SCNN1B
Chr 16ADARsodium channel epithelial 1 subunit beta
Also known as: BESC1, ENaCb, ENaCbeta, LIDLS1, PHA1B2, SCNEB, beta-ENaC, beta-NaCH
The SCNN1B gene encodes the beta subunit of the epithelial sodium channel (ENaC), which controls sodium and fluid transport across epithelial tissues in the kidneys, lungs, and other organs. Mutations cause pseudohypoaldosteronism type 1 (autosomal recessive) presenting with severe salt wasting and dehydration in infancy, or Liddle syndrome (autosomal dominant) characterized by early-onset hypertension and hypokalemia. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance being possible for complete loss of function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 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 | 10 | 1 | 9 | 0 | 20 |
Likely Pathogenic | 16 | 6 | 1 | 0 | 23 |
VUS | 3 | 194 | 18 | 4 | 219 |
Likely Benign | 0 | 7 | 33 | 34 | 74 |
Benign | 0 | 0 | 31 | 0 | 31 |
Conflicting | — | 25 | |||
| Total | 29 | 208 | 92 | 38 | 392 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCNN1B · 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
External Resources
Links to major genomics databases and tools