SLC12A7

Chr 5

solute carrier family 12 member 7

The SLC12A7 protein mediates electroneutral potassium-chloride cotransport and is important for potassium recycling in the inner ear and chloride handling in the kidney. Mutations cause autosomal recessive sensorineural hearing loss with or without renal tubular acidosis. This gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.89
Clinical SummarySLC12A7
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Gene-Disease Validity (ClinGen)
renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss · UDNo Known Disease Relationship

No known disease relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 2.23
OE 0.67 (0.510.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.32Z-score
OE missense 0.86 (0.810.92)
622 obs / 722.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.510.89)
00.351.4
Missense OE0.86 (0.810.92)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 35 / 52.4Missense obs/exp: 622 / 722.0Syn Z: -3.05
DN
0.7325th %ile
GOF
0.82top 10%
LOF
0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC12A7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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