SLC22A1 (O15245) variants and mutations
SLC22A1 (also known as O15245) is a human protein-coding gene encoding a solute carrier family 22 member 1 protein. It mediates uptake of organic cations from portal blood into hepatocytes and influences clearance of multiple drugs. Functional variants can alter exposure or response to substrates such as metformin, although clinical effects are drug and allele dependent. This analysis covers 994 SLC22A1 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes Hypercholesterolemia, coronary artery disorder, and metabolic disease. Example SLC22A1 variants include P2L, P2S, and P2T.
Variant analysis overview
- Gene: SLC22A1
- Protein: O15245
- UniProt accession: O15245
- Organism: Homo sapiens
- Variants analyzed: 994
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 689 unspecified-consequence records; 146 missense variants; 124 synonymous variants; 7 stop-gained variants; 19 frameshift variants; 5 splice-region variants; 2 in-frame deletions; 1 in-frame insertions; 1 substitution
- Prediction scores: 822 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Hypercholesterolemia, coronary artery disorder, metabolic disease, myocardial ischemia, familial hyperlipidemia, coronary atherosclerosis, response to statin, hyperlipidemia, Disorder of lipid metabolism, cardiovascular disorder, angina pectoris, atherosclerosis.
Protein structure and variant hotspots
- Protein features: 12 transmembrane segments; 3 post-translational modification sites.
- Structural context: 404 variants have structural context.
- PTM context: 5 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SLC22A1 variants
Examples include P2L, P2S, P2T, P2P, T3P, T3S, T3T, V4A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), Ensembl rs1583318072, REVEL 0.10, CADD 10.60
- P2S (p.Pro2Ser), NCI-TCGA Cosmic COSV6145, cosmic curated COSV61452, Variant assessed as somatic; moderate impact.
- P2T (p.Pro2Thr), gnomAD 6-160121939-C-A, REVEL 0.13, CADD 8.35
- P2P (p.Pro2Pro), rs187313078, gnomAD 6-160121941-C-T, CADD 3.92
- T3P (p.Thr3Pro), gnomAD 6-160121942-A-C, REVEL 0.35, CADD 20.40
- T3S (p.Thr3Ser), gnomAD 6-160121942-A-T, REVEL 0.06, CADD 5.97
- T3T (p.Thr3Thr), rs780092171, gnomAD 6-160121944-C-G, CADD 0.24
- V4A (p.Val4Ala), TOPMed rs1779938811, gnomAD rs1779938811, REVEL 0.33, CADD 16.60
- V4L (p.Val4Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V4M (p.Val4Met), rs756880870, ExAC rs756880870, gnomAD rs756880870, REVEL 0.17, CADD 3.36, Variant assessed as somatic; moderate impact.
- V4V (p.Val4Val), rs780717864, gnomAD 6-160121947-G-A, CADD 1.13
- D5N (p.Asp5Asn), gnomAD 6-160121948-G-A, REVEL 0.63, CADD 24.90
- D5E (p.Asp5Glu), gnomAD 6-160121950-T-G, REVEL 0.53, CADD 2.02
- D6N (p.Asp6Asn), gnomAD 6-160121951-G-A, REVEL 0.44, CADD 23.70
- D6D (p.Asp6Asp), gnomAD 6-160121953-C-T, CADD 0.17
- I7V (p.Ile7Val), gnomAD 6-160121954-A-G, REVEL 0.10, CADD 0.73
- L8L (p.Leu8Leu), gnomAD 6-160121957-C-T, CADD 4.59
- E9Q (p.Glu9Gln), gnomAD rs1387697215, REVEL 0.21, CADD 16.30
- E9* (p.Glu9Ter), gnomAD 6-160121960-G-T, CADD 35.00
- E9E (p.Glu9Glu), gnomAD 6-160121962-G-A, CADD 6.38
- Q10* (p.Gln10Ter), gnomAD 6-160121963-C-T, CADD 35.00
- Q10E (p.Gln10Glu), gnomAD 6-160121963-C-G, REVEL 0.07, CADD 8.22
- Q10K (p.Gln10Lys), gnomAD 6-160121963-C-A, REVEL 0.08, CADD 14.60
- Q10H (p.Gln10His), gnomAD 6-160121965-G-C, REVEL 0.06, CADD 4.99
- V11A (p.Val11Ala), rs749926302, ClinGen CA4083575, ClinVar RCV004448700, ExAC rs749926302, REVEL 0.24, CADD 14.20, Uncertain significance, not specified
- V11D (p.Val11Asp), ExAC rs749926302, TOPMed rs749926302, gnomAD rs749926302, REVEL 0.62, CADD 23.60, Uncertain significance
- V11G (p.Val11Gly), ExAC rs749926302, TOPMed rs749926302, gnomAD rs749926302, REVEL 0.46, CADD 22.10, Uncertain significance
- V11I (p.Val11Ile), gnomAD 6-160121966-G-A, REVEL 0.10, CADD 0.62
- G12E (p.Gly12Glu), ExAC rs756098824, TOPMed rs756098824, gnomAD rs756098824, REVEL 0.93, CADD 25.70
- G12G (p.Gly12Gly), gnomAD 6-160121971-G-A, CADD 7.41
- E13G (p.Glu13Gly), gnomAD 6-160121973-A-G, REVEL 0.14, CADD 16.60
- S14A (p.Ser14Ala), ExAC rs779866607, gnomAD rs779866607, REVEL 0.29, CADD 23.00
- S14C (p.Ser14Cys), 1000Genomes rs34447885, ESP rs34447885, ExAC rs34447885, TOPMed rs34447885
- S14F (p.Ser14Phe), rs34447885, UniProt VAR 043319, 1000Genomes rs34447885, ESP rs34447885, REVEL 0.14, CADD 15.30, Benign
- S14P (p.Ser14Pro), ExAC rs779866607, gnomAD rs779866607, REVEL 0.31, CADD 23.40
- G15D (p.Gly15Asp), gnomAD 6-160121979-G-A, REVEL 0.42, CADD 20.00
- G15G (p.Gly15Gly), rs150955307, gnomAD 6-160121980-C-T, CADD 9.47
- W16C (p.Trp16Cys), gnomAD rs1226022756, REVEL 0.48, CADD 22.60
- W16L (p.Trp16Leu), TOPMed rs1374644494, gnomAD rs1374644494, REVEL 0.14, CADD 17.40
- W16* (p.Trp16Ter), gnomAD 6-160121983-G-A, CADD 35.00
- F17F (p.Phe17Phe), rs778751631, gnomAD 6-160121986-C-T, CADD 10.70
- Q18R (p.Gln18Arg), gnomAD rs1328983401, REVEL 0.94, CADD 25.70
- Q18P (p.Gln18Pro), rs1779940535, gnomAD 6-160121983-G-GT, CADD 28.10
- Q18Q (p.Gln18Gln), gnomAD 6-160121989-G-A, CADD 8.96
- K19K (p.Lys19Lys), gnomAD 6-160121992-G-A, CADD 8.77
- Q20* (p.Gln20Ter), TOPMed rs931277008, CADD 34.00
- Q20H (p.Gln20His), Ensembl rs1779941284, REVEL 0.44, CADD 18.90
- Q20E (p.Gln20Glu), gnomAD 6-160121993-C-G, REVEL 0.37, CADD 16.80
- A21V (p.Ala21Val), TOPMed rs980071986, REVEL 0.06, CADD 3.53
- A21P (p.Ala21Pro), gnomAD 6-160121996-G-C, REVEL 0.58, CADD 16.90
- A21A (p.Ala21Ala), gnomAD 6-160121998-C-T, CADD 7.85
- F22Y (p.Phe22Tyr), gnomAD rs1779941539, REVEL 0.58, CADD 24.80
- F22F (p.Phe22Phe), rs1779941650, gnomAD 6-160122001-C-T, CADD 5.76
- L23V (p.Leu23Val), 1000Genomes rs34570655, ESP rs34570655, ExAC rs34570655, TOPMed rs34570655, REVEL 0.12, CADD 7.07
- L23F (p.Leu23Phe), gnomAD 6-160122002-C-T, REVEL 0.11, CADD 3.02
- L23L (p.Leu23Leu), rs1264548911, gnomAD 6-160122004-C-T, CADD 1.54
- I24T (p.Ile24Thr), Ensembl rs2114760599
- I24V (p.Ile24Val), NCI-TCGA Cosmic COSV6145, cosmic curated COSV61452, Variant assessed as somatic; moderate impact.
- L25S (p.Leu25Ser), rs1440356481, ClinGen CA366343589, ClinVar RCV004118055, gnomAD rs1440356481, REVEL 0.64, CADD 22.90, Uncertain significance, not specified
- C26R (p.Cys26Arg), ExAC rs772420367, gnomAD rs772420367, REVEL 0.66, CADD 22.80
- C26G (p.Cys26Gly), gnomAD 6-160122011-T-G, REVEL 0.48, CADD 18.60
- C26C (p.Cys26Cys), gnomAD 6-160122013-C-T, CADD 1.29
- L27L (p.Leu27Leu), gnomAD 6-160122014-C-T, CADD 3.06
- L27P (p.Leu27Pro), gnomAD 6-160122015-T-C, REVEL 0.62, CADD 22.90
- L28L (p.Leu28Leu), rs1232993903, gnomAD 6-160122017-C-T, CADD 0.38
- L28P (p.Leu28Pro), gnomAD 6-160122018-T-C, REVEL 0.45, CADD 14.60
- S29* (p.Ser29Ter), cosmic curated COSV10462, ExAC rs375175439, TOPMed rs375175439, gnomAD rs375175439, CADD 34.00
- S29L (p.Ser29Leu), cosmic curated COSV61454, ExAC rs375175439, TOPMed rs375175439, gnomAD rs375175439, REVEL 0.52, CADD 22.70
- S29P (p.Ser29Pro), gnomAD 6-160122020-T-C, REVEL 0.58, CADD 20.20
- S29S (p.Ser29Ser), rs760852994, gnomAD 6-160122022-G-A, CADD 0.03
- A30P (p.Ala30Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A30T (p.Ala30Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A30G (p.Ala30Gly), gnomAD 6-160122024-C-G, REVEL 0.30, CADD 4.71
- A30V (p.Ala30Val), gnomAD 6-160122024-C-T, REVEL 0.12, CADD 0.05
- A31T (p.Ala31Thr), TOPMed rs1779942798, REVEL 0.10, CADD 0.20
- A31V (p.Ala31Val), TOPMed rs1228388059, gnomAD rs1228388059, REVEL 0.10, CADD 4.74
- F32L (p.Phe32Leu), gnomAD rs1410949623, REVEL 0.15, CADD 0.01
- A33T (p.Ala33Thr), TOPMed rs1348942638, gnomAD rs1348942638, REVEL 0.12, CADD 13.70
- A33V (p.Ala33Val), rs550392111, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10026, 1000Genomes rs550392111, REVEL 0.48, CADD 14.80, Variant assessed as somatic; moderate impact.
- A33A (p.Ala33Ala), rs560595462, gnomAD 6-160122034-G-A, CADD 0.90
- P34S (p.Pro34Ser), gnomAD 6-160122035-C-T, REVEL 0.36, CADD 13.20
- P34P (p.Pro34Pro), rs1331835554, gnomAD 6-160122037-C-T, CADD 1.80
- I35M (p.Ile35Met), Ensembl rs987557499, REVEL 0.34, CADD 19.80
- I35T (p.Ile35Thr), ExAC rs765568729, gnomAD rs765568729, REVEL 0.33, CADD 22.00
- I35V (p.Ile35Val), gnomAD rs1413015471, REVEL 0.13, CADD 0.02
- I35G (p.Ile35Gly), rs776450090, gnomAD 6-160122036-CCATC, CADD 24.20
- I35L (p.Ile35Leu), gnomAD 6-160122038-A-C, REVEL 0.17, CADD 0.20
- I35F (p.Ile35Phe), gnomAD 6-160122038-A-T, REVEL 0.22, CADD 0.69
- C36R (p.Cys36Arg), Ensembl rs1360714589
- C36S (p.Cys36Ser), ExAC rs753028126, TOPMed rs753028126, gnomAD rs753028126, REVEL 0.22, CADD 15.40
- C36W (p.Cys36Trp), TOPMed rs1415661322, gnomAD rs1415661322, REVEL 0.28, CADD 10.50
- C36Y (p.Cys36Tyr), ExAC rs753028126, TOPMed rs753028126, gnomAD rs753028126, REVEL 0.16, CADD 5.81
- C36C (p.Cys36Cys), gnomAD 6-160122043-T-C, CADD 1.29
- V37L (p.Val37Leu), ExAC rs761516344, gnomAD rs761516344, REVEL 0.14, CADD 16.90
- V37M (p.Val37Met), ExAC rs761516344, gnomAD rs761516344, REVEL 0.45, CADD 18.80
- V37A (p.Val37Ala), gnomAD 6-160122045-T-C, REVEL 0.53, CADD 18.20
- V37V (p.Val37Val), rs750016388, gnomAD 6-160122046-G-A, CADD 4.92
- G38D (p.Gly38Asp), 1000Genomes rs35888596, ESP rs35888596, ExAC rs35888596, TOPMed rs35888596, REVEL 0.89, CADD 24.30
- G38V (p.Gly38Val), 1000Genomes rs35888596, ESP rs35888596, ExAC rs35888596, TOPMed rs35888596
- I39M (p.Ile39Met), ExAC rs749535980, TOPMed rs749535980, gnomAD rs749535980, REVEL 0.54, CADD 18.30
- I39I (p.Ile39Ile), rs749535980, gnomAD 6-160122052-C-T, CADD 3.79
- V40F (p.Val40Phe), cosmic curated COSV61451, ExAC rs753772607, TOPMed rs753772607, gnomAD rs753772607, Uncertain significance
- V40I (p.Val40Ile), rs753772607, ClinGen CA4083596, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10026, REVEL 0.37, CADD 17.30, Uncertain significance, not specified
- V40V (p.Val40Val), rs946248370, gnomAD 6-160122055-C-G, CADD 2.94
- F41L (p.Phe41Leu), rs2297373, UniProt VAR 043320, ExAC rs2297373, TOPMed rs2297373, REVEL 0.85, CADD 23.00
- F41S (p.Phe41Ser), gnomAD 6-160122057-T-C, REVEL 0.89, CADD 25.70
- F41F (p.Phe41Phe), rs2297373, gnomAD 6-160122058-C-T, CADD 6.66
- L42R (p.Leu42Arg), rs778919765, ClinGen CA4083598, ClinVar RCV004283680, ExAC rs778919765, REVEL 0.83, CADD 23.50, Uncertain significance, not specified
- G43C (p.Gly43Cys), gnomAD 6-160122062-G-T, REVEL 0.69, CADD 25.20
- G43G (p.Gly43Gly), rs747942721, gnomAD 6-160122064-T-C, CADD 5.00
- T45I (p.Thr45Ile), cosmic curated COSV61452, 1000Genomes rs190270215, ExAC rs190270215, TOPMed rs190270215, REVEL 0.11, CADD 4.50
- T45R (p.Thr45Arg), 1000Genomes rs190270215, ExAC rs190270215, TOPMed rs190270215, gnomAD rs190270215, REVEL 0.58, CADD 10.10
- P46A (p.Pro46Ala), ExAC rs747192524, gnomAD rs747192524
- P46H (p.Pro46His), TOPMed rs1779946897
- P46S (p.Pro46Ser), NCI-TCGA Cosmic COSV6145, cosmic curated COSV61452, Variant assessed as somatic; moderate impact.
- P46T (p.Pro46Thr), ExAC rs747192524, gnomAD rs747192524, REVEL 0.73, CADD 22.60
- P46P (p.Pro46Pro), rs1480737283, gnomAD 6-160122073-T-C, CADD 0.30
- D47N (p.Asp47Asn), TOPMed rs1201270394, gnomAD rs1201270394
- H48R (p.His48Arg), Ensembl rs1779947322, REVEL 0.83, CADD 22.30
- H48Y (p.His48Tyr), TOPMed rs1375763941, gnomAD rs1375763941, REVEL 0.54, CADD 20.80
- H49Q (p.His49Gln), TOPMed rs1270367995, gnomAD rs1270367995
- H49R (p.His49Arg), ExAC rs770936405, gnomAD rs770936405, REVEL 0.19, CADD 0.00
- H49P (p.His49Pro), rs1477152702, gnomAD 6-160122079-CCACT, CADD 25.10
- H49Y (p.His49Tyr), gnomAD 6-160122080-C-T, REVEL 0.10, CADD 0.62
- H49H (p.His49His), rs1270367995, gnomAD 6-160122082-C-T, CADD 0.67
- C50F (p.Cys50Phe), ExAC rs776750054, gnomAD rs776750054
- C50R (p.Cys50Arg), rs931225163, Ensembl rs931225163, AlphaMissense 0.93, MetaLR 0.88, Variant assessed as somatic; moderate impact.
- C50L (p.Cys50Leu), rs1779947758, gnomAD 6-160122082-C-CT, CADD 24.30
- S52R (p.Ser52Arg), 1000Genomes rs1867351, ESP rs1867351, ExAC rs1867351, TOPMed rs1867351, REVEL 0.44, CADD 21.00
- S52S (p.Ser52Ser), rs1867351, gnomAD 6-160122091-T-C, CADD 5.37
- P53S (p.Pro53Ser), gnomAD 6-160122092-C-T, REVEL 0.52, CADD 19.60
- P53A (p.Pro53Ala), gnomAD 6-160122092-C-G, REVEL 0.50, CADD 22.00
- P53R (p.Pro53Arg), gnomAD 6-160122093-C-G, REVEL 0.66, CADD 22.90
- P53P (p.Pro53Pro), gnomAD 6-160122094-T-C, CADD 0.08
- G54W (p.Gly54Trp), gnomAD 6-160122095-G-T, REVEL 0.54, CADD 24.30
- G54E (p.Gly54Glu), gnomAD 6-160122096-G-A, REVEL 0.42, CADD 24.40
- G54G (p.Gly54Gly), rs770325988, gnomAD 6-160122097-G-A, CADD 5.79
- V55L (p.Val55Leu), rs1779948577, ClinGen CA366343881, ClinVar RCV004110299, AlphaMissense 0.21, MetaLR 0.46, Uncertain significance, not specified
- V55M (p.Val55Met), Ensembl rs1779948577
- V55V (p.Val55Val), rs775886657, gnomAD 6-160122100-G-A, CADD 8.50
- A56G (p.Ala56Gly), ExAC rs763318204, TOPMed rs763318204, gnomAD rs763318204, REVEL 0.17, CADD 18.80
- A56V (p.Ala56Val), ExAC rs763318204, TOPMed rs763318204, gnomAD rs763318204, REVEL 0.06, CADD 14.80
- E57K (p.Glu57Lys), TOPMed rs1305316089, gnomAD rs1305316089, REVEL 0.42, CADD 23.60, Uncertain significance, not specified
- E57G (p.Glu57Gly), gnomAD 6-160122099-T-TGG, CADD 25.50
- L58L (p.Leu58Leu), gnomAD 6-160122107-C-T, CADD 9.58
- S59N (p.Ser59Asn), TOPMed rs1028655210, REVEL 0.35, CADD 24.50
- S59G (p.Ser59Gly), gnomAD 6-160122110-A-G, REVEL 0.28, CADD 22.40
- S59S (p.Ser59Ser), rs760355786, gnomAD 6-160122112-C-T, CADD 10.60
- Q60* (p.Gln60Ter), ExAC rs765851174, TOPMed rs765851174, gnomAD rs765851174, CADD 35.00
- Q60K (p.Gln60Lys), ExAC rs765851174, TOPMed rs765851174, gnomAD rs765851174, REVEL 0.07, CADD 11.70
- Q60E (p.Gln60Glu), gnomAD 6-160122113-C-G, REVEL 0.06, CADD 6.36
- R61C (p.Arg61Cys), rs12208357, cosmic curated COSV10587, UniProt VAR 043321, 1000Genomes rs12208357, REVEL 0.28, CADD 23.70, Benign
- R61H (p.Arg61His), rs145649236, 1000Genomes rs145649236, ESP rs145649236, ExAC rs145649236, REVEL 0.34, CADD 23.40, Variant assessed as somatic; moderate impact.
- R61L (p.Arg61Leu), 1000Genomes rs145649236, ESP rs145649236, ExAC rs145649236, TOPMed rs145649236
- R61P (p.Arg61Pro), rs1341056789, gnomAD 6-160122115-G-GC, CADD 23.40
- C62F (p.Cys62Phe), TOPMed rs1779950213
- C62G (p.Cys62Gly), ExAC rs765280158, gnomAD rs765280158, REVEL 0.67, CADD 26.30
- G63S (p.Gly63Ser), ExAC rs752617602, TOPMed rs752617602, gnomAD rs752617602, REVEL 0.60, CADD 25.90
- W64* (p.Trp64Ter), Ensembl rs868041684, CADD 39.00
- W64C (p.Trp64Cys), NCI-TCGA Cosmic COSV6145, cosmic curated COSV61452, Variant assessed as somatic; moderate impact.
- W64S (p.Trp64Ser), Ensembl rs868041684
- W64R (p.Trp64Arg), gnomAD 6-160122125-T-C, REVEL 0.76, CADD 25.70
- S65C (p.Ser65Cys), gnomAD 6-160122128-A-T, REVEL 0.74, CADD 25.40
- S65R (p.Ser65Arg), gnomAD 6-160122130-C-G, REVEL 0.42, CADD 17.80
- S65S (p.Ser65Ser), rs758301867, gnomAD 6-160122130-C-T, CADD 6.58
- P66S (p.Pro66Ser), Ensembl rs867165669
- P66P (p.Pro66Pro), rs962154782, gnomAD 6-160122133-T-C, CADD 1.42
- A67V (p.Ala67Val), ExAC rs777661737, TOPMed rs777661737, gnomAD rs777661737, REVEL 0.24, CADD 8.77, Uncertain significance, not specified
- A67A (p.Ala67Ala), rs147756753, gnomAD 6-160122136-G-A, CADD 0.09
- E68D (p.Glu68Asp), NCI-TCGA Cosmic COSV6145, cosmic curated COSV61451, Variant assessed as somatic; moderate impact.
- E68K (p.Glu68Lys), gnomAD 6-160122137-G-A, REVEL 0.44, CADD 22.40
- E68E (p.Glu68Glu), rs2114761028, gnomAD 6-160122139-G-A, CADD 1.73
- E69K (p.Glu69Lys), gnomAD 6-160122140-G-A, REVEL 0.41, CADD 22.80
- E69D (p.Glu69Asp), gnomAD 6-160122142-G-T, REVEL 0.31, CADD 22.70
- L70M (p.Leu70Met), TOPMed rs1473907452, gnomAD rs1473907452, REVEL 0.38, CADD 21.60
- L70V (p.Leu70Val), TOPMed rs1473907452, gnomAD rs1473907452, REVEL 0.33, CADD 20.60, Uncertain significance, not specified
- L70L (p.Leu70Leu), gnomAD 6-160122143-C-T, CADD 4.85
- L70P (p.Leu70Pro), gnomAD 6-160122144-T-C, REVEL 0.60, CADD 22.10
- N71D (p.Asn71Asp), ExAC rs757470546, TOPMed rs757470546, gnomAD rs757470546, REVEL 0.37, CADD 23.40
- N71S (p.Asn71Ser), ESP rs149135239, ExAC rs149135239, TOPMed rs149135239, gnomAD rs149135239, REVEL 0.34, CADD 21.70
Public SLC22A1 analysis runs
- SLC22A1 analysis run — SLC22A1 (994 variants) — completed 2026-08-18