SCNN1G
Chr 16ADARsodium channel epithelial 1 subunit gamma
Also known as: BESC3, ENaCg, ENaCgamma, LDLS2, PHA1, PHA1B3, SCNEG
The protein forms the gamma subunit of the epithelial sodium channel (ENaC), which mediates sodium reabsorption in the kidneys and maintains airway surface liquid homeostasis for proper mucus clearance. Mutations cause Liddle syndrome, pseudohypoaldosteronism type IB3, and bronchiectasis with or without elevated sweat chloride, with both autosomal dominant and autosomal recessive inheritance patterns depending on the condition. The gene is moderately constrained against loss-of-function variants (LOEUF 0.408), reflecting its essential role in sodium and fluid homeostasis across multiple organ systems.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
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
391 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 | 8 | 0 | 26 | 0 | 34 |
Likely Pathogenic | 8 | 0 | 3 | 0 | 11 |
VUS | 1 | 161 | 27 | 9 | 198 |
Likely Benign | 0 | 4 | 32 | 34 | 70 |
Benign | 0 | 1 | 44 | 5 | 50 |
Conflicting | — | 23 | |||
| Total | 17 | 166 | 132 | 48 | 386 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCNN1G · 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