SLC4A4
Chr 4ARsolute carrier family 4 member 4
Also known as: HNBC1, KNBC, NBC1, NBC2, NBCe1, NBCe1-A, PRTAO, SLC4A5
This gene encodes an electrogenic sodium/bicarbonate cotransporter that regulates bicarbonate transport across cell membranes and maintains intracellular pH. Mutations cause proximal renal tubular acidosis with ocular anomalies, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
ClinVar Variant Classifications
417 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 | 4 | 2 | 19 | 0 | 25 |
Likely Pathogenic | 6 | 4 | 1 | 0 | 11 |
VUS | 1 | 152 | 55 | 9 | 217 |
Likely Benign | 1 | 2 | 40 | 55 | 98 |
Benign | 0 | 2 | 18 | 4 | 24 |
Conflicting | — | 19 | |||
| Total | 12 | 162 | 133 | 68 | 394 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC4A4 · 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