SCN10A

Chr 3AD

sodium voltage-gated channel alpha subunit 10

NCBI Gene: 6336ENSG00000185313UniProt: Q9Y5Y9

Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms

Primary Disease Associations & Inheritance

Episodic pain syndrome, familial, 2MIM #615551
AD
2590
ClinVar variants
2
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SCN10A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 Pathogenic / Likely Pathogenic· 316 VUS of 2590 total submissions

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.
1.01LOEUF
pLI 0.000
Z-score 1.44
OE 0.82 (0.67–1.01)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.68Z-score
OE missense 1.06 (1.01–1.11)
1144 obs / 1080.9 exp
Tolerant

Tolerant to missense variation

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.0.82 (0.67–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (1.01–1.11)
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.1.12
0≤1.21.6
LoF obs/exp: 65 / 78.8Missense obs/exp: 1144 / 1080.9Syn Z: -1.93

ClinVar Variant Classifications

2590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS316
Likely Benign180
1
Pathogenic
1
Likely Pathogenic
316
VUS
180
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
1
0
0
1
VUS
19
276
18
3
316
Likely Benign
0
7
64
109
180
Benign
0
0
0
0
0
Total1928483112498

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

View in ClinVar →

Protein Context — Lollipop Plot

SCN10A · protein map & ClinVar variants

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

Gene2Phenotype Curations

SCN10A-related Brugada syndrome

disputed
ADUndeterminedUncertain
Cardiac
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Episodic pain syndrome, familial, 2

MIM #615551

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Erythromelalgia.
Klein-Weigel PF et al.·Vasa
2018Review
The Evolving Landscape of Small Fiber Neuropathy.
Devigili G et al.·Semin Neurol
2025Review
Small fibre neuropathy.
Cazzato D et al.·Curr Opin Neurol
2017Review
The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.
Al-Kasbi G et al.·Sci Rep
2022
Genetic Analysis of SCN11A, SCN10A, and SCN9A in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria.
Noguchi A et al.·Int J Mol Sci
2024
Genome-Wide Association Study of Accessory Atrioventricular Pathways.
Aegisdottir HM et al.·JAMA Cardiol
2024
The impact of common and rare genetic variants on bradyarrhythmia development.
Weng LC et al.·Nat Genet
2025
Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.
Xie YF·Biomolecules
2025Review
Inherited progressive cardiac conduction disorders.
Baruteau AE et al.·Curr Opin Cardiol
2015Review
Genetic Variants and Clinical Phenotyping in 39 Pediatric Patients with Neuropathic Pain.
Quade A et al.·Neuropediatrics
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Effect of pain-related sodium channels SCN9A and SCN10A polymorphisms in migraine chronification.
Kilic E et al.·Neurol Res
2025
SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias.
Wang J et al.·Eur Heart J
2025
SCN10A gene polymorphism is associated with pain sensitivity and postoperative analgesic effects in patients undergoing gynecological laparoscopy.
Gao Y et al.·Eur J Med Res
2025🔓 Open AccessCohort
A Multidisciplinary Approach to Navigating Variants of Uncertain Significance in Sudden Infant Deaths: A Case Report of 2 Siblings With an SCN10A VUS.
Dumm R et al.·Am J Forensic Med Pathol
2025Case report
Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.
Coates MD et al.·Clin Transl Gastroenterol
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools