SCN7A

Chr 2

sodium voltage-gated channel alpha subunit 7

Also known as: NaG, Nav2.1, Nav2.2, SCN6A

This protein functions as a sodium leak channel that acts as an osmosensor, regulating sodium ion levels across tissues including glial cells in the central nervous system and keratinocytes in skin barrier homeostasis. The gene is extremely intolerant to loss-of-function variants, but no human diseases have been definitively associated with SCN7A mutations to date. The inheritance pattern for any potential SCN7A-related disorders remains to be established.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.78
Clinical SummarySCN7A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.95
OE 0.60 (0.460.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.41Z-score
OE missense 0.96 (0.901.02)
761 obs / 793.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.460.78)
00.351.4
Missense OE0.96 (0.901.02)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 37 / 62.1Missense obs/exp: 761 / 793.3Syn Z: -0.59
DN
0.78top 25%
GOF
0.77top 25%
LOF
0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SCN7A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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