SCNN1D

Chr 1

sodium channel epithelial 1 subunit delta

Also known as: ENaCd, ENaCdelta, SCNED, dNaCh

NCBI Gene: 6339ENSG00000162572UniProt: P51172

The protein functions as an alternative pore-forming subunit of the epithelial sodium channel (ENaC), replacing the alpha subunit to create a more active channel that regulates sodium balance and fluid homeostasis across epithelial tissues. Mutations cause pseudohypoaldosteronism type 1, which presents with severe salt wasting, dehydration, and failure to thrive in infancy, following autosomal recessive inheritance. The gene shows no constraint against loss-of-function variants, consistent with the recessive disease pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
137
P/LP submissions
0%
P/LP missense
1.59
LOEUF
GOF
Mechanism· predicted
Clinical Summary— SCNN1D
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
130 unique Pathogenic / Likely Pathogenic· 205 VUS of 408 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.59LOEUF
pLI 0.000
Z-score -1.33
OE 1.24 (0.97–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.78Z-score
OE missense 1.10 (1.02–1.18)
526 obs / 477.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.24 (0.97–1.59)
0≤0.351.4
Missense OE1.10 (1.02–1.18)
0≤0.61.4
Synonymous OE1.34
0≤1.21.6
LoF obs/exp: 45 / 36.4Missense obs/exp: 526 / 477.9Syn Z: -3.99
DN
0.5476th %ile
GOF
0.6639th %ile
LOF
0.4332th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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

408 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic123
Likely Pathogenic7
VUS205
Likely Benign45
Benign2
123
Pathogenic
7
Likely Pathogenic
205
VUS
45
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
123
0
123
Likely Pathogenic
0
0
7
0
7
VUS
0
188
17
0
205
Likely Benign
0
34
2
9
45
Benign
0
0
1
1
2
Total022215010382

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SCNN1D · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The evolutionary path of the epithelial sodium channel delta-subunit in Cetartiodactyla points to a role in sodium sensing
Zahnow F et al.·Commun Biol
2025
The evolutionary path of the epithelial sodium channel delta-subunit in Cetartiodactyla points to a role in sodium sensing
Zahnow F et al.·bioRxiv
2024
Transgenically expressed human delta epithelial sodium channel facilitated fluid absorption in mouse fetal lung explants.
Jain KG et al.·Am J Physiol Lung Cell Mol Physiol
2025Functional
Two Functional Epithelial Sodium Channel Isoforms Are Present in Rodents despite Pronounced Evolutionary Pseudogenization and Exon Fusion
Gettings SM et al.·Mol Biol Evol
2021Functional
Rare variants in genes encoding subunits of the epithelial Na+ channel are associated with blood pressure and kidney function
Blobner BM et al.·Hypertension
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients