SCNN1B

Chr 16ADAR

sodium channel epithelial 1 subunit beta

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

NCBI Gene: 6338ENSG00000168447UniProt: P51168

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]

Primary Disease Associations & Inheritance

Bronchiectasis with or without elevated sweat chloride 1MIM #211400
AD
Liddle syndrome 1MIM #177200
AD
Pseudohypoaldosteronism, type IB2, autosomal recessiveMIM #620125
AR
502
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SCNN1B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 Pathogenic / Likely Pathogenic· 171 VUS of 502 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 2.45
OE 0.53 (0.36–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.21Z-score
OE missense 0.97 (0.89–1.06)
362 obs / 373.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.53 (0.36–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.89–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 17 / 32.0Missense obs/exp: 362 / 373.5Syn Z: -0.87

ClinVar Variant Classifications

502 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic20
VUS171
Likely Benign81
Benign36
Conflicting42
44
Pathogenic
20
Likely Pathogenic
171
VUS
81
Likely Benign
36
Benign
42
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
4
33
0
44
Likely Pathogenic
6
8
6
0
20
VUS
3
139
25
4
171
Likely Benign
0
10
33
38
81
Benign
0
2
32
2
36
Conflicting
—42
Total1616312944394

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bronchiectasis with or without elevated sweat chloride 1

MIM #211400

Molecular basis of disorder known

Autosomal dominant

Liddle syndrome 1

MIM #177200

Molecular basis of disorder known

Autosomal dominant

Pseudohypoaldosteronism, type IB2, autosomal recessive

MIM #620125

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteomics and tubulopathies.
Vilasi A et al.·J Nephrol
2010Review
Clinical Management in Systemic Type Pseudohypoaldosteronism Due to SCNN1B Variant and Literature Review.
Karacan Küçükali G et al.·J Clin Res Pediatr Endocrinol
2021Review
Liddle syndrome with a SCNN1B mutation: a case report and systematic review.
Tang Q et al.·BMC Nephrol
2025Case report
A frameshift mutation in the SCNN1B gene in a family with Liddle syndrome: A case report and systematic review.
Lu Y et al.·Mol Med Rep
2024Case report
Epithelial Sodium and Chloride Channels and Asthma.
Wang W et al.·Chin Med J (Engl)
2015Review
Reverse Phenotypes of Patients with Genetically Confirmed Liddle Syndrome.
Granhøj J et al.·Clin J Am Soc Nephrol
2024Cohort
Germline targeted next-generation sequencing in patients with adrenal incidentalomas.
Messina E et al.·Front Endocrinol (Lausanne)
2025Cohort
Scnn1b-Transgenic BALB/c Mice as a Model of Pseudomonas aeruginosa Infections of the Cystic Fibrosis Lung.
Brao KJ et al.·Infect Immun
2020Functional
Sodium Channel Subunit SCNN1B Suppresses Gastric Cancer Growth and Metastasis via GRP78 Degradation.
Qian Y et al.·Cancer Res
2017
Phenotypic diversity and correlation with the genotypes of pseudohypoaldosteronism type 1.
Gopal-Kothandapani JS et al.·J Pediatr Endocrinol Metab
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Adenine Phosphoribosyltransferase DeficiencyAH AmyloidosisAHL Amyloidosis

National Registry of Rare Kidney Diseases

RECRUITING
NCT06065852UK Kidney AssociationStarted 2009-11-06

External Resources

Links to major genomics databases and tools