SLC4A7
Chr 3solute carrier family 4 member 7
Also known as: NBC2, NBC3, NBCN1, SBC2, SLC4A6
The sodium bicarbonate cotransporter encoded by this gene transports sodium and bicarbonate ions in a 1:1 ratio to regulate intracellular pH, particularly important for visual and auditory sensory transmission, macrophage function, and cellular nucleotide synthesis. Mutations cause autosomal recessive retinal dystrophy with early-onset hearing loss and intellectual disability. This gene is highly constrained against loss-of-function variants (LOEUF 0.34), indicating that such mutations are likely to have significant clinical consequences.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). 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.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
173 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 16 | 0 | 16 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 105 | 5 | 0 | 110 |
Likely Benign | 0 | 4 | 3 | 7 | 14 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 109 | 25 | 7 | 141 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC4A7 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools