SCN7A

Chr 2

sodium voltage-gated channel alpha subunit 7

ENSG00000136546UniProt: Q01118

Sodium leak channel functioning as an osmosensor regulating sodium ion levels in various tissues and organs. While most sodium channels are voltage-gated, SCN7A is not and lets sodium flow through membrane along its concentration gradient (PubMed:26537257, PubMed:35301303). In glial cells of the central nervous system, senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake through activation of nearby neurons to maintain appropriate sodium levels in the body (By similarity). By mediating sodium influx into keratinocytes, also plays a role in skin barrier homeostasis (PubMed:26537257)

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SCN7A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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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.
0.78LOEUF
pLI 0.000
Z-score 2.95
OE 0.60 (0.46–0.78)
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.
0.41Z-score
OE missense 0.96 (0.90–1.02)
761 obs / 793.3 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.0.60 (0.46–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.90–1.02)
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.1.05
0≤1.21.6
LoF obs/exp: 37 / 62.1Missense obs/exp: 761 / 793.3Syn Z: -0.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer.
Li W et al.·BMC Gastroenterol
2022
Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies.
Almomani R et al.·Int J Mol Sci
2023
Germline mutations in young non-smoking women with lung adenocarcinoma.
Donner I et al.·Lung Cancer
2018
[A comprehensive analysis of potential prognostic biomarkers for MYCN-amplified neuroblastoma].
Fan X et al.·Zhongguo Dang Dai Er Ke Za Zhi
2020
Concurrent sodium channelopathies and amyotrophic lateral sclerosis supports shared pathogenesis.
Franklin JP et al.·Amyotroph Lateral Scler Frontotemporal Degener
2020
Fusobacterium nucleatum predicts a high risk of metastasis for esophageal squamous cell carcinoma.
Li Z et al.·BMC Microbiol
2021
Genetic testing after sudden death with negative ancillary investigations: A French prospective study with multidisciplinary collaboration.
Osouf J et al.·Forensic Sci Int Genet
2026
Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy.
Ślęczkowska M et al.·Int J Mol Sci
2022
Methylation- and homologous recombination deficiency-related mutant genes predict the prognosis of lung adenocarcinoma.
Nie GJ et al.·J Clin Lab Anal
2022
Whole-genome sequencing reveals the impact of lipid pathway and APOE genotype on brain amyloidosis.
Patel M et al.·Hum Mol Genet
2025
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

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools