SLC12A2 (P55011) variants and mutations
SLC12A2 (also known as P55011) is a human protein-coding gene encoding a solute carrier family 12 member 2 protein. It brings sodium, potassium, and chloride into cells and supports cell-volume control, epithelial secretion, and neuronal chloride homeostasis. Pathogenic variants can cause developmental disorders with hearing loss, growth abnormalities, or neurologic impairment. This analysis covers 1,754 SLC12A2 variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes Delpire-McNeill syndrome, hearing loss, autosomal dominant 78, and Kilquist syndrome. Example SLC12A2 variants include E2Q, E2*, and E2K.
Variant analysis overview
- Gene: SLC12A2
- Protein: P55011
- UniProt accession: P55011
- Organism: Homo sapiens
- Variants analyzed: 1754
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 1,266 unspecified-consequence records; 12 stop-gained variants; 319 missense variants; 12 in-frame deletions; 94 synonymous variants; 47 frameshift variants; 2 in-frame insertions; 2 substitution
- Prediction scores: 1,421 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Delpire-McNeill syndrome, hearing loss, autosomal dominant 78, Kilquist syndrome, Varicose veins, Intellectual disability, hearing loss disorder, Abnormality of the skeletal system, cellulitis, hypothyroidism, hereditary disease, lymphatic system disorder, edema.
Protein structure and variant hotspots
- Protein features: 12 transmembrane segments; 21 binding sites; 15 post-translational modification sites.
- Structural context: 226 variants have structural context.
- PTM context: 21 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 SLC12A2 variants
Examples include E2Q, E2*, E2K, E2G, E2V, E2E, E2D, P3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2Q (p.Glu2Gln), rs2480679879, ClinGen CA360735620, ClinVar RCV003821310, REVEL 0.31, CADD 22.30, Uncertain significance, not provided
- E2* (p.Glu2Ter), gnomAD 5-128083958-G-T, CADD 35.00
- E2K (p.Glu2Lys), gnomAD 5-128083958-G-A, REVEL 0.33, CADD 19.10
- E2G (p.Glu2Gly), gnomAD 5-128083959-A-G, REVEL 0.32, CADD 22.80
- E2V (p.Glu2Val), gnomAD 5-128083959-A-T, REVEL 0.32, CADD 22.70
- E2E (p.Glu2Glu), gnomAD 5-128083960-G-A, CADD 5.38
- E2D (p.Glu2Asp), gnomAD 5-128083960-G-T, REVEL 0.23, CADD 9.72
- P3L (p.Pro3Leu), TOPMed rs903367629, REVEL 0.24, CADD 19.90
- P3A (p.Pro3Ala), gnomAD 5-128083961-C-G, REVEL 0.24, CADD 18.70
- P3S (p.Pro3Ser), gnomAD 5-128083961-C-T, REVEL 0.25, CADD 20.10
- P3T (p.Pro3Thr), gnomAD 5-128083961-C-A, REVEL 0.24, CADD 19.30
- P3Q (p.Pro3Gln), gnomAD 5-128083962-C-A, REVEL 0.25, CADD 19.10
- P3R (p.Pro3Arg), gnomAD 5-128083962-C-G, REVEL 0.23, CADD 19.10
- P3P (p.Pro3Pro), gnomAD 5-128083963-G-T, CADD 7.32
- R4Q (p.Arg4Gln), TOPMed rs999011794, gnomAD rs999011794, REVEL 0.24, CADD 12.60
- R4W (p.Arg4Trp), TOPMed rs1315325838, gnomAD rs1315325838, REVEL 0.22, CADD 19.30
- p.Arg4 Pro8del, rs1759904941, gnomAD 5-128083959-AGCCG, CADD 16.70
- R4G (p.Arg4Gly), gnomAD 5-128083963-GC-G, CADD 18.60
- R4R (p.Arg4Arg), gnomAD 5-128083964-C-A, CADD 7.81
- R4P (p.Arg4Pro), gnomAD 5-128083965-G-C, REVEL 0.24, CADD 14.30
- R4L (p.Arg4Leu), gnomAD 5-128083965-G-T, REVEL 0.26, CADD 13.60
- P5S (p.Pro5Ser), gnomAD 5-128083967-C-T, REVEL 0.23, CADD 13.90
- P5T (p.Pro5Thr), gnomAD 5-128083967-C-A, REVEL 0.19, CADD 13.70
- P5A (p.Pro5Ala), gnomAD 5-128083967-C-G, REVEL 0.22, CADD 12.10
- P5R (p.Pro5Arg), gnomAD 5-128083968-C-G, REVEL 0.27, CADD 16.20
- P5L (p.Pro5Leu), gnomAD 5-128083968-C-T, REVEL 0.21, CADD 17.10
- P5H (p.Pro5His), gnomAD 5-128083968-C-A, REVEL 0.32, CADD 15.90
- P5P (p.Pro5Pro), gnomAD 5-128083969-C-T, CADD 10.80
- T6K (p.Thr6Lys), gnomAD rs1759925274, REVEL 0.23, CADD 13.90
- T6P (p.Thr6Pro), gnomAD 5-128083970-A-C, REVEL 0.35, CADD 10.80
- T6A (p.Thr6Ala), gnomAD 5-128083970-A-G, REVEL 0.26, CADD 6.60
- T6M (p.Thr6Met), gnomAD 5-128083971-C-T, REVEL 0.31, CADD 15.20
- T6R (p.Thr6Arg), gnomAD 5-128083971-C-G, REVEL 0.30, CADD 13.70
- T6T (p.Thr6Thr), gnomAD 5-128083972-G-A, CADD 9.95
- A7S (p.Ala7Ser), TOPMed rs1051964251, REVEL 0.27, CADD 14.50
- A7P (p.Ala7Pro), gnomAD 5-128083973-G-C, REVEL 0.33, CADD 19.70
- A7T (p.Ala7Thr), gnomAD 5-128083973-G-A, REVEL 0.31, CADD 19.20
- A7V (p.Ala7Val), gnomAD 5-128083974-C-T, REVEL 0.23, CADD 22.40
- A7G (p.Ala7Gly), gnomAD 5-128083974-C-G, REVEL 0.14, CADD 19.10
- A7E (p.Ala7Glu), gnomAD 5-128083974-C-A, REVEL 0.27, CADD 22.10
- A7A (p.Ala7Ala), gnomAD 5-128083975-G-T, CADD 13.10
- P8H (p.Pro8His), gnomAD rs1262237079, REVEL 0.29, CADD 23.50
- P8L (p.Pro8Leu), gnomAD rs1262237079, REVEL 0.33, CADD 22.40
- P8A (p.Pro8Ala), gnomAD 5-128083976-C-G, REVEL 0.30, CADD 20.80
- P8S (p.Pro8Ser), gnomAD 5-128083976-C-T, REVEL 0.39, CADD 22.20
- P8T (p.Pro8Thr), gnomAD 5-128083976-C-A, REVEL 0.29, CADD 21.70
- P8R (p.Pro8Arg), gnomAD 5-128083977-C-G, REVEL 0.31, CADD 22.60
- P8P (p.Pro8Pro), rs1055755542, gnomAD 5-128083978-C-T, CADD 13.20
- S9P (p.Ser9Pro), gnomAD 5-128083975-GC-G, CADD 23.60
- S9T (p.Ser9Thr), gnomAD 5-128083979-T-A, REVEL 0.26, CADD 17.80
- S9W (p.Ser9Trp), gnomAD 5-128083979-TCCTC, CADD 24.30
- S9C (p.Ser9Cys), gnomAD 5-128083980-C-G, REVEL 0.35, CADD 21.80
- S9Y (p.Ser9Tyr), gnomAD 5-128083980-C-A, REVEL 0.31, CADD 21.00
- S9F (p.Ser9Phe), gnomAD 5-128083980-C-T, REVEL 0.32, CADD 21.80
- S9S (p.Ser9Ser), gnomAD 5-128083981-C-G, CADD 11.90
- S10A (p.Ser10Ala), TOPMed rs1363346040, REVEL 0.24, CADD 15.60
- S10P (p.Ser10Pro), TOPMed rs1363346040, REVEL 0.21, CADD 17.90
- S10F (p.Ser10Phe), gnomAD 5-128083983-C-T, REVEL 0.20, CADD 19.30
- S10Y (p.Ser10Tyr), gnomAD 5-128083983-C-A, REVEL 0.22, CADD 21.70
- S10S (p.Ser10Ser), gnomAD 5-128083984-C-T, CADD 9.53
- G11S (p.Gly11Ser), TOPMed rs1759927162, REVEL 0.19, CADD 16.20
- G11A (p.Gly11Ala), gnomAD 5-128083982-TC-T, CADD 23.50
- G11C (p.Gly11Cys), gnomAD 5-128083985-G-T, REVEL 0.27, CADD 23.80
- G11D (p.Gly11Asp), gnomAD 5-128083986-G-A, REVEL 0.30, CADD 22.40
- G11V (p.Gly11Val), gnomAD 5-128083986-G-T, REVEL 0.31, CADD 22.40
- G11G (p.Gly11Gly), gnomAD 5-128083987-C-G, CADD 10.80
- A12D (p.Ala12Asp), TOPMed rs895786562, gnomAD rs895786562, REVEL 0.37, CADD 15.80
- A12G (p.Ala12Gly), TOPMed rs895786562, gnomAD rs895786562, REVEL 0.21, CADD 10.90
- A12V (p.Ala12Val), TOPMed rs895786562, gnomAD rs895786562, REVEL 0.32, CADD 11.80
- A12T (p.Ala12Thr), gnomAD 5-128083988-G-A, REVEL 0.27, CADD 14.80
- A12S (p.Ala12Ser), gnomAD 5-128083988-G-T, REVEL 0.22, CADD 14.90
- A12A (p.Ala12Ala), gnomAD 5-128083990-C-A, CADD 7.13
- P13L (p.Pro13Leu), TOPMed rs1759927661, REVEL 0.21, CADD 3.35
- P13R (p.Pro13Arg), gnomAD 5-128083988-GC-G, CADD 18.20
- P13T (p.Pro13Thr), gnomAD 5-128083991-C-A, REVEL 0.24, CADD 8.69
- P13S (p.Pro13Ser), gnomAD 5-128083991-C-T, REVEL 0.21, CADD 8.62
- P13A (p.Pro13Ala), gnomAD 5-128083991-C-G, REVEL 0.23, CADD 3.17
- P13Q (p.Pro13Gln), gnomAD 5-128083992-C-A, REVEL 0.25, CADD 4.42
- P13P (p.Pro13Pro), gnomAD 5-128083993-G-T, CADD 6.62
- G14R (p.Gly14Arg), TOPMed rs1759927937, gnomAD rs1759927937, REVEL 0.25, CADD 7.38
- G14V (p.Gly14Val), rs1014756958, ClinGen CA126980063, ClinVar RCV001907848, ClinVar RCV002506912, REVEL 0.22, CADD 15.70, Uncertain significance, Inborn genetic diseases; Kilquist syndrome; Hearing loss, autosomal dominant 78
- G14D (p.Gly14Asp), gnomAD 5-128083992-CG-C, CADD 17.30
- G14* (p.Gly14Ter), gnomAD 5-128083994-G-T, CADD 27.40
- G14E (p.Gly14Glu), gnomAD 5-128083995-G-A, REVEL 0.25, CADD 16.00
- G14G (p.Gly14Gly), gnomAD 5-128083996-A-G, CADD 8.90
- L15T (p.Leu15Thr), gnomAD 5-128083988-G-GC, CADD 23.10
- L15M (p.Leu15Met), gnomAD 5-128083997-C-A, REVEL 0.21, CADD 8.72
- L15V (p.Leu15Val), gnomAD 5-128083997-C-G, REVEL 0.24, CADD 5.87
- L15L (p.Leu15Leu), gnomAD 5-128083997-C-T, CADD 5.79
- L15P (p.Leu15Pro), gnomAD 5-128083998-T-C, REVEL 0.29, CADD 10.80
- L15Q (p.Leu15Gln), gnomAD 5-128083998-T-A, REVEL 0.34, CADD 8.91
- A16S (p.Ala16Ser), gnomAD 5-128084000-G-T, REVEL 0.16, CADD 15.10
- A16T (p.Ala16Thr), gnomAD 5-128084000-G-A, REVEL 0.18, CADD 17.20
- A16D (p.Ala16Asp), gnomAD 5-128084001-C-A, REVEL 0.40, CADD 11.50
- A16V (p.Ala16Val), gnomAD 5-128084001-C-T, REVEL 0.18, CADD 10.90
- A16G (p.Ala16Gly), gnomAD 5-128084001-C-G, REVEL 0.21, CADD 9.26
- A16A (p.Ala16Ala), gnomAD 5-128084002-C-G, CADD 7.21
- G17R (p.Gly17Arg), Ensembl rs1581037245, REVEL 0.17, CADD 9.05
- G17V (p.Gly17Val), TOPMed rs1759928715, REVEL 0.15, CADD 12.70
- G17W (p.Gly17Trp), gnomAD 5-128084003-G-T, REVEL 0.32, CADD 16.70
- G17A (p.Gly17Ala), gnomAD 5-128084004-G-C, REVEL 0.15, CADD 6.80
- G17E (p.Gly17Glu), gnomAD 5-128084004-G-A, REVEL 0.20, CADD 16.40
- G17G (p.Gly17Gly), gnomAD 5-128084005-G-C, CADD 7.46
- V18F (p.Val18Phe), rs1025704186, ClinGen CA126980083, ClinVar RCV003084270, ClinVar RCV003269445, REVEL 0.25, CADD 11.20, Uncertain significance, Inborn genetic diseases; not provided
- V18I (p.Val18Ile), TOPMed rs1025704186, gnomAD rs1025704186, REVEL 0.23, CADD 8.29, Uncertain significance
- V18S (p.Val18Ser), gnomAD 5-128084000-GC-G, CADD 18.40
- V18A (p.Val18Ala), gnomAD 5-128084007-T-C, REVEL 0.20, CADD 5.14
- V18V (p.Val18Val), gnomAD 5-128084008-C-A, CADD 5.67
- G19R (p.Gly19Arg), gnomAD 5-128084009-G-C, REVEL 0.20, CADD 22.50
- G19W (p.Gly19Trp), gnomAD 5-128084009-G-T, REVEL 0.22, CADD 24.40
- G19V (p.Gly19Val), gnomAD 5-128084010-G-T, REVEL 0.16, CADD 18.60
- G19E (p.Gly19Glu), gnomAD 5-128084010-G-A, REVEL 0.24, CADD 14.90
- G19G (p.Gly19Gly), gnomAD 5-128084011-G-T, CADD 8.76
- E20G (p.Glu20Gly), Ensembl rs2126627598, REVEL 0.28, CADD 18.50
- E20K (p.Glu20Lys), Ensembl rs1383164404, REVEL 0.24, CADD 17.10
- E20R (p.Glu20Arg), gnomAD 5-128084008-CG-C, CADD 23.80
- E20* (p.Glu20Ter), gnomAD 5-128084012-G-T, CADD 35.00
- E20Q (p.Glu20Gln), gnomAD 5-128084012-G-C, REVEL 0.32, CADD 16.40
- E20V (p.Glu20Val), gnomAD 5-128084013-A-T, REVEL 0.22, CADD 19.40
- E20E (p.Glu20Glu), gnomAD 5-128084014-G-A, CADD 8.07
- E20D (p.Glu20Asp), gnomAD 5-128084014-G-T, REVEL 0.29, CADD 13.30
- T21A (p.Thr21Ala), Ensembl rs1170331876, REVEL 0.31, CADD 19.40
- T21M (p.Thr21Met), gnomAD 5-128084016-C-T, REVEL 0.28, CADD 20.60
- T21K (p.Thr21Lys), gnomAD 5-128084016-C-A, REVEL 0.25, CADD 20.30
- T21T (p.Thr21Thr), gnomAD 5-128084017-G-A, CADD 8.34
- P22L (p.Pro22Leu), TOPMed rs1759930298, REVEL 0.22, CADD 16.50
- P22S (p.Pro22Ser), rs1759930102, ClinGen CA360735734, ClinVar RCV004456230, ClinVar RCV005065113, REVEL 0.19, CADD 16.70, Uncertain significance, not provided; Inborn genetic diseases
- P22T (p.Pro22Thr), gnomAD 5-128084018-C-A, REVEL 0.18, CADD 19.50
- P22A (p.Pro22Ala), gnomAD 5-128084018-C-G, REVEL 0.21, CADD 15.30
- P22Q (p.Pro22Gln), gnomAD 5-128084019-C-A, REVEL 0.19, CADD 11.40
- P22R (p.Pro22Arg), gnomAD 5-128084019-C-G, REVEL 0.19, CADD 15.90
- P22P (p.Pro22Pro), gnomAD 5-128084020-G-T, CADD 5.63
- S23L (p.Ser23Leu), TOPMed rs1759930491, REVEL 0.22, CADD 8.38
- S23Q (p.Ser23Gln), gnomAD 5-128084019-CG-C, CADD 16.20
- S23P (p.Ser23Pro), gnomAD 5-128084021-T-C, REVEL 0.22, CADD 7.42
- S23* (p.Ser23Ter), gnomAD 5-128084022-C-A, CADD 29.60
- S23S (p.Ser23Ser), gnomAD 5-128084023-A-T, CADD 4.71
- A24S (p.Ala24Ser), gnomAD 5-128084024-G-T, REVEL 0.10, CADD 14.90
- A24P (p.Ala24Pro), gnomAD 5-128084024-G-C, REVEL 0.09, CADD 16.40
- A24T (p.Ala24Thr), gnomAD 5-128084024-G-A, REVEL 0.09, CADD 16.10
- A24G (p.Ala24Gly), gnomAD 5-128084025-C-G, REVEL 0.11, CADD 15.20
- A24D (p.Ala24Asp), gnomAD 5-128084025-C-A, REVEL 0.08, CADD 15.50
- A24V (p.Ala24Val), gnomAD 5-128084025-C-T, REVEL 0.09, CADD 15.50
- A24A (p.Ala24Ala), gnomAD 5-128084026-C-A, CADD 6.45
- A25T (p.Ala25Thr), gnomAD rs1310186988, REVEL 0.10, CADD 10.60
- A25P (p.Ala25Pro), gnomAD 5-128084027-G-C, REVEL 0.11, CADD 11.20
- A25S (p.Ala25Ser), gnomAD 5-128084027-G-T, REVEL 0.10, CADD 6.85
- A25D (p.Ala25Asp), gnomAD 5-128084028-C-A, REVEL 0.12, CADD 2.96
- A25V (p.Ala25Val), gnomAD 5-128084028-C-T, REVEL 0.12, CADD 8.75
- A25A (p.Ala25Ala), gnomAD 5-128084029-T-C, CADD 7.84
- A26T (p.Ala26Thr), TOPMed rs1449986853, gnomAD rs1449986853, REVEL 0.14, CADD 14.70
- A26V (p.Ala26Val), Ensembl rs1759931261, REVEL 0.20, CADD 15.80, Uncertain significance, not provided
- A26S (p.Ala26Ser), gnomAD 5-128084030-G-T, REVEL 0.16, CADD 13.30
- A26E (p.Ala26Glu), gnomAD 5-128084031-C-A, REVEL 0.21, CADD 15.30
- A26G (p.Ala26Gly), gnomAD 5-128084031-C-G, REVEL 0.13, CADD 15.70
- A26A (p.Ala26Ala), gnomAD 5-128084032-G-A, CADD 6.23
- L27V (p.Leu27Val), TOPMed rs1185970616, REVEL 0.17, CADD 6.79
- L27L (p.Leu27Leu), gnomAD 5-128084033-C-T, CADD 6.26
- L27M (p.Leu27Met), gnomAD 5-128084033-C-A, REVEL 0.22, CADD 8.62
- L27Q (p.Leu27Gln), gnomAD 5-128084034-T-A, REVEL 0.22, CADD 12.10
- L27P (p.Leu27Pro), gnomAD 5-128084034-T-C, REVEL 0.17, CADD 11.90
- A28V (p.Ala28Val), TOPMed rs1759932009, REVEL 0.20, CADD 14.70
- A28P (p.Ala28Pro), gnomAD 5-128084036-G-C, REVEL 0.20, CADD 16.50
- A28S (p.Ala28Ser), gnomAD 5-128084036-G-T, REVEL 0.21, CADD 10.60
- A28T (p.Ala28Thr), gnomAD 5-128084036-G-A, REVEL 0.17, CADD 12.10
- A28G (p.Ala28Gly), gnomAD 5-128084037-C-G, REVEL 0.18, CADD 14.50
- A28D (p.Ala28Asp), gnomAD 5-128084037-C-A, REVEL 0.22, CADD 18.00
- A28A (p.Ala28Ala), gnomAD 5-128084038-C-A, CADD 6.51
- A29T (p.Ala29Thr), gnomAD rs1242333495, REVEL 0.19, CADD 11.80
- A29S (p.Ala29Ser), gnomAD 5-128084039-G-T, REVEL 0.15, CADD 8.95
- A29P (p.Ala29Pro), gnomAD 5-128084039-G-C, REVEL 0.13, CADD 11.80
- A29V (p.Ala29Val), gnomAD 5-128084040-C-T, REVEL 0.12, CADD 15.10
- A29E (p.Ala29Glu), gnomAD 5-128084040-C-A, REVEL 0.15, CADD 14.60
- A29G (p.Ala29Gly), gnomAD 5-128084040-C-G, REVEL 0.12, CADD 14.00
- A29A (p.Ala29Ala), rs994939943, gnomAD 5-128084041-A-C, CADD 9.03
- A30G (p.Ala30Gly), ExAC rs761637816, TOPMed rs761637816, gnomAD rs761637816, REVEL 0.09, CADD 16.10
- A30S (p.Ala30Ser), gnomAD 5-128084042-G-T, REVEL 0.21, CADD 14.90
- A30P (p.Ala30Pro), gnomAD 5-128084042-G-C, REVEL 0.31, CADD 21.10
- A30T (p.Ala30Thr), gnomAD 5-128084042-G-A, REVEL 0.22, CADD 15.90
- A30D (p.Ala30Asp), gnomAD 5-128084043-C-A, REVEL 0.37, CADD 22.90
Public SLC12A2 analysis runs
- SLC12A2 analysis run — SLC12A2 (1,754 variants) — completed 2026-08-20