SLC26A4
Chr 7ARsolute carrier family 26 member 4
Also known as: DFNB4, EVA, PDS, TDH2B
The encoded protein is a sodium-independent transporter that mediates electroneutral exchange of chloride and iodide, as well as chloride-bicarbonate exchange. Mutations cause Pendred syndrome, the most common form of syndromic deafness, which follows autosomal recessive inheritance and typically involves both hearing loss and thyroid dysfunction. This gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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.
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
300 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 | 42 | 8 | 4 | 0 | 54 |
Likely Pathogenic | 35 | 50 | 4 | 1 | 90 |
VUS | 1 | 108 | 11 | 8 | 128 |
Likely Benign | 0 | 1 | 13 | 9 | 23 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 78 | 167 | 32 | 18 | 296 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC26A4 · 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
Cohort Of DEafness-gene Screening
ACTIVE NOT RECRUITINGRole of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism With in Situ Thyroid
RECRUITINGExternal Resources
Links to major genomics databases and tools