SCNN1G

Chr 16

sodium channel epithelial 1 subunit gamma

Also known as: BESC3, ENaCg, ENaCgamma, LDLS2, PHA1, PHA1B3, SCNEG

NCBI Gene: 6340 ENSG00000166828 UniProt: P51170

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.

ResearchSummary from RefSeq, OMIM, 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 gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.41

Clinical Summary— SCNN1G

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Gene-Disease Validity (ClinGen)

Liddle syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.482

Z-score 4.12

OE 0.22 (0.12–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.56Z-score

OE missense 0.92 (0.84–1.00)

328 obs / 357.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.12–0.41)

0≤0.351.4

Missense OE?0.92 (0.84–1.00)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 7 / 32.2Missense obs/exp: 328 / 357.9Syn Z: -0.49

This gene — mechanism propensity

0.5576th %ile

GOF

0.5955th %ile

LOF

0.3356th %ile

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

GOF1 literature citation

Literature Evidence

GOFLiddle syndrome is an autosomal dominant genetic condition that causes hypertension and hypokalemia due to a gain-of-function mutation in the SCNN1B or SCNN1G genes which code for the epithelial sodium channel in the kidney.1

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

References