 0.0120 0.00362 0.0188 Kidney 0.0253 0.730 0.0270 0.0991 0.0104 0.00907 0.160 0.0260 0.00129 0.00907 Liver 0.00832 0.255 0.00335 0.221 0.00494 0.0967 0.0848 0.0212 0.0487 0.00208 Lung 0.000323 0.236 0.0209 0.0236 0.0109 0.00271 0.111 0.00907 0.000565 0.0174 Mammary gland BLQ 0.0191 0.0237 0.0216 0.000710 0.0165 0.139 0.00425 0.00174 0.00685 Ovary BLQ 0.133 0.0224 0.0405 0.00996 0.00907 0.118 0.0489 0.00197 0.00323 Pancreas 0.00289 0.177 0.0148 0.0309 0.0116 0.0243 0.175 0.0258 0.000730 0.0103 Peripheral leukocytes BLQ 0.0957 0.0194 0.0219 0.00576 0.00773 0.0811 0.0128 0.00103 0.00554 Placenta BLQ 0.0280 0.0130 0.0575 0.00760 0.00792 0.200 0.0470 0.00190 0.00803 Prostate 0.00150 0.278 0.0487 0.0527 0.0156 0.00570 0.318 0.0320 0.00580 0.0121 Retina 0.00167 0.280 0.0424 0.0550 0.0125 0.0159 0.179 0.0360 0.00452 0.00945 Salivary gland 0.00261 0.314 0.0527 0.0169 0.0119 0.0120 0.177 0.0227 0.000853 0.0156 Skeletal muscle 0.00377 7.94 1.54 0.0418 0.0264 0.0600 0.323 0.0203 0.0151 0.107 Small intestine 0.00252 0.236 0.0183 0.0517 0.00582 0.0443 0.0925 0.0128 0.000361 0.00779 Smooth muscle BLQ 0.233 0.0713 0.0154 0.00832 0.00739 0.227 0.0116 0.000868 0.0308 Spinal cord 0.00110 0.225 0.0372 0.0581 0.0148 0.00441 0.104 0.0223 0.0780 0.00711 Spleen 0.000542 0.252 0.0163 0.0186 0.00760 0.00335 0.0484 0.0105 0.00168 0.0202 Stomach 0.00328 0.230 0.0247 0.0445 0.00592 0.00719 0.0830 0.0216 0.000468 0.0212 Testis 0.00486 0.127 0.0274 0.0569 0.0433 0.0502 0.0788 0.0696 0.0109 0.262 Thymus 0.000171 0.227 0.0152 0.00657 0.00380 0.00505 0.0638 0.0123 0.000700 0.00626 Thyroid gland 0.00145 0.248 0.0433 0.0467 0.0172 0.0480 0.0981 0.0212 0.000378 0.0107 Trachea 0.00380 0.281 0.0266 0.0364 0.0155 0.00372 0.115 0.0166 0.00127 0.0136 Uterus 0.000129 0.193 0.0229 0.0212 0.0109 0.00666 0.0909 0.0313 0.00118 0.00975

Table 4. (continued)

Tissue SLC25A20 SLC25A21 SLC25A22 SLC25A23 SLC25A24 SLC25A25 SLC25A26 SLC25A27 SLC25A28 SLC25A29

Adrenal gland 0.0185 0.000997 0.0191 0.276 0.223 0.0565 0.167 0.0163 0.0589 0.0830 Bladder 0.0149 0.00151 0.00607 1.54 0.660 0.0501 0.306 0.120 0.176 0.0289 Bone marrow 0.0276 0.0154 0.0504 0.0218 0.312 0.0294 0.119 0.00151 0.0575 0.0213 Brain 0.00479 0.000286 0.0954 1.26 0.0682 0.0627 0.318 0.0756 0.0602 0.0387 Colon 0.00739 0.000698 0.00834 0.540 0.438 0.0186 0.157 0.0263 0.0504 0.0172 Heart 0.0998 0.00309 0.00491 1.24 0.425 0.0124 0.391 0.0682 0.0805 0.0387 Kidney 0.0256 0.00319 0.0165 0.714 0.234 0.0535 0.198 0.0301 0.0434 0.0427 Liver 0.102 0.000307 0.0458 0.182 0.0294 0.0860 0.166 0.0208 0.0393 0.0211 Lung 0.0156 0.000880 0.0145 0.253 0.700 0.0811 0.168 0.0307 0.0479 0.0393 Mammary gland BLQ 0.0000741 0.00280 BLQ 0.371 0.0385 0.150 0.0356 0.195 0.0178 Ovary 0.00453 0.00214 0.00982 0.402 0.367 0.0977 0.275 0.182 0.121 0.0259 Pancreas 0.0126 0.00648 0.158 0.273 0.207 0.151 0.280 0.0303 0.0851 0.0409 Peripheral leukocytes 0.0248 0.0000100 0.0152 0.0951 0.318 0.0408 0.198 0.00121 0.104 0.0537 Placenta 0.00982 0.000411 0.0166 0.0421 0.543 0.0733 0.382 0.0107 0.124 0.0178 Prostate 0.0194 0.00340 0.0145 0.676 0.434 0.0857 0.237 0.135 0.0857 0.0621 Retina 0.0151 0.00191 0.0235 0.519 0.302 0.113 0.352 0.249 0.188 0.0733 Salivary gland 0.0188 0.000987 0.0325 0.779 0.145 0.0352 0.295 0.0190 0.0567 0.197 Skeletal muscle 0.151 0.00238 0.00387 4.41 0.853 0.973 1.52 0.143 0.233 0.106 Small intestine 0.00158 0.00106 0.0213 0.336 0.519 0.0192 0.141 0.0119 0.0368 0.0155 Smooth muscle 0.0157 0.00198 0.00402 1.58 0.503 0.0621 0.412 0.225 0.283 0.0282 Spinal cord 0.00800 0.00108 0.0114 0.644 0.118 0.0557 0.263 0.0389 0.0535 0.0884 Spleen 0.0229 0.000431 0.0134 0.139 0.441 0.0484 0.207 0.00304 0.0436 0.0176 Stomach 0.0195 0.000970 0.0154 0.415 0.344 0.0157 0.147 0.0208 0.0385 0.00142 Testis 0.0271 0.0374 0.0436 0.271 0.413 0.0663 0.576 0.0542 0.322 0.0728 Thymus 0.0149 0.000378 0.0147 0.0530 0.0915 0.0256 0.102 0.00309 0.0477 0.0188 Thyroid gland 0.00996 0.00251 0.00962 1.01 0.308 0.0533 0.330 0.0684 0.0451 0.349 Trachea 0.0173 0.00147 0.0194 0.514 0.337 0.150 0.233 0.0430 0.130 0.138 Uterus 0.00617 0.00172 0.0125 0.435 0.321 0.102 0.187 0.0458 0.0501 0.0364

Table 4. (continued)

Tissue SLC25A30 SLC25A31 SLC25A32 SLC25A33 SLC25A34 SLC25A35 SLC25A36 SLC25A37 SLC25A38 SLC25A39

Adrenal gland 0.0977 0.0000919 0.0322 0.0331 0.00657 0.000263 0.0544 0.874 0.0597 0.221 Bladder 0.148 0.000595 0.0458 0.0941 0.00121 0.000263 0.0783 0.514 0.0748 0.0703 Bone marrow 0.0629 0.0000175 0.0454 0.0302 0.00186 0.000735 0.0412 15.5 0.0703 1.34 Brain 0.0417 0.000135 0.0437 0.132 0.00494 0.0000663 0.0723 0.220 0.0391 0.0706 Colon 0.0427 0.0000254 0.0284 0.0448 0.00466 0.000281 0.0414 0.289 0.0769 0.225 Heart 1.55 0.0000773 0.101 0.136 0.0296 0.0000726 0.255 0.700 0.0517 0.169 Kidney 0.468 0.0000139 0.0350 0.110 0.0148 0.000296 0.0909 0.413 0.0762 0.431 Liver 0.133 BLQ 0.0390 0.0802 0.00648 0.0000517 0.00588 0.118 0.0563 0.184 Lung 0.125 BLQ 0.0472 0.0271 0.000977 0.000348 0.0954 0.874 0.0593 0.130 Mammary gland 0.156 0.0000978 0.0205 0.0884 0.000353 0.00148 0.0359 1.65 0.172 0.841 Ovary 0.247 0.0000535 0.0459 0.0593 0.00177 0.000160 0.0665 0.700 0.103 0.0762 Pancreas 0.0762 0.0000268 0.0297 0.0677 0.00206 0.0000569 0.141 0.367 0.109 0.275 Peripheral leukocytes 0.147 BLQ 0.0431 0.0456 0.00280 0.000419 0.0361 4.27 0.0466 0.119 Placenta 0.102 BLQ 0.0860 0.0280 0.00584 0.00168 0.0934 0.642 0.0634 0.319 Prostate 0.239 0.0000213 0.0899 0.156 0.00107 0.000329 0.151 1.65 0.102 0.208 Retina 0.215 0.0000778 0.0520 0.329 0.00471 0.000416 0.113 0.383 0.105 0.193 Salivary gland 0.0974 BLQ 0.0276 0.144 0.00517 0.000216 0.0506 0.655 0.0494 0.253 Skeletal muscle 4.20 0.000149 0.174 0.747 0.128 0.000235 0.324 2.31 0.476 0.812 Small intestine 0.0389 0.0000107 0.0289 0.0479 0.0123 0.000326 0.0397 0.320 0.0316 0.225 Smooth muscle 0.216 0.0000496 0.0954 0.134 0.00147 0.000169 0.0866 0.497 0.0961 0.0718 Spinal cord 0.0869 0.0000450 0.0447 0.292 0.00113 0.000208 0.0723 0.347 0.0283 0.104 Spleen 0.203 0.0000142 0.0629 0.0508 0.000821 0.000136 0.0728 0.532 0.0454 0.145 Stomach 0.0679 0.0000378 0.0497 0.0689 0.000761 0.000220 0.0526 0.633 0.0374 0.279 Testis 0.181 0.420 0.127 1.17 0.00251 0.0103 0.199 1.54 0.0893 0.452 Thymus 0.0390 0.0000170 0.0278 0.0243 0.000892 0.000341 0.0252 0.147 0.0563 0.0896 Thyroid gland 0.0748 0.000106 0.0480 0.103 0.00168 0.000112 0.117 0.490 0.0866 0.270 Trachea 0.129 0.0000200 0.0454 0.113 0.00115 0.000499 0.0819 1.25 0.0698 0.200 Uterus 0.100 0.0000301 0.0361 0.0352 0.00153 0.000577 0.0878 0.444 0.0556 0.121

Table 4. (continued)

Tissue SLC25A40 SLC25A41 SLC25A42 SLC25A43 SLC25A44 SLC25A45 SLC25A46 SLC26A1 SLC26A2 SLC26A3

Adrenal gland 0.00852 0.000956 0.00570 0.00328 0.322 0.00169 0.0189 0.0221 0.0816 0.0000068 Bladder 0.00685 0.00238 0.0206 0.00979 0.566 0.00269 0.0515 0.00138 0.00282 0.000106 Bone marrow 0.0647 0.00422 0.0111 0.00512 0.511 0.00256 0.0470 0.00272 0.0107 0.0000120 Brain 0.0109 0.0110 0.00737 0.00396 0.553 0.00138 0.0222 0.00814 0.00384 BLQ Colon 0.0128 0.000387 0.00131 0.0112 0.337 0.00161 0.0319 0.00420 0.257 0.307 Heart 0.0145 0.00246 0.0135 0.00755 0.446 0.00493 0.116 0.00214 0.00483 0.0000281 Kidney 0.0119 0.00131 0.0711 0.00760 1.05 0.00574 0.0420 0.0638 0.00270 0.000197 Liver 0.00541 0.00152 0.0540 0.0123 0.660 0.00584 0.0209 0.0292 0.000658 0.0000103 Lung 0.0155 0.000686 0.00659 0.0140 0.380 0.00496 0.0320 0.00359 0.0167 BLQ Mammary gland BLQ 0.000367 BLQ 0.00122 0.722 0.102 0.0738 0.00175 BLQ 0.000649 Ovary 0.0309 0.000892 0.00602 0.00929 0.253 0.00489 0.0225 0.00252 0.00479 0.0000193 Pancreas 0.0205 0.000577 0.00795 0.00755 0.194 0.0636 0.0414 0.00317 0.00795 BLQ Peripheral leukocytes 0.0196 0.000226 0.0126 0.00530 0.850 0.00939 0.0208 0.00481 0.0128 BLQ Placenta 0.0135 0.000106 0.00501 0.0102 0.611 0.00505 0.0526 0.000930 0.0780 0.0000066 Prostate 0.0253 0.00148 0.0190 0.0103 0.434 0.00752 0.0565 0.00427 0.0573 0.0382 Retina 0.00582 0.00416 0.0153 0.00910 0.735 0.00358 0.0751 0.00354 0.00590 0.0000566 Salivary gland 0.00923 0.00175 0.0191 0.0134 0.222 0.00820 0.0250 0.00438 0.0187 0.0000300 Skeletal muscle 0.0387 0.00287 0.126 0.00483 1.68 0.0130 0.507 0.00271 0.00916 0.000153 Small intestine 0.00846 0.000404 0.00711 0.00726 0.338 0.00673 0.0226 0.00834 0.00624 0.0479 Smooth muscle 0.00709 0.00461 0.0176 0.00814 0.334 0.00333 0.129 0.00133 0.00229 0.000225 Spinal cord 0.0154 0.00300 0.0129 0.00576 0.419 0.00183 0.0492 0.00545 0.0334 BLQ Spleen 0.0256 0.000282 0.0125 0.00643 0.448 0.00996 0.0404 0.00338 0.0106 BLQ Stomach 0.0115 0.000911 0.00584 0.0107 0.371 0.00354 0.0458 0.00296 0.00699 0.00904 Testis 0.0453 0.0407 0.0121 0.00685 0.681 0.00450 0.0610 0.00584 0.0207 0.00208 Thymus 0.00989 0.000391 0.00302 0.00340 0.314 0.00568 0.00820 0.00311 0.00370 0.0000343 Thyroid gland 0.0156 0.00150 0.0278 0.00481 0.308 0.00508 0.0436 0.00359 0.0129 0.0000615 Trachea 0.0278 0.00121 0.0164 0.00855 0.518 0.00626 0.0202 0.00362 0.0928 BLQ Uterus 0.00425 0.00161 0.00904 0.0120 0.192 0.00220 0.0235 0.00370 0.00552 0.000499

Table 4. (continued)

Tissue SLC26A4 SLC26A5 SLC26A6 SLC26A7 SLC26A8 SLC26A9 SLC26A10 SLC26A11 SLC27A1 SLC27A2

Adrenal gland 0.000296 0.000241 0.0126 0.000130 0.000286 BLQ 0.00169 0.138 0.232 0.0184 Bladder 0.000688 0.00121 0.00707 0.000346 0.00285 0.000148 0.0178 0.0320 0.0805 0.0148 Bone marrow 0.00122 0.000322 0.0261 0.000242 0.0430 0.0000554 0.00564 0.0100 0.0213 0.0272 Brain 0.00231 0.000456 0.00534 0.000101 0.00765 0.000253 0.0119 0.0342 0.184 0.00473 Colon 0.000464 0.0000808 0.0443 0.000409 0.00356 0.0000324 0.00907 0.0189 0.0462 0.0418 Heart 0.00198 0.000104 0.0105 0.00286 0.000158 0.000301 0.0176 0.0175 0.261 BLQ Kidney 0.00304 0.000139 0.0342 0.0139 0.00151 0.000167 0.00126 0.0575 0.0349 0.956 Liver 0.000167 0.000357 0.00657 0.000138 0.000147 BLQ 0.000223 0.0321 0.0436 0.415 Lung 0.00340 0.000735 0.00949 0.000573 0.00215 0.0364 0.00315 0.0421 0.0884 0.0190 Mammary gland 0.000186 BLQ 0.00916 0.000189 0.00399 0.00164 0.0121 0.0848 0.135 0.0206 Ovary 0.000440 0.0000469 0.0147 0.0000789 0.00185 0.000158 0.00671 0.0878 0.262 BLQ Pancreas 0.000214 0.0000778 0.00996 0.000157 0.00416 0.000715 0.00110 0.0401 0.0708 0.0353 Peripheral leukocytes 0.000194 0.0000243 0.0140 0.000117 0.0274 0.0000062 0.0000190 0.0501 0.0754 0.00521 Placenta 0.00115 BLQ 0.0243 0.0286 0.00254 0.0000726 0.00124 0.156 0.0764 0.0698 Prostate 0.0155 0.00393 0.0160 0.000499 0.00246 0.000298 0.0144 0.0656 0.154 0.0368 Retina 0.0120 0.000273 0.0109 0.0191 0.00169 0.000316 0.0131 0.0845 0.157 0.0725 Salivary gland 0.00167 0.000238 0.00952 0.000896 0.00158 0.553 0.00233 0.0373 0.237 BLQ Skeletal muscle 0.00143 0.0000501 0.0428 0.00115 BLQ 0.000289 0.0140 0.0677 0.530 BLQ Small intestine 0.000283 0.0000533 0.0132 0.000113 0.00104 0.000342 0.00206 0.0204 0.0311 0.0527 Smooth muscle 0.000437 0.000399 0.00923 0.000357 0.00118 0.000157 0.0250 0.0333 0.0902 0.00465 Spinal cord 0.000360 0.000963 0.00630 0.00296 0.00236 0.000322 0.00385 0.0319 0.238 0.00169 Spleen 0.000740 0.000210 0.00949 0.000341 0.00212 BLQ 0.00118 0.0401 0.0693 BLQ Stomach 0.000658 0.000868 0.00955 0.00106 0.00261 0.0748 0.00377 0.0216 0.0583 0.00814 Testis 0.00680 0.00149 0.0138 0.00218 0.493 0.000239 0.00755 0.0461 0.227 0.0102 Thymus 0.000434 0.0000394 0.00861 0.000155 0.000766 0.000239 0.000375 0.0118 0.0310 0.000402 Thyroid gland 1.01 0.00145 0.00584 1.23 0.00282 0.0126 0.00125 0.0652 0.128 0.00904 Trachea 0.00372 0.00111 0.0106 0.00114 0.00584 0.0170 0.00452 0.0451 0.170 0.0836 Uterus 0.00132 0.0000645 0.0112 0.00260 0.00103 0.000217 0.0198 0.0470 0.102 0.000963

Table 4. (continued)

Tissue SLC27A3 SLC27A4 SLC27A5 SLC27A6 SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6

Adrenal gland 0.0287 0.0445 0.0000696 0.0310 0.367 0.000499 0.00564 0.0682 0.0998 0.307 Bladder 0.104 0.0346 0.0000342 0.00358 0.266 0.000144 0.000457 0.120 0.126 0.480 Bone marrow 0.0407 0.0559 0.0000628 0.000258 0.279 0.0000082 0.000103 0.0319 0.171 0.540 Brain 0.00932 0.110 0.000151 0.00272 0.134 BLQ 0.0470 0.156 0.106 0.262 Colon 0.0349 0.0557 0.000168 0.00227 0.172 0.0000596 0.000114 0.0848 0.112 0.337 Heart 0.0365 0.0625 0.00306 0.274 0.462 0.00184 0.0302 0.134 0.267 0.613 Kidney 0.0217 0.0743 1.33 0.000155 0.396 0.00837 0.000143 0.200 0.138 0.527 Liver 0.0693 0.0994 0.0000325 0.0000257 0.387 0.0000341 0.0000912 0.0364 0.100 0.323 Lung 0.0799 0.0252 0.00143 0.00488 0.269 0.0000127 0.000205 0.166 0.239 0.343 Mammary gland 0.253 0.0379 0.0000517 0.00105 0.551 0.000144 0.000761 0.0515 0.371 0.321 Ovary 0.0502 0.0201 0.000168 0.0382 0.229 BLQ 0.000460 0.122 0.149 0.782 Pancreas 0.0213 0.0474 0.0000562 0.000213 0.375 0.0647 0.0000414 0.0355 0.114 0.399 Peripheral leukocytes 0.0577 0.0310 0.0000773 0.0000444 0.239 BLQ 0.0000355 0.0783 0.159 0.576 Placenta 0.0759 0.0764 0.000140 0.0656 0.642 0.0401 0.0000691 0.187 0.470 1.25 Prostate 0.0772 0.0445 0.0000466 0.00776 0.292 0.0000585 0.000977 5.45 0.419 0.657 Retina 0.0376 0.0396 0.0000241 0.00823 0.378 0.000963 0.00444 0.136 0.262 0.613 Salivary gland 0.0134 0.0585 0.000199 0.00196 0.198 0.000625 0.0000775 0.0448 0.149 0.314 Skeletal muscle 0.0583 0.143 0.00230 0.00582 0.321 0.00124 0.000547 0.259 0.358 2.23 Small intestine 0.0264 0.164 0.0000359 0.00195 0.357 0.000232 0.000216 0.271 0.108 0.355 Smooth muscle 0.0689 0.0304 0.0000706 0.000868 0.224 0.000109 0.000180 0.153 0.264 0.722 Spinal cord 0.00817 0.0759 BLQ 0.0454 0.225 0.0000075 0.00404 0.168 0.110 0.350 Spleen 0.0401 0.0206 0.0000378 0.000336 0.406 0.0000316 0.000144 0.184 0.158 0.503 Stomach 0.0511 0.0409 0.00124 0.00229 0.204 0.0000111 0.0000822 0.0934 0.243 0.483 Testis 0.175 0.199 0.0000403 0.0836 1.20 0.000253 0.176 1.27 0.475 1.36 Thymus 0.0209 0.0229 0.0000281 0.0100 0.0791 0.0000077 0.000141 0.0385 0.0890 0.289 Thyroid gland 0.0203 0.0563 0.0000531 0.00227 0.409 0.00244 0.000353 0.247 0.432 0.599 Trachea 0.0591 0.0286 0.000294 0.00975 0.213 0.0000566 0.000109 0.0830 0.188 0.480 Uterus 0.0490 0.0352 BLQ 0.00792 0.247 0.000943 0.000695 0.100 0.141 0.323

Table 4. (continued)

Tissue SLC30A7 SLC30A8 SLC30A9 SLC30A10 SLC31A1 SLC31A2 SLC32A1 SLC33A1 SLC34A1 SLC34A2

Adrenal gland 0.114 0.0000822 0.0649 0.000475 0.148 0.00641 0.0000137 0.154 0.0000320 0.0000566 Bladder 0.0497 0.000555 0.105 0.0000105 0.0698 BLQ 0.0000133 0.0848 0.0000427 0.0000718 Bone marrow 0.149 0.0000295 0.0612 0.000862 0.0825 0.00694 BLQ 0.168 0.000880 0.000103 Brain 0.0269 0.0000590 0.137 0.00211 0.0482 0.0178 0.0223 0.0839 BLQ 0.0000800 Colon 0.0896 0.000178 0.0467 0.00252 0.0825 0.000320 0.0000643 0.0947 0.0000349 0.000158 Heart 0.0619 BLQ 0.557 0.000123 0.115 0.00959 0.0000463 0.239 0.0000373 0.00119 Kidney 0.110 0.00849 0.184 BLQ 0.265 0.00846 0.0000035 0.167 1.20 0.0179 Liver 0.0994 0.0000047 0.0270 0.0684 0.395 0.00572 BLQ 0.123 0.00302 0.00545 Lung 0.260 0.000137 0.124 BLQ 0.148 0.0196 0.0000132 0.146 0.000217 1.82 Mammary gland 0.135 BLQ 0.00969 BLQ 0.00588 0.00326 0.000402 0.0178 BLQ 0.0511 Ovary 0.0672 0.0000466 0.114 0.000465 0.0746 0.00562 0.0000108 0.139 BLQ 0.000761 Pancreas 0.127 0.0587 0.188 0.000419 0.171 0.0176 BLQ 0.151 BLQ 0.0114 Peripheral leukocytes 0.113 0.0000155 0.0550 BLQ 0.0751 0.0322 0.0000236 0.239 0.000336 BLQ Placenta 0.586 0.00326 0.114 BLQ 0.154 0.0529 BLQ 0.299 0.0000528 0.0171 Prostate 0.333 0.000139 0.239 0.0000332 0.365 0.00183 0.0000065 0.271 0.000205 0.00694 Retina 0.0585 0.00157 0.138 0.00149 0.145 0.00846 0.00323 0.170 0.000132 0.0209 Salivary gland 0.140 0.0000630 0.0941 BLQ 0.871 0.189 0.0000081 0.206 0.0000819 0.121 Skeletal muscle 0.101 BLQ 0.702 0.0000108 0.174 0.0166 0.0000095 0.237 0.000281 0.000141 Small intestine 0.132 0.000847 0.0658 0.00460 0.217 0.00316 0.0000083 0.139 0.000172 0.0573 Smooth muscle 0.0679 0.00115 0.163 BLQ 0.0442 0.00468 BLQ 0.132 BLQ 0.0000293 Spinal cord 0.0431 0.000106 0.163 0.00223 0.0845 0.0358 0.00744 0.104 BLQ 0.000115 Spleen 0.170 0.000152 0.0813 BLQ 0.0733 0.0164 BLQ 0.106 0.000375 0.000234 Stomach 0.277 0.000320 0.134 0.000241 0.132 0.00258 0.0000052 0.188 0.0000503 0.00458 Testis 0.141 0.00584 0.290 0.00115 0.215 0.0411 0.00195 0.226 0.000311 0.0252 Thymus 0.120 0.0000189 0.0223 0.0000041 0.0276 0.00512 0.0000610 0.0994 0.0000520 0.00481 Thyroid gland 0.143 0.000176 0.262 0.0000183 0.144 0.0130 BLQ 0.243 0.0000047 0.0242 Trachea 0.232 0.000434 0.0652 BLQ 0.435 0.00955 0.0000230 0.243 0.000139 0.283 Uterus 0.103 0.000167 0.0315 0.0000476 0.0494 0.00258 BLQ 0.145 0.000244 0.0842

Table 4. (continued)

Tissue SLC34A3 SLC37A1 SLC37A2 SLC37A3 SLC37A4 SLC39A1 SLC39A2 SLC39A3 SLC39A4 SLC39A5

Adrenal gland 0.000248 0.0179 0.182 0.0863 0.0147 0.0693 BLQ 0.0725 0.000161 0.00158 Bladder 0.000310 0.0150 0.0159 0.145 0.00678 0.0400 BLQ 0.0454 0.000994 BLQ Bone marrow 0.00132 0.0300 0.00916 0.167 0.0387 0.0201 BLQ 0.180 0.00468 0.00294 Brain 0.00184 0.0140 0.00126 0.103 0.00982 0.0163 BLQ 0.0696 0.00776 BLQ Colon 0.000722 0.0208 0.0192 0.113 0.0246 0.0378 0.00219 0.0356 0.0320 0.737 Heart 0.000520 0.0166 0.00354 0.117 0.0101 0.0567 BLQ 0.0971 BLQ 0.00163 Kidney 0.0608 0.0136 0.00124 0.136 0.171 0.0501 BLQ 0.0649 0.116 2.94 Liver 0.0000834 0.00760 0.0129 0.0302 0.151 0.0372 BLQ 0.0830 0.00185 1.39 Lung 0.00108 0.0437 0.0156 0.120 0.0112 0.0670 BLQ 0.0453 0.0134 0.00140 Mammary gland 0.0000112 0.225 0.00298 0.674 0.00212 BLQ BLQ 0.493 0.00260 BLQ Ovary 0.000705 0.0180 0.00201 0.132 0.0141 0.0679 BLQ 0.0346 0.0175 BLQ Pancreas 0.000437 0.0173 0.000804 0.108 0.0689 0.0464 BLQ 0.0295 0.00111 2.06 Peripheral leukocytes 0.00136 0.0383 0.0208 0.134 0.00709 0.0308 BLQ 0.0425 0.000705 BLQ Placenta 0.000610 0.0533 0.0202 0.247 0.0229 0.227 BLQ 0.0884 0.00519 BLQ Prostate 0.00122 0.0767 0.00675 0.247 0.0319 0.0836 0.0234 0.137 0.00439 BLQ Retina 0.00116 0.0251 0.00613 0.143 0.0168 0.0327 0.0000696 0.0614 0.000950 0.0186 Salivary gland 0.00109 0.0155 0.236 0.222 0.0176 0.0469 0.00121 0.0941 0.000418 BLQ Skeletal muscle 0.000607 0.0324 0.0506 0.255 0.271 0.162 BLQ 0.277 BLQ BLQ Small intestine 0.00156 0.0554 0.00985 0.0799 0.0440 0.0262 BLQ 0.0489 0.115 1.09 Smooth muscle 0.000649 0.0226 0.00545 0.310 0.00576 0.0448 BLQ 0.0304 0.00155 0.00388 Spinal cord 0.00247 0.0172 0.00798 0.0627 0.00873 0.0321 BLQ 0.0538 0.000492 BLQ Spleen 0.000437 0.0202 0.0629 0.0791 0.00910 0.0436 BLQ 0.0638 0.000610 0.00345 Stomach 0.000237 0.0703 0.00714 0.144 0.0102 0.0387 BLQ 0.0775 0.0106 0.0268 Testis 0.00393 0.0746 0.00770 0.138 0.0308 0.0470 BLQ 0.997 0.0135 0.00678 Thymus 0.000573 0.0185 0.00657 0.0830 0.00820 0.0223 0.000357 0.0308 0.000434 0.000569 Thyroid gland 0.000740 0.0367 0.00458 0.195 0.0181 0.0693 BLQ 0.0698 0.0209 0.000880 Trachea 0.00190 0.0583 0.0387 0.210 0.0178 0.0595 BLQ 0.0612 0.00226 BLQ Uterus 0.000561 0.0132 0.00515 0.325 0.0102 0.0575 BLQ 0.103 0.00347 0.000691

Table 4. (continued)

Tissue SLC39A6 SLC39A7 SLC39A8 SLC39A9 SLC39A10 SLC39A11 SLC39A12 SLC39A13 SLC39A14 SLC40A1

Adrenal gland 0.159 0.221 0.00823 0.502 0.205 0.0168 0.000104 0.0893 0.0000329 1.85 Bladder 0.248 0.0994 0.0994 0.493 0.356 0.0216 0.000119 0.0290 BLQ 0.877 Bone marrow 0.0689 0.0713 0.140 0.323 0.155 0.110 0.00929 0.0245 0.0000042 2.75 Brain 0.208 0.0391 0.0271 0.370 1.16 0.0311 0.0313 0.0573 BLQ 0.0610 Colon 0.0819 0.142 0.0808 0.497 0.0703 0.0458 0.000135 0.0583 0.00624 0.511 Heart 0.225 0.170 0.0725 0.372 0.459 0.0129 0.000298 0.171 0.0000030 1.98 Kidney 0.145 0.180 0.0672 0.593 0.225 0.0394 0.0000602 0.198 0.00879 0.956 Liver 0.0748 0.215 0.0872 0.683 0.0448 0.0315 0.0000958 0.0354 0.0866 2.16 Lung 0.329 0.150 0.930 0.428 0.443 0.0350 0.000167 0.128 0.000210 2.27 Mammary gland 0.403 0.153 0.0211 0.418 0.420 0.00843 0.0000253 0.0909 BLQ 0.847 Ovary 0.267 0.0816 0.115 0.326 0.309 0.0126 0.0000236 0.0822 0.0000091 2.31 Pancreas 0.386 0.357 0.498 0.943 0.157 0.0450 BLQ 0.105 0.0223 1.11 Peripheral leukocytes 0.175 0.0649 0.0431 0.331 0.498 0.0334 BLQ 0.0654 BLQ 0.648 Placenta 1.21 0.908 1.17 1.60 0.374 0.0288 0.000577 0.306 0.0000450 4.32 Prostate 2.80 0.471 0.0991 1.12 3.45 0.0443 0.0000279 0.118 0.00116 0.990 Retina 0.462 0.117 0.129 0.498 0.402 0.0248 0.310 0.0845 0.0000101 0.549 Salivary gland 0.235 0.480 0.486 1.88 0.0689 0.0698 BLQ 0.108 0.000448 0.435 Skeletal muscle 0.346 0.272 0.0445 0.801 0.490 0.00393 BLQ 0.356 BLQ 6.11 Small intestine 0.0645 0.249 0.0456 0.576 0.106 0.0417 0.0000617 0.117 0.0127 1.63 Smooth muscle 0.270 0.0954 0.0748 0.312 0.412 0.00439 0.000116 0.110 0.0000074 0.829 Spinal cord 0.431 0.0772 0.0686 0.502 0.868 0.0495 0.0238 0.0839 0.0000049 0.313 Spleen 0.127 0.0819 0.0754 0.483 1.22 0.0208 0.000211 0.0718 0.0000214 6.32 Stomach 0.202 0.406 0.0638 0.532 0.293 0.0656 0.0000299 0.0941 0.00749 1.17 Testis 0.639 0.160 0.0440 0.856 2.18 0.0422 0.00115 0.549 0.0000531 0.755 Thymus 0.0902 0.0522 0.0526 0.252 0.122 0.0100 0.0000153 0.0494 BLQ 0.473 Thyroid gland 0.356 0.199 0.0819 0.660 1.60 0.0490 0.0000539 0.0780 0.0112 1.14 Trachea 0.325 0.332 0.293 0.697 0.210 0.0896 0.000149 0.133 0.000373 1.09 Uterus 0.252 0.188 0.0647 0.486 0.193 0.0224 0.0000420 0.133 0.0000925 1.14

Table 4. (continued) findings of our previous study,9) the expression of PPIA mRNA was 13-fold higher in the thymus and 12-fold higher in the Tissue SLC41A1 SLC41A2 SLC41A3 brainthaninskeletalmuscle(datanotshown). Adrenal gland 0.0333 0.00757 0.0931 The mRNA expression levels of 173 human SLC transport- Bladder 0.0117 0.0122 0.0684 ers in various tissues are shown in Table 4. Similar to the find- Bone marrow 0.0103 0.00172 0.0223 16) 17) Brain 0.0212 0.0112 0.112 ings of other studies in human subjects and in a rat , Colon 0.00332 0.0114 0.0439 SLC8A1 mRNA was expressed ubiquitously and was expressed Heart 0.418 0.00535 0.110 at the highest levels in heart. Similar to the findings of other Kidney 0.0209 0.00747 0.0668 17,18) Liver 0.00204 0.0552 0.0238 studies in a rat, SLC8A2 mRNA was expressed at the Lung 0.0105 0.0101 0.0520 highest levels in brain. Similar to the findings of another study Mammary gland 0.0000116 BLQ BLQ in a rat,17) SLC8A3 mRNA was expressed at the highest levels Ovary 0.0179 0.00939 0.0938 Pancreas 0.0477 0.0198 0.0984 in skeletal muscle. Peripheral leukocytes 0.00820 0.000390 0.0405 SLC9A1 mRNA was expressed ubiquitously and was ex- Placenta 0.00613 0.0748 0.0854 pressed at the highest levels in the salivary gland. SLC9A2 Prostate 0.0328 0.0115 0.0672 Retina 0.0235 0.00711 0.0816 mRNA was found to be widely expressed in all tissues and was Salivary gland 0.00692 0.0296 0.0848 expressed at the highest levels in the stomach. Similar to the Skeletal muscle 0.375 0.00300 0.493 findings of another study in human subjects,19) SLC9A3 mRNA Small intestine 0.00510 0.0142 0.0381 Smooth muscle 0.0150 0.00639 0.0587 was expressed ubiquitously and was expressed at the highest Spinal cord 0.0300 0.0130 0.113 levels in kidney. SLC9A4 mRNA was expressed at high levels in Spleen 0.00885 0.00787 0.0713 the stomach and kidney, with no or very weak expression in Stomach 0.0134 0.0288 0.0497 Testis 0.0754 0.0343 0.505 other tissues. SLC9A5 mRNA was expressed ubiquitously. Thymus 0.00685 0.00261 0.0575 Consistent with the findings of another study in human sub- Thyroid gland 0.0421 0.0280 0.138 jects,20) SL9A6 mRNA was expressed ubiquitously and was ex- Trachea 0.0140 0.0205 0.122 Uterus 0.0143 0.00449 0.104 pressed at the highest levels in the brain and skeletal muscle. Similar to the findings of another study in human subjects,21) BLQ, below the limit of quantification. Data are expressed as the ratio of the target mRNA to PPIA mRNA. Experiments were performed in duplicate. The highest values among the SL9A7 mRNA was expressed ubiquitously and was expressed various tissues are shown in boxes. at the highest levels in the mammary gland and skeletal muscle. mRNA Expression Profiles of Human SLC Transporters 37

Similar to the findings of other studies in human subjects,22,23) other tissues. SLC17A5 mRNA was expressed ubiquitously. SLC9A8 and SLC9A9 mRNA were expressed ubiquitously and Similar to the findings of another study in human subjects,34) were expressed at the highest levels in skeletal muscle and SLC17A6 mRNA was detectable in the brain, heart, pancreas, smooth muscle, respectively. Both SLC9A10 and SLC9A11 retina, spinal cord, and testis. Similar to the findings of another mRNAwereexpressedathighlevelsinthetestis,withnoor study in human subjects,34) SLC17A7 mRNA was detectable in very weak expression in other tissues. the all tissues and was expressed at high levels in the bone mar- Consistent with the findings of another study in human sub- row, brain, and retina. SLC17A8 mRNA was expressed at high jects,24) SLC11A1 mRNA was expressed ubiquitously and was levels in the retina, testis, and thymus, with no or very weak expressed at the highest levels in peripheral leukocytes. expression in other tissues. SLC11A2 mRNA was also expressed ubiquitously, except in SLC18A1 mRNA was expressed at high levels in the adrenal the mammary gland. gland, colon, and small intestine, with no or very weak expres- Both SLC12A1 and SLC12A3 mRNA were expressed at high sion in other tissues. SLC18A2 mRNA was expressed ubiqui- levels in the kidney, with no or very weak expression in other tously and was expressed at the highest levels in the prostate. tissues. The result for SLC12A3 was similar to that reported in SLC18A3 mRNA was expressed at high levels in the colon, human subjects.25) SLC12A2, SLC12A4, SLC12A6, SLC12A7, mammary gland, placenta, retina, small intestine, and spinal SLC12A8, and SLC12A9 mRNA were expressed ubiquitously. cord, with no or very weak expression in other tissues. The results for SLC12A2, SLC12A4, SLC12A6, SLC12A7, and Similar to the findings of another study in human subjects,35) SLC12A9 were similar to those reported in human subjects.2- SLC19A1 mRNA was expressed ubiquitously and was ex- 6–29) SLC12A5 mRNA was expressed at high levels in the bone pressed at the highest levels in peripheral leukocytes, followed marrow, brain, retina, and spinal cord, with no or very weak by the placenta. Similar to the findings of another study in hu- expression in other tissues. man subjects,36) SLC19A2 mRNA was also expressed ubiqui- Consistent with the findings of another study in human sub- tously and was expressed at the highest levels in skeletal mus- jects,30) SLC13A1 mRNA was expressed at high levels in the cle, followed by the placenta and then the heart. Similar to the kidney, with no or very weak expression in other tissues. findings of another study in human subjects,37) SLC19A3 SLC13A2 mRNA was expressed at high levels in the kidney, mRNA was also expressed ubiquitously, except in peripheral salivary gland, small intestine, and trachea. SLC13A3 mRNA leukocytes and the spleen, and was expressed at the highest was expressed at the highest levels in the kidney. Similar to the levels in the placenta. findings of another study in human subjects,31) SLC13A4 SLC20A1 and SLC20A2 mRNA were expressed ubiquitous- mRNA was expressed ubiquitously and was expressed at high ly. levels in the placenta and retina. Similar to the findings of SLC23A1 mRNA was expressed at the highest levels in the another study in human subjects,32) SLC13A5 mRNA was ex- kidney and was expressed at high levels in the colon, liver, pressed at high levels in the liver and salivary gland. lung, pancreas, prostate, salivary gland, small intestine, SLC14A1 mRNA was expressed at high levels in the bone stomach, testis, thymus, and trachea, with no expression in marrow, prostate, and spinal cord. SLC14A2 mRNA was ex- other tissues. SLC23A2 mRNA was expressed ubiquitously. pressed at high levels in the colon, kidney, skeletal muscle, SLC23A3 mRNA was expressed at the highest levels in the kid- small intestine, and testis. ney and was expressed at high levels in other tissues, with no SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, expression in the bladder, brain, heart, pancreas, skeletal mus- SLC16A7, SLC16A8, SLC16A11, SLC16A13, and SLC16A14 cle, testis, and trachea. mRNA were expressed ubiquitously. SLC16A6, SLC16A9, and SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, and SLC16A12 mRNA were also expressed ubiquitously, except in SLC24A6 mRNA were expressed ubiquitously and were ex- smooth muscle, peripheral leukocytes, and peripheral leuko- pressed at the highest levels in the retina, brain, skeletal mus- cytes, respectively. SLC16A10 mRNA was expressed at the cle, spinal cord, retina, and adrenal gland, respectively. highest levels in skeletal muscle and was not detectable in the Three SLC25A mRNAs (SLC25A1, SLC25A13, and bladder, mammary gland, smooth muscle, or uterus. SLC25A15) were expressed ubiquitously and were expressed Similar to the findings of another study in human subjects,33) at the highest levels in the liver. The result for SLC25A13 was SLC17A1 mRNA was expressed at the highest levels in the kid- similar to that reported in human subjects.38) The result for ney and was detectable in the adrenal gland, liver, mammary SLC25A15 was also similar to that reported in human sub- gland, ovary, retina, testis, thymus, and uterus. SLC17A2 jects.39) Thirteen SLC25A mRNAs (SLC25A3, SLC25A8, mRNA was expressed at the highest levels in the liver and was SLC25A9, SLC25A16, SLC25A23, SLC25A24, SLC25A25, detectable in the adrenal gland, kidney, pancreas, and testis. SLC25A26, SLC25A32, SLC25A36, SLC25A37, SLC25A44, SLC17A3 mRNA was expressed at the highest levels in the kid- and SLC25A46) were expressed ubiquitously and at the highest ney and was detectable in the adrenal gland, liver, lung, ovary, levels in skeletal muscle. The results for SLC25A23, peripheral leukocytes, retina, spinal cord, and testis. SLC17A4 SLC25A24, and SLC25A25 were similar to those reported in mRNA was expressed at high levels in the colon, liver, pan- human subjects40) Six SLC25A mRNAs (SLC25A4, SLC25A11, creas, and small intestine, with no or very weak expression in SLC25A12, SLC25A30, and SLC25A34) were expressed ubi- 38 Masuhiro NISHIMURA and Shinsaku NAITO quitously and were expressed at the highest levels in skeletal pressed at the highest levels in skeletal muscle. SLC27A3 and muscle, followed by the heart. The result for SLC25A12 was SLC27A4 mRNA were expressed ubiquitously. Similar to the similar to that reported in human subjects.41) Seventeen findings of another study in human subjects,50) SLC27A6 SLC25A mRNAs (SLC25A5, SLC25A6, SLC25A14, mRNA was expressed ubiquitously and was expressed at the SLC25A17, SLC25A18, SLC25A19, SLC25A21, SLC25A22, highest levels in the heart. SLC27A2 mRNA was expressed at SLC25A27, SLC25A28, SLC25A29, SLC25A33, SLC25A37, the highest levels in the kidney and was expressed at high levels SLC25A39, SLC25A41, SLC25A43, and SLC25A45) were also in other tissues, with no expression in the heart, ovary, salivary expressed ubiquitously. The result for SLC25A14 was similar gland, skeletal muscle, and spleen. SLC27A5 mRNA was ex- to that reported in human subjects.42) The results for pressed at the highest levels in the kidney and was expressed at SLC25A18 and SLC25A22 were similar to those reported in high levels in the heart, lung, skeletal muscle, and stomach, human subjects.43) The result for SLC25A28 was similar to that with no or very weak expression in other tissues. reported in human subjects.44) Similar to the findings of SLC30A1, SLC30A4, SLC30A5, SLC30A6, SLC30A7, and another study in human subjects,45) SLC25A20 mRNA was ex- SLC30A9 mRNA were expressed ubiquitously. SLC30A2 pressed ubiquitously, except in the mammary gland and was mRNA was expressed at high levels in the heart, kidney, pan- expressed at the highest levels in skeletal muscle. Both creas, placenta, skeletal muscle, and thyroid gland, with no or SLC25A40 and SLC25A42 mRNA were expressed ubiquitous- very weak expression in other tissues. SLC30A3 mRNA was ly, except in the mammary gland. SLC25A2 mRNA was ex- expressed at the highest levels in the testis and was expressed pressed at high levels in peripheral leukocytes, the placenta, at high levels in the adrenal gland, brain, heart, retina, and spi- smallintestine,andtestis,withnoorveryweakexpressionin nal cord, with low levels of expression in other tissues. Similar other tissues. SLC25A7 mRNA was expressed at high levels in to the findings of another study in human subjects,51) SLC30A8 the adrenal gland, heart, testis, thymus, thyroid gland, and mRNA was expressed at the highest levels in the pancreas and trachea, with low levels of expression in other tissues. at high levels in the kidney, placenta, retina, smooth muscle, SLC25A10 mRNA was expressed at the highest levels in the and testis, with no or weak expression in other tissues. kidney and was expressed at high levels in other tissues, with SLC30A10mRNAwasexpressedathighlevelsinthebrain, no expression in the bladder, mammary gland, ovary, peripher- colon, liver, retina, small intestine, spinal cord, and testis, with al leukocytes, placenta, and smooth muscle. Similar to the find- no or very weak expression in other tissues. ings of another study in human subjects,46) SLC25A31 mRNA SLC31A1 mRNA was expressed ubiquitously and was ex- wasexpressedathighlevelsinthetestis,withnoorveryweak pressed at the highest levels in the salivary gland. SLC31A2 expression in other tissues. SLC25A35 mRNA was expressed mRNA was also expressed ubiquitously, except in the bladder, at high levels in the mammary gland, placenta, and testis, with and was expressed at the highest levels in the salivary gland. low levels of expression in other tissues. The results for SLC31A1 and SLC31A2 were similar to those Similar to the findings of another study in human subjects,47) reported in human subjects.52) SLC26A1 mRNA was expressed ubiquitously and was ex- Similar to the findings of another study in the rat,53) pressed at high levels in the adrenal gland, kidney, and liver. SLC32A1 mRNA was expressed at the highest levels in the SLC26A6, SLC26A10, and SLC26A11 mRNA were expressed brain and was expressed at high levels in the retina, spinal ubiquitously. SLC26A2 and SLC26A8 mRNA were also ex- cord, and testis, with no or very weak expression in other tis- pressed ubiquitously, except in the mammary gland and sues. skeletal muscle, respectively. SLC26A4 mRNA was expressed Similar to the findings of another study in human subjects,54) ubiquitously, and was expressed at the highest levels in the SLC33A1 mRNA was expressed ubiquitously. thyroid gland. Similar to the findings of another study in hu- Similar to the findings of another study in human subjects,55) man subjects,48) SLC26A7 mRNA was expressed ubiquitously SLC34A1 mRNA was expressed at the highest levels in the kid- and was expressed at the highest levels in the thyroid gland and ney, followed by the liver, with no or very weak expression in at high levels in the kidney, placenta, and retina. SLC26A3 other tissues. Similar to the findings of another study in human mRNA was expressed at the highest levels in the colon and was subjects,56) SLC34A2 mRNA was found to be widely expressed expressed at high levels in the prostate, small intestine, in all tissues except peripheral leukocytes, with the highest lev- stomach, and testis, with no or very weak expression in other el of expression in the lung. SLC34A3 mRNA was expressed tissues. SLC26A5 mRNA was expressed at high levels in the ubiquitously and was expressed at the highest levels in the kid- bladder, prostate, testis, thyroid gland, and trachea, with no or ney. very weak expression in other tissues. SLC26A9 mRNA was SLC37A1, SLC37A2, SLC37A3, and SLC37A4 mRNA were expressed at the highest levels in the salivary gland and was ex- expressed ubiquitously. pressed at high levels in the lung, mammary gland, stomach, Similar to the findings of another study in human subjects,57) thyroid gland, and trachea, with no or very weak expression in SLC39A1 mRNA was expressed ubiquitously, except in the other tissues. mammary gland. SLC39A2 mRNA was expressed at high levels Similar to the findings of another study in human subjects,49) in the colon, prostate, and salivary gland and was detectable in SLC27A1 mRNA was expressed ubiquitously and was ex- the retina and thymus. SLC39A3, SLC39A6, SLC39A7, mRNA Expression Profiles of Human SLC Transporters 39 ) and open  ) and bars indi- which the mean  ) are the same as the data in Table 4. Closed (  obtained from HAB, respectively. Small clos ed circles ( te. The data in this figure shows the SLC transporters for r than 0.001. Closed circles ( 10) for the total RNA obtained from HAB. ＝ of human SLC transporters in the liver chased from CLONTECH Laboratories and the total RNA to PPIA mRNA. Experiments were performed in duplica ividual data (n 10) for the total RNA obtained from HAB were greate ＝ Individual differences in the mRNA expression ) circles are the individual data for the total RNA pur  ( cate the mean and standard deviation of the ind mRNA values of the individual data (n Fig. 1. Data are expressed as the ratio of the target mRNA 40 Masuhiro NISHIMURA and Shinsaku NAITO (continued) Fig. 1

SLC39A8, SLC39A9, SLC39A10, SLC39A11, and SLC39A13 testine, followed by the adrenal gland, bone marrow, heart, mRNA were expressed ubiquitously. SLC39A4 mRNA was lung, retina, smooth muscle, spleen, stomach, and testis, and found to be widely expressed in all tissues, except in the heart was detectable in the thymus, thyroid gland, and uterus. and skeletal muscle, with high levels of expression in both the SLC39A12 mRNA was expressed at the highest levels in the re- kidney and small intestine. Similar to the findings of another tina and was expressed at high levels in the bone marrow, study in human subjects,58) SLC39A5 mRNA was expressed at brain, spinal cord, and testis, with no or very weak expression high levels in the colon, kidney, liver, pancreas, and small in- in other tissues. SLC39A14 mRNA was expressed at high levels mRNA Expression Profiles of Human SLC Transporters 41

Table 5. Reference Lists for Our Measurements of mRNAs of Human Metabolizing Enzymes, Transporters, and Nuclear Receptors Using the TaqMan Method

Abbreviation (Parentheses: Reference Numbers)

Phase I metabolizing enzymes14,59,60) DH1A,ADH1B,ADH1C,ADH4,ADH5,ADH6,ADH7,DHRS2,HADH2,ALDH1A1,ALDH1A2,ALDH1A3,ALDH1B1,ALDH2,ALDH3A1,ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH8A1, ALDH9A1, AOX1, CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A7, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP4A11, CYP4B1, CYP4F2, CYP4F3, CYP4F8, CYP5A1, CYP7B1, CYP8A1, CYP8B1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP24A1, CYP26A1, CYP27A1, CYP27B1, CYP39A1, CYP46A1, CYP51A1, DPYD, EPHX1, EPHX2, AADAC, CEL, CES1, CES2, ESD, GZMA, GZMB, LIPA, NTE, UCHL1, UCHL3, FMO1, FMO2, FMO3, FMO4, FMO5, MAOA, MAOB, PTGS1, PTGS2, NQO1, NQO2, TP53I3, XDH Phase II metabolizing enzymes14,59,62,63) AANAT, NAT1, NAT2, NAT5, BAAT, DDOST, UGT1A1, UGT1A6, UGT1A9, UGT2A1, UGT2B7, UGT2B10, UGT2B15, UGT2B17, UGT8, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTP1, GSTT1, GSTT2, GSTZ1, MGST1, MGST2, MGST3, PTGES, ASMT, COMT, GAMT, HNMT, NNMT, PEMT, PNMT, TPMT, SULT1A1, SULT1A3, SULT1B1, SULT1E1, SULT2A1, SULT2B1, SULT4A1 ABC transporters9,59) ABCA1, ABCA2, ABCA3, ABCA4, ABCA5, ABCA6, ABCA7, ABCA8, ABCA9), ABCA10, ABCA12, ABCB1, ABCB2, ABCB3, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCB10, ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC7, ABCC8, ABCC9, ABCC10, ABCC11, ABCC12, ABCD1, ABCD2, ABCD3, ABCD4, ABCE1, ABCF1, ABCF2, ABCG1, ABCG2, ABCG4, ABCG5, ABCG8 SLC transporters9, present study) SLC1A1, SLC1A2, SLC1A3, SLC1A4, SLC1A5, SLC2A1, SLC2A2, SLC2A3, SLC2A4, SLC2A5, SLC2A7, SLC2A8, SLC2A9, SLC2A10, SLC2A11, SLC2A12, SLC2A13, SLC2A14, SLC3A1, SLC3A2, SLC4A1, SLC4A2, SLC4A3, SLC4A4, SLC4A7, SLC4A8, SLC4A9, SLC4A10, SLC4A11, SLC5A1, SLC5A2, SLC5A3, SLC5A4, SLC5A5, SLC5A6, SLC5A7, SLC5A8, SLC5A10, SLC5A11, SLC5A12, SLC6A2, SLC6A3, SLC6A4, SLC6A5, SLC6A6, SLC6A7, SLC6A9, SLC6A19, SLC7A1, SLC7A2, SLC7A3, SLC7A4, SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A9, SLC7A10, SLC7A11, SLC7A13, SLC8A1, SLC8A2, SLC8A3, SLC9A1, SLC9A2, SLC9A3, SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9A10, SLC9A11,SLC10A1, SLC10A2, SLC10A3, SLC10A4, SLC10A5, SLC11A1, SLC11A2, SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7, SLC12A8, SLC12A9, SLC13A1, SLC13A2, SLC13A3, SLC13A4, SLC13A5, SLC14A1, SLC14A2, SLC15A1, SLC15A2, SLC15A3, SLC15A4, SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14, SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC18A1, SLC18A2, SLC18A3, SLC19A,1 SLC19A2, SLC19A3, SLC20A1, SLC20A2, SLC21A3, SLC21A6, SLC21A9, SLC21A11, SLC21A12, SLC21A14, SLC21A15, SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC23A1, SLC23A2, SLC23A3, SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC24A6, SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, SLC25A7, SLC25A8, SLC25A9, SLC25A10, SLC25A11, SLC25A12, SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A30, SLC25A31, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46, SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A10, SLC26A11, SLC27A1, SLC27A2, SLC27A3, SLC27A4, SLC27A5, SLC27A6, SLC28A1, SLC28A2, SLC28A3, SLC29A1, SLC29A2, SLC29A3, SLC29A4, SLC30A1, SLC30A2, SLC30A3, SLC30A4, SLC30A5, SLC30A6, SLC30A7, SLC30A8, SLC30A9, SLC30A10, SLC31A1, SLC31A2, SLC32A1, SLC33A1, SLC34A1, SLC34A2, SLC34A3, SLC36A1, SLC36A2, SLC36A3, SLC36A4, SLC37A1, SLC37A2, SLC37A3, SLC37A4, SLC38A1, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6, SLC39A1, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A14, SLC40A1, SLC41A1,SLC41A2, SLC41A3 Nuclear receptors12) NR1A1, NR1A2, NR1B1, NR1B2, NR1B3, NR1C1, NR1C2, NR1C3, NR1D1, NR1D2, NR1F1, NR1F2, NR1F3, NR1H2, NR1H3, NR1H4, NR1I1, NR1I2, NR1I3, NR2A1, NR2A2, NR2B1, NR2B2, NR2B3, NR2C1, NR2C2, NR2E1, NR2E3, NR2F1, NR2F2, NR3A1, NR3A2, NR3B1, NR3C1, NR3C2, NR3C3, NR3C4, NR4A1, NR4A2, NR4A3, NR5A1, NR5A2, NR6A1

in the colon, kidney, liver, pancreas, prostate, small intestine, ly lower than those in the total RNA obtained from HAB. stomach, and thyroid gland, with no or very weak expression Therefore, with a few exceptions, it is suggested that the data in other tissues. shown in Table 4 accurately reflects the relative abundance of SLC40A1 mRNA was expressed ubiquitously. mRNAs in the liver and other tissues, although these are based SLC41A1 mRNA was expressed ubiquitously. Both on the results for only one sample. SLC41A2 and SLC41A3 mRNA were also expressed ubiqui- The detection and quantitative analysis of specific RNA tously, except in the mammary gland. molecules is important for monitoring gene expression. We The individual differences in the mRNA expression of hu- have developed an analytic method for quantifying the mRNA man SLC transporters in the liver are shown in Figure 1.The levels of phase I drug-metabolizing enzymes in humans,14,59,60) dispersion of the mRNA levels of each of the SLC transporters the cynomolgus monkey,61) and the rat,15,61) of phase II drug- in the total RNA obtained from HAB differed by factors of metabolizing enzymes in humans,14,59,62,63) of transporters in several times, dozens of times, or more. The mRNA levels of humans9,59, present study) and the rat,64,65) and of nuclear receptors the SLC transporters other than SLC14A1 and SLC27A5 in humans12) and the rat64,66) in various samples such as cul- mRNA in the liver in the total RNA purchased from CLON- tured cells, blood samples, biopsy specimens, and so on. Table TECH Laboratories were the same as, slightly higher, or slight- 5 lists the references for our studies concerning the measure- 42 Masuhiro NISHIMURA and Shinsaku NAITO ment of these human mRNA targets by the TaqMan method. iol., 288: C223–C239 (2005). We have adopted the one-step RT-PCR method to measure the 12) Nishimura, M., Naito, S. and Yokoi, T.: Tissue-specific mRNA expression levels of every target gene related to the gene in- expression profiles of human nuclear receptor subfamilies. Drug duction of drug-metabolizing enzymes in primary cultures of Metab. Pharmacokinet., 19: 135–149 (2004). human hepatocytes59,61,65,67–71) and to the tissue-specific profiles 13) Nishimura, M. and Naito, S.: Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol. of mRNA expression in human tissues, as described in our Pharm. Bull., 28: 886–892 (2005). previous studies9,12–14,60,72) and the present study. 9,12,14,60) 14) Nishimura, M. and Naito, S.: Tissue-specific mRNA expression In conclusion, the results of our previous studies and profiles of human phase I metabolizing enzymes except for the present study provide valuable information concerning the cytochrome P450 and phase II metabolizing enzymes. Drug tissue-specific profiles of mRNA expression of 90 human phase Metab. Pharmacokinet., 21: 357–374 (2006). I metabolizing enzymes, 48 human phase II metabolizing en- 15) Yamaguchi, M., Yamauchi, A., Nishimura, M., Ueda, N. and zymes, 46 human ABC transporters, 281 human SLC trans- Naito, S.: Soybean oil fat emulsion prevents cytochrome P450 porters, and 43 human nuclear receptors. These findings mRNA down-regulation induced by fat-free overdose total should be helpful in studies concerning the regulation of drug- parenteral nutrition in infant rats. Biol. Pharm. Bull., 28: metabolizing enzymes and transporters in drug screening sys- 143–147 (2005). tems for new chemical entities in new drug development, as 16) Komuro, I., Wenninger, K. E., Philipson, K. D. and Izumo, S.: Molecular cloning and characterization of the human cardiac well as in studies concerning the regulation of transport in Na＋/Ca2＋ exchanger cDNA. Proc. Natl. Acad. Sci. USA, 89: research related to the clinical diagnosis of disease. In particu- 4769–4773 (1992). lar, the information obtained in these studies is expected to be 17) Nicoll, D. A., Quednau, B. D., Qui, Z., Xia, Y. R., Lusis, A. J. important in assessing the feasibility of measuring the mRNA and Philipson, K. D.: Cloning of a third mammalian Na＋-Ca2＋ expression levels of target genes in various tissues. exchanger, NCX3. J. Biol. Chem., 271: 24914–24921 (1996). 18) Li, Z., Matsuoka, S., Hryshko, L. V., Nicoll, D. A., Bersohn, M. Acknowledgments: The authors would like to thank David M., Burke, E. P., Lifton, R. P. and Philipson, K. D.: Cloning of G. Spear, M.D., for reviewing this manuscript. theNCX2isoformoftheplasmamembraneNa＋-Ca2＋ exchanger. J. Biol. Chem., 269: 17434–17439 (1994). References 19) Brant,S.R.,Yun,C.H.,Donowitz,M.andTse,C.M.:Cloning, tissue distribution, and functional analysis of the human Na＋/ 1) Kanai, Y. and Endou, H.: Functional properties of multispecific ＋ amino acid transporters and their implications to transporter- N exchanger isoform, NHE3. Am.J.Physiol., 269: C198– mediated toxicity. J. Toxicol. Sci., 28: 1–17 (2003). C206 (1995). 20) Numata, M., Petrecca, K., Lake, N. and Orlowski, J.: Identifica- 2) Nakamura, N., Masuda, S., Takahashi, K., Saito, H., Okuda, M. ＋＋ and Inui, K.: Decreased expression of glucose and peptide trans- tion of a mitochondrial Na /H exchanger. J. Biol. Chem., 273: porters in rat remnant kidney. Drug Metab. Pharmacokinet., 19: 6951–6959 (1998). 21) Numata, M. and Orlowski, J.: Molecular cloning and characteri- 41–47 (2004). ＋＋＋ 3) Tsuji, A.: Transporter-mediated drug interactions. Drug Metab. zation of a novel (Na ,K )/H exchanger localized to the Pharmacokinet., 17: 253–274 (2002). trans-Golgi network. J. Biol. Chem., 276: 17387–17394 (2001). 22) Goyal,S.,VandenHeuvel,G.andAronson,P.S.:Renalexpres- 4) Halestrap, A. P. and Price, N. T.: The proton-linked monocar- ＋＋ boxylate transporter (MCT) family: structure, function and sion of novel Na /H exchanger isoform NHE8. Am. J. Physiol. regulation. Biochem. J., 343 Pt 2: 281–299 (1999). Renal Physiol., 284: F467–F473 (2003). 23) Nakamura, N., Tanaka, S., Teko, Y., Mitsui, K. and Kanazawa, 5) Huang, Y.: Pharmacogenetics/genomics of membrane transport- ＋＋ ers in cancer chemotherapy. Cancer Metastasis Rev., 26: H.: Four Na /H exchanger isoforms are distributed to Golgi 183–201 (2007). and post-Golgi compartments and are involved in organelle pH 6) Liuzzi, J. P. and Cousins, R. J.: Mammalian zinc transporters. regulation. J. Biol. Chem., 280: 1561–1572 (2005). Annu. Rev. Nutr., 24: 151–172 (2004). 24) Cellier, M., Govoni, G., Vidal, S., Kwan, T., Groulx, N., Liu, J., 7) Dawson, P. A. and Markovich, D.: Pathogenetics of the human Sanchez, F., Skamene, E., Schurr, E. and Gros, P.: Human natur- SLC26 transporters. Curr. Med. Chem., 12: 385–396 (2005). al resistance-associated macrophage protein: cDNA cloning, 8) Goytain, A. and Quamme, G. A.: Functional characterization of chromosomal mapping, genomic organization, and tissue-specif- the mouse [corrected] solute carrier, SLC41A2. Biochem. ic expression. J. Exp. Med., 180: 1741–1752 (1994). Biophys. Res. Commun., 330: 701–705 (2005). 25) Chang,H.,Tashiro,K.,Hirai,M.,Ikeda,K.,Kurokawa,K.and 9) Nishimura, M. and Naito, S.: Tissue-specific mRNA expression Fujita, T.: Identification of a cDNA encoding a thiazide-sensitive profiles of human ATP-binding cassette and solute carrier trans- sodium-chloride cotransporter from the human and its mRNA porter superfamilies. Drug Metab. Pharmacokinet., 20: 452–477 expression in various tissues. Biochem. Biophys. Res. Commun., (2005). 223: 324–328 (1996). 10) Palmieri, F.: The mitochondrial transporter family (SLC25): 26) Payne, J. A., Xu, J. C., Haas, M., Lytle, C. Y., Ward, D. and For- physiological and pathological implications. Pflugers Arch., 447: bush, B.: Primary structure, functional expression, and chro- 689–709 (2004). mosomal localization of the bumetanide-sensitive Na-K-Cl 11) Brett, C. L., Donowitz, M. and Rao, R.: Evolutionary origins of cotransporter in human colon. J. Biol. Chem., 270: 17977– eukaryotic sodium/proton exchangers. Am.J.Physiol.,CellPhys- 17985 (1995). mRNA Expression Profiles of Human SLC Transporters 43

27) Gillen, C. M., Brill, S., Payne, J. A. and Forbush, B.: Molecular new member of the mitochondrial carrier superfamily that cloning and functional expression of the K-Cl cotransporter binds calcium and is present in human muscle and brain. J. Biol. from rabbit, rat, and human. A new member of the cation-chlo- Chem., 273: 23327–23334 (1998). ride cotransporter family. J. Biol. Chem., 271: 16237–16244 42) Yu, X. X., Mao, W., Zhong, A., Schow, P., Brush, J., Sherwood, (1996). S.W.,Adams,S.H.andPan,G.:Characterizationofnovel 28) Mount, D. B., Mercado, A., Song, L., Xu, J., George, A. L., Del- UCP5/BMCP1 isoforms and differential regulation of UCP4 and pire,E.andGamba,G.:CloningandcharacterizationofKCC3 UCP5 expression through dietary or temperature manipulation. and KCC4, new members of the cation-chloride cotransporter FASEB J., 14: 1611–1618 (2000). gene family. J. Biol. Chem., 274: 16355–16362 (1999). 43) Fiermonte, G., Palmieri, L., Todisco, S., Agrimi, G., Palmieri, F. 29) Caron, L., Rousseau, F., Gagnon, ÁE. and Isenring, P.: Cloning and Walker, J. E.: Identification of the mitochondrial glutamate and functional characterization of a cation-Cl－ cotransporter- transporter. Bacterial expression, reconstitution, functional interacting protein. J. Biol. Chem., 275: 32027–32036 (2000). characterization, and tissue distribution of two human isoforms. 30) Lee, A., Beck, L. and Markovich, D.: The human renal sodium J. Biol. Chem., 277: 19289–19294 (2002). sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: or- 44) Li, F. Y., Nikali, K., Gregan, J., Leibiger, I., Leibiger, B., ganization, chromosomal localization, and functional charac- Schweyen, R., Larsson, C. and Suomalainen, A.: Characteriza- terization. Genomics, 70: 354–363 (2000). tion of a novel human putative mitochondrial transporter 31) Girard, J. P., Baekkevold, E. S., Feliu, J., Brandtzaeg, P. and homologous to the yeast mitochondrial RNA splicing proteins 3 Amalric, F.: Molecular cloning and functional analysis of SUT-1, and 4. FEBS Lett., 494: 79–84 (2001). a sulfate transporter from human high endothelial venules. Proc. 45) Huizing, M., Iacobazzi, V., Ijlst, L., Savelkoul, P., Ruitenbeek, Natl. Acad. Sci. USA, 96: 12772–12777 (1999). W., van den Heuvel, L., Indiveri, C., Smeitink, J., Trijbels, F., 32) Inoue, K., Zhuang, L. and Ganapathy, V.: Human Na＋-coupled Wanders, R. and Palmieri, F.: Cloning of the human carnitine- citrate transporter: primary structure, genomic organization, acylcarnitine carrier cDNA and identification of the molecular and transport function. Biochem. Biophys. Res. Commun., 299: defect in a patient. Am.J.Hum.Genet., 61: 1239–1245 (1997). 465–471 (2002). 46) Dolce, V., Scarcia, P., Iacopetta, D. and Palmieri, F.: A fourth 33) Miyamoto, K., Tatsumi, S., Sonoda, T., Yamamoto, H., Minami, ADP/ATP carrier isoform in man: identification, bacterial ex- H., Taketani, Y. and Takeda, E.: Cloning and functional expres- pression, functional characterization and tissue distribution. sion of a Na＋-dependent phosphate co-transporter from human FEBS Lett., 579: 633–637 (2005). kidney: cDNA cloning and functional expression. Biochem. J., 47) Regeer, R. R., Lee, A. and Markovich, D.: Characterization of 305: 81–85 (1995). the human sulfate anion transporter (hsat-1) protein and gene 34) Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., (SAT1; SLC26A1). DNA Cell Biol., 22: 107–117 (2003). Hori,T.,Yamada,S.,Tomura,H.,Yamada,Y.,Inoue,I.,Koji- 48) Vincourt, J. B., Jullien, D., Kossida, S., Amalric, F. and Girard, J. ma, I. and Takeda, J.: Molecular cloning of a novel brain-type P.: Molecular cloning of SLC26A7, a novel member of the Na＋-dependent inorganic phosphate cotransporter. J. Neu- SLC26 sulfate/anion transporter family, from high endothelial rochem., 74: 2622–2625 (2000). venules and kidney. Genomics, 79: 249–256 (2002). 35) Prasad,P.D.,Ramamoorthy,S.,Leibach,F.H.andGanapathy, 49) Martin, G., Nemoto, M., Gelman, L., Geffroy, S., Najib, J., V.: Molecular cloning of the human placental folate transporter. Fruchart, J. C., Roevens, P., de Martinville, B., Deeb, S. and Biochem. Biophys. Res. Commun., 206: 681–687 (1995). Auwerx, J.: The human fatty acid transport protein-1 (SLC27A1; 36) Dutta, B., Huang, W., Molero, M., Kekuda, R., Leibach, F. H., FATP-1) cDNA and gene: organization, chromosomal localiza- Devoe, L. D., Ganapathy, V. and Prasad, P. D.: Cloning of the tion, and expression. Genomics, 66: 296–304 (2000). human thiamine transporter, a member of the folate transporter 50) Gimeno, R. E., Ortegon, A. M., Patel, S., Punreddy, S., Ge, P., family. J. Biol. Chem., 274: 31925–31929 (1999). Sun, Y., Lodish, H. F. and Stahl, A.: Characterization of a heart- 37) Eudy, J. D., Spiegelstein, O., Barber, R. C., Wlodarczyk, B. J., specific fatty acid transport protein. J. Biol. Chem., 278: Talbot, J. and Finnell, R. H.: Identification and characterization 16039–16044 (2003). of the human and mouse SLC19A3 gene: a novel member of the 51) Chimienti, F., Devergnas, S., Favier, A. and Seve, M.: Identifica- reduced folate family of micronutrient transporter genes. Mol. tion and cloning of a beta-cell-specific zinc transporter, ZnT-8, Genet. Metab., 71: 581–590 (2000). localized into insulin secretory granules. Diabetes, 53: 38) del Arco, A., Agudo, M. and Satrustegui, J.: Characterization of 2330–2337 (2004). a second member of the subfamily of calcium-binding mitochon- 52) Zhou, B. and Gitschier, J.: hCTR1: a human gene for copper up- drial carriers expressed in human non-excitable tissues. take identified by complementation in yeast. Proc. Natl. Acad. Biochem. J., 345 Pt 3: 725–732 (2000). Sci. USA, 94: 7481–7486 (1997). 39) Fiermonte, G., Dolce, V., David, L., Santorelli, F. M., Dionisi-Vi- 53) McIntire,S.L.,Reimer,R.J.,Schuske,K.,Edwards,R.H.and ci, C., Palmieri, F. and Walker, J. E.: The mitochondrial or- Jorgensen, E. M.: Identification and characterization of the nithine transporter. Bacterial expression, reconstitution, func- vesicular GABA transporter. Nature, 389: 870–876 (1997). tional characterization, and tissue distribution of two human 54) Kanamori,A.,Nakayama,J.,Fukuda,M.N.,Stallcup,W.B., isoforms. J. Biol. Chem., 278: 32778–32783 (2003). Sasaki, K., Fukuda, M. and Hirabayashi, Y. Expression cloning 40) del Arco, A. and Satrustegui, J.: Identification of a novel human and characterization of a cDNA encoding a novel membrane subfamily of mitochondrial carriers with calcium-binding protein required for the formation of O-acetylated ganglioside: a domains. J. Biol. Chem., 279: 24701–24713 (2004). putative acetyl-CoA transporter. Proc.Natl.Acad.Sci.USA, 94: 41) del Arco, A. and Satrustegui, J.: Molecular cloning of Aralar, a 2897–2902 (1997). 44 Masuhiro NISHIMURA and Shinsaku NAITO

55) Magagnin, S., Werner, A., Markovich, D., Sorribas, V., Stange, hepatic xenobiotic transporter mRNA up- and down-regulation G.,Biber,J.andMurer,H.:Expressioncloningofhumanand induced by overdose of fat-free total parenteral nutrition in in- rat renal cortex Na/Pi cotransport. Proc. Natl. Acad. Sci. USA, fant rats. Drug Metab. Pharmacokinet., 20: 46–54 (2005). 90: 5979–5983 (1993). 65) Nishimura,M.,Koeda,A.,Suzuki,E.,Kawano,Y.,Nakayama, 56) Xu, H., Bai, L., Collins, J. F. and Ghishan, F. K.: Molecular clon- M.,Satoh,T.,Narimatsu,S.andNaito,S.:RegulationofmRNA ing, functional characterization, tissue distribution, and chro- expression of MDR1, MRP1, MRP2 and MRP3 by prototypical mosomal localization of a human, small intestinal sodium- microsomal enzyme inducers in primary cultures of human and phosphate (Na＋-Pi) transporter (SLC34A2). Genomics, 62: rat hepatocytes. Drug Metab. Pharmacokinet., 21: 297–307 281–284 (1999). (2006). 57) Gaither, L. A. and Eide, D. J.: The human ZIP1 transporter 66) Nishimura, M., Yamauchi, A., Yamaguchi, M., Ueda, N. and mediates zinc uptake in human K562 erythroleukemia cells. J. Naito, S.: Major role of soybean oil in preventing decrease in Biol. Chem., 276: 22258–22264 (2001). CYP4A1 mRNA content relative to PPARalpha mRNA down- 58) Wang,F.,Kim,B.E.,Petris,M.J.andEide,D.J.:Themam- regulation in infant rats. Biol. Pharm. Bull., 28: 1517–1520 malian Zip5 protein is a zinc transporter that localizes to the (2005). basolateral surface of polarized cells. J. Biol. Chem., 279: 67) Nishimura, M., Ueda, N. and Naito S.: Effects of dimethyl sul- 51433–51441 (2004). foxide on the gene induction of cytochrome P450 isoforms, 59) Nishimura,M.,Yoshitsugu,H.,Naito,S.andHiraoka,I.:Evalu- UGT-dependent glucuronosyl transferase isoforms, and ABCB1 ation of gene induction of drug-metabolizing enzymes and in primary culture of human hepatocytes. Biol. Pharm. Bull., 26: transporters in primary culture of human hepatocytes using 1052–1056 (2003). high-sensitivity real-time reverse transcription PCR. Yakugaku 68) Nishimura, M., Imai, T., Morioka, Y., Kuribayashi, S., Kamataki, Zasshi, 122: 339–361 (2002). T. and Naito, S.: Effects of NO-1886 (Ibrolipim), a lipoprotein 60) Nishimura, M., Yaguti, H., Yoshitsugu, H., Naito, S. and Satoh, lipase-promoting agent, on gene induction of cytochrome T.: Tissue distribution of mRNA expression of human P450s, carboxylesterases, and sulfotransferases in primary cul- cytochrome P450 isoforms assessed by high-sensitivity real-time tures of human hepatocytes. Drug Metab. Pharmacokinet., 19: reverse transcription PCR. Yakugaku Zasshi, 123: 369–375 422–429 (2004). (2003). 69) Nishimura,M.,Yokoi,T.,Tateno,C.,Kataoka,M.,Takahashi, 61) Nishimura, M., Koeda, A., Suganuma, Y., Suzuki, E., Shimizu, E., Horie, T., Yoshizato, K. and Naito, S.: Induction of human T., Nakayama, M., Satoh, T., Narimatsu, S. and Naito, S.: Com- CYP1A2 and CYP3A4 in primary culture of hepatocytes from parison of inducibility of CYP1A and CYP3A mRNAs by proto- chimeric mice with humanized liver. Drug Metab. Pharmacoki- typical inducers in primary cultures of human, cynomolgus net., 20: 121–126 (2005). monkey, and rat hepatocytes. Drug Metab. Pharmacokinet., 22: 70) Morioka,Y.,Nishimura,M.,Imai,T.,Suzuki,S.,Harada,M., 178–186 (2007). Satoh, T. and Naito, S.: Assessment of induction of cytochrome 62) Katoh, M., Matsui, T., Okumura, H., Nakajima, M., Nishimura, P450 by NO-1886 (ibrolipim), a lipoprotein lipase-promoting a- M.,Naito,S.,Tateno,C.,Yoshizato,K.andYokoi,T.:Expres- gent, in primary cultures of human hepatocytes and in female sion of human phase II enzymes in chimeric mice with hu- rat liver. Drug Metab. Pharmacokinet., 21: 19–28 (2006). manized liver. Drug Metab. Dispos., 33: 1333–1340 (2005). 71) Yoshitsugu,H.,Nishimura,M.,Tateno,C.,Kataoka,M.,Taka- 63) Miyano, J., Yamamoto, S., Hanioka, N., Narimatsu, S., Ishikawa, hashi, E., Soeno, Y., Yoshizato, K., Yokoi, T. and Naito, S.: T., Ogura, K., Watabe, T., Nishimura, M., Ueda, N. and Naito, Evaluation of human CYP1A2 and CYP3A4 mRNA expression S.: Involvement of SULT1A3 in elevated sulfation of 4-hydrox- in hepatocytes from chimeric mice with humanized liver. Drug ypropranolol in Hep G2 cells pretreated with beta-naphthofla- Metab. Pharmacokinet., 21: 465–474 (2006). vone. Biochem. Pharmacol., 69: 941–950 (2005). 72) Nishimura, M. and Naito, S.: Tissue-specific mRNA expression 64) Nishimura, M., Yamaguchi, M., Yamauchi, A., Ueda, N. and profiles of human carbohydrate sulfotransferase and tyrosyl- Naito, S.: Role of soybean oil fat emulsion in the prevention of protein sulfotransferase. Biol.Pharm.Bull., 30: 821–825 (2007).