SCN10A

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

Basic information

Region (hg38): 3:38696802-38816286

Links

ENSG00000185313 ∙ NCBI:6336 ∙ OMIM:604427 ∙ HGNC:10582 ∙ Uniprot:Q9Y5Y9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• episodic pain syndrome, familial, 2 (Limited), mode of inheritance: AD
• Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Episodic pain syndrome, familial, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23115331

ClinVar

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

• Cardiovascular_phenotype (1502 variants)
• Brugada_syndrome (1331 variants)
• not_provided (484 variants)
• not_specified (138 variants)
• Episodic_pain_syndrome,_familial,_2 (120 variants)
• SCN10A-related_disorder (58 variants)
• Brugada_syndrome_1 (14 variants)
• Autism (1 variants)
• Impaired_temperature_sensation (1 variants)
• Hereditary_sodium_channelopathy-related_small_fibers_neuropathy (1 variants)
• Congenital_long_QT_syndrome (1 variants)
• See_cases (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. These statistics are base on transcript: NM_000006514.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	560	2	574
missense			1118	221	1	1340
nonsense			46	4		50
start loss			1			1
frameshift			57	2		59
splice donor/acceptor (+/-2bp)			21	3		24
Total	0	0	1255	790	3

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCN10A	protein_coding	protein_coding	ENST00000449082	27	97209

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.95e-38	0.00100	125493	0	255	125748	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.682	1144	1.08e+3	1.06	0.0000612	12933
Missense in Polyphen		421	436.11	0.96536		5427
Synonymous	-1.93	465	415	1.12	0.0000239	3820
Loss of Function	1.44	65	78.8	0.825	0.00000437	902

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00192	0.00192
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.00212	0.00212
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000989	0.000985
Middle Eastern	0.00212	0.00212
South Asian	0.000887	0.000882
Other	0.00179	0.00179

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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