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GeneBe

SCN10A

sodium voltage-gated channel alpha subunit 10, the group of Sodium voltage-gated channel alpha subunits

Basic information

Region (hg38): 3:38696801-38816286

Links

ENSG00000185313NCBI:6336OMIM:604427HGNC:10582Uniprot:Q9Y5Y9AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Brugada syndrome (Limited), mode of inheritance: Unknown
  • episodic pain syndrome, familial, 2 (Limited), mode of inheritance: AD
  • episodic pain syndrome, familial, 2 (No Known Disease Relationship), mode of inheritance: AD
  • sodium channelopathy-related small fiber neuropathy (Supportive), mode of inheritance: AD
  • Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD
  • episodic pain syndrome, familial, 2 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Episodic pain syndrome, familial, 2ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic23115331

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN10A gene.

  • Brugada syndrome (1150 variants)
  • Cardiovascular phenotype (1022 variants)
  • not provided (425 variants)
  • Episodic pain syndrome, familial, 2 (119 variants)
  • not specified (105 variants)
  • Inborn genetic diseases (39 variants)
  • Brugada syndrome 1 (14 variants)
  • SCN10A-related condition (3 variants)
  • Sodium channelopathy-related small fiber neuropathy (1 variants)
  • - (1 variants)
  • See cases (1 variants)
  • Impaired temperature sensation (1 variants)
  • SCN10A-Related Disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN10A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
13
clinvar
388
clinvar
10
clinvar
411
missense
825
clinvar
71
clinvar
4
clinvar
900
nonsense
34
clinvar
34
start loss
1
clinvar
1
frameshift
42
clinvar
42
inframe indel
1
clinvar
10
clinvar
1
clinvar
12
splice donor/acceptor (+/-2bp)
17
clinvar
17
splice region
30
31
1
62
non coding
4
clinvar
125
clinvar
54
clinvar
183
Total 0 1 946 585 68

Variants in SCN10A

This is a list of pathogenic ClinVar variants found in the SCN10A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
3-38697226-G-A Benign (Jun 19, 2018)1259657
3-38697302-C-T Likely benign (Jul 27, 2018)1187276
3-38697354-G-T Brugada syndrome • Cardiovascular phenotype Uncertain significance (Jun 04, 2022)463270
3-38697357-C-T Brugada syndrome Uncertain significance (Jun 15, 2022)2413826
3-38697362-G-A Brugada syndrome • Cardiovascular phenotype Uncertain significance (Oct 12, 2021)852767
3-38697362-G-C Cardiovascular phenotype Uncertain significance (May 06, 2023)2563719
3-38697364-A-G Brugada syndrome Likely benign (May 27, 2022)1986433
3-38697367-C-A Brugada syndrome Likely benign (Mar 17, 2023)3011837
3-38697369-G-A Brugada syndrome Likely benign (Dec 31, 2023)2820556
3-38697374-A-T Cardiovascular phenotype Likely benign (Jan 05, 2022)1750038
3-38697382-G-A Brugada syndrome Likely benign (Nov 01, 2022)1115595
3-38697386-T-C not specified • Brugada syndrome • Cardiovascular phenotype Benign/Likely benign (Dec 08, 2023)391439
3-38697393-C-A Brugada syndrome Uncertain significance (Jul 23, 2020)968400
3-38697400-T-C Brugada syndrome • Cardiovascular phenotype Conflicting classifications of pathogenicity (Mar 13, 2023)834159
3-38697403-T-G Brugada syndrome Likely benign (May 17, 2021)1659246
3-38697411-A-G Cardiovascular phenotype Uncertain significance (Dec 18, 2022)2448840
3-38697416-C-T Cardiovascular phenotype • Brugada syndrome Uncertain significance (Feb 06, 2022)1749801
3-38697428-C-CT Brugada syndrome Uncertain significance (Jun 21, 2021)1362938
3-38697431-T-A Brugada syndrome • Cardiovascular phenotype Likely benign (Aug 22, 2022)757184
3-38697432-C-T Brugada syndrome Uncertain significance (Mar 15, 2023)2803475
3-38697439-G-A Brugada syndrome Likely benign (Dec 09, 2018)789421
3-38697439-G-T Cardiovascular phenotype Likely benign (Dec 16, 2021)1749613
3-38697441-C-T Cardiovascular phenotype Uncertain significance (Jan 06, 2020)1749588
3-38697445-A-C Cardiovascular phenotype Likely benign (Jan 19, 2022)1749575
3-38697446-G-A Cardiovascular phenotype Uncertain significance (Oct 29, 2021)1749569

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCN10Aprotein_codingprotein_codingENST00000449082 2797209
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
9.95e-380.0010012549302551257480.00101
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.68211441.08e+31.060.000061212933
Missense in Polyphen421436.110.965365427
Synonymous-1.934654151.120.00002393820
Loss of Function1.446578.80.8250.00000437902

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001920.00192
Ashkenazi Jewish0.0004960.000496
East Asian0.002120.00212
Finnish0.0002780.000277
European (Non-Finnish)0.0009890.000985
Middle Eastern0.002120.00212
South Asian0.0008870.000882
Other0.001790.00179

dbNSFP

Source: dbNSFP

Function
FUNCTION: 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. {ECO:0000269|PubMed:9839820}.;
Disease
DISEASE: Episodic pain syndrome, familial, 2 (FEPS2) [MIM:615551]: An autosomal dominant neurologic disorder characterized by adult- onset of paroxysmal pain mainly affecting the distal lower extremities. {ECO:0000269|PubMed:23115331}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Lidocaine (Local Anaesthetic) Metabolism Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

pRec
0.0970

Intolerance Scores

loftool
0.0382
rvis_EVS
-1.32
rvis_percentile_EVS
4.74

Haploinsufficiency Scores

pHI
0.190
hipred
Y
hipred_score
0.520
ghis
0.462

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.205

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scn10a
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);

Gene ontology

Biological process
regulation of heart rate;sensory perception;neuronal action potential;sensory perception of pain;regulation of ion transmembrane transport;sodium ion transmembrane transport;odontogenesis of dentin-containing tooth;regulation of cardiac muscle contraction;regulation of atrial cardiac muscle cell membrane depolarization;membrane depolarization during action potential;AV node cell action potential;bundle of His cell action potential
Cellular component
voltage-gated sodium channel complex;plasma membrane;axon;extracellular exosome;clathrin complex;glutamatergic synapse;integral component of presynaptic membrane
Molecular function
voltage-gated ion channel activity;voltage-gated sodium channel activity;ion channel binding