SCNN1B

Chr 16ADAR

sodium channel epithelial 1 subunit beta

Also known as: BESC1, ENaCb, ENaCbeta, LIDLS1, PHA1B2, SCNEB, beta-ENaC, beta-NaCH

NCBI Gene: 6338 ENSG00000168447 UniProt: P51168 OMIM: 600760

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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome. [provided by RefSeq, Apr 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 0.803 OMIM phenotypes

Clinical Summary— SCNN1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

48 unique Pathogenic / Likely Pathogenic· 237 VUS of 467 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SCNN1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.45

OE 0.53 (0.36–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.21Z-score

OE missense 0.97 (0.89–1.06)

362 obs / 373.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.36–0.80)

0≤0.351.4

Missense OE?0.97 (0.89–1.06)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 17 / 32.0Missense obs/exp: 362 / 373.5Syn Z: -0.87

This gene — mechanism propensity

0.6744th %ile

GOF

0.72top 25%

LOF

0.1895th %ile

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.

GOFprediction above median · 1 literature citation

DNprediction 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.

Literature Evidence

GOFGain-of-function mutations in ENaC beta and gamma subunits cause pseudoaldosteronism (Liddle's syndrome), a severe form of salt-sensitive hypertension.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 11826291 ↗

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic29

VUS237

Likely Benign93

Benign36

Conflicting46

Pathogenic

Likely Pathogenic

237

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	4	1	0	19
Likely Pathogenic	20	9	0	0	29
VUS	3	207	21	6	237
Likely Benign	0	11	37	45	93
Benign	0	2	32	2	36
Conflicting	—				46
Total	37	233	91	53	460

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap SCNN1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →