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GeneBe

SCN11A

sodium voltage-gated channel alpha subunit 11, the group of Sodium voltage-gated channel alpha subunits

Basic information

Region (hg38): 3:38845763-39052157

Previous symbols: [ "SCN12A" ]

Links

ENSG00000168356NCBI:11280OMIM:604385HGNC:10583Uniprot:Q9UI33AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • sodium channelopathy-related small fiber neuropathy (Supportive), mode of inheritance: AD
  • familial episodic pain syndrome with predominantly lower limb involvement (Supportive), mode of inheritance: AD
  • hereditary sensory and autonomic neuropathy type 7 (Supportive), mode of inheritance: AD
  • autosomal dominant hereditary sensory and autonomic neuropathy (Definitive), mode of inheritance: AD
  • familial episodic pain syndrome with predominantly lower limb involvement (Definitive), mode of inheritance: AD
  • familial episodic pain syndrome with predominantly lower limb involvement (Strong), mode of inheritance: AD
  • hereditary sensory and autonomic neuropathy type 7 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Episodic pain syndrome, familial, 3; Neuropathy, hereditary sensory and autonomic, type VIIADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic24036948; 24207120; 24776970; 25118027
The pain has been reported as responsive to oral anti-inflammatory analgesics; Congenital insensitivity to pain can result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN11A gene.

  • Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement (749 variants)
  • not provided (263 variants)
  • Inborn genetic diseases (249 variants)
  • Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 (198 variants)
  • not specified (21 variants)
  • Hereditary sensory and autonomic neuropathy type 7 (15 variants)
  • Familial episodic pain syndrome with predominantly lower limb involvement (14 variants)
  • Charcot-Marie-Tooth disease (6 variants)
  • SCN11A-related condition (2 variants)
  • See cases (1 variants)
  • Congenital sensory neuropathy with selective loss of small myelinated fibers (1 variants)
  • Sensory neuropathy (1 variants)
  • Hereditary motor neuron disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN11A 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
10
clinvar
197
clinvar
15
clinvar
222
missense
4
clinvar
2
clinvar
550
clinvar
45
clinvar
4
clinvar
605
nonsense
1
clinvar
26
clinvar
27
start loss
0
frameshift
30
clinvar
30
inframe indel
14
clinvar
14
splice donor/acceptor (+/-2bp)
16
clinvar
16
splice region
19
23
1
43
non coding
1
clinvar
108
clinvar
72
clinvar
181
Total 4 3 647 350 91

Highest pathogenic variant AF is 0.0000131

Variants in SCN11A

This is a list of pathogenic ClinVar variants found in the SCN11A region.

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

Position Type Phenotype Significance ClinVar
3-38846479-T-A Benign (Jul 05, 2018)1273152
3-38846530-T-C Benign (Jul 05, 2018)1178114
3-38846594-G-T Likely benign (Sep 22, 2018)1201052
3-38846699-C-G Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Nov 01, 2023)2951554
3-38846702-A-G Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Uncertain significance (Oct 13, 2023)1402950
3-38846704-T-C Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Jan 17, 2024)2942969
3-38846711-T-C Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement • Inborn genetic diseases Conflicting classifications of pathogenicity (Sep 06, 2023)474749
3-38846712-G-A Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Uncertain significance (Mar 25, 2020)1058787
3-38846713-C-T Inborn genetic diseases Uncertain significance (Sep 01, 2022)1747031
3-38846724-C-T Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Likely benign (Aug 23, 2021)1100366
3-38846729-A-T Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Jul 16, 2023)2953021
3-38846736-C-T Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Benign (Feb 01, 2024)474748
3-38846744-C-G Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Nov 17, 2023)2949801
3-38846749-CAA-C Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (May 30, 2023)2946220
3-38846750-A-G Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Dec 30, 2023)2935086
3-38846758-T-C Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement • Inborn genetic diseases Uncertain significance (Oct 28, 2022)541558
3-38846759-G-A Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Uncertain significance (Nov 04, 2022)2142189
3-38846761-A-G Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Apr 05, 2023)2941732
3-38846764-G-A Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Oct 23, 2023)641428
3-38846771-G-A Inborn genetic diseases Uncertain significance (Jun 06, 2023)2557053
3-38846778-G-A Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Likely benign (Nov 03, 2020)763550
3-38846788-T-C Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Uncertain significance (Aug 28, 2022)1718213
3-38846788-T-G Familial episodic pain syndrome with predominantly lower limb involvement;Hereditary sensory and autonomic neuropathy type 7 Uncertain significance (Nov 03, 2022)2941264
3-38846790-A-T Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement • Inborn genetic diseases Benign/Likely benign (Dec 15, 2023)703369
3-38846791-T-C Hereditary sensory and autonomic neuropathy type 7;Familial episodic pain syndrome with predominantly lower limb involvement Uncertain significance (May 18, 2022)2080654

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCN11Aprotein_codingprotein_codingENST00000302328 26104793
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
6.93e-260.96112551702311257480.000919
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9648819650.9130.000051711927
Missense in Polyphen324422.060.767655339
Synonymous-0.2493503441.020.00001863317
Loss of Function2.845380.50.6590.00000451933

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002640.00264
Ashkenazi Jewish0.0001990.000198
East Asian0.0003890.000381
Finnish0.0006010.000601
European (Non-Finnish)0.001090.000976
Middle Eastern0.0003890.000381
South Asian0.0008510.000588
Other0.001170.00114

dbNSFP

Source: dbNSFP

Function
FUNCTION: This protein 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. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization. {ECO:0000269|PubMed:10580103, ECO:0000269|PubMed:12384689}.;
Disease
DISEASE: Neuropathy, hereditary sensory and autonomic, 7 (HSAN7) [MIM:615548]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN7 is characterized by congenital inability to experience pain resulting in self-mutilations, slow-healing wounds, and multiple painless fractures. mild muscle weakness, delayed motor development, slightly reduced motor and sensory nerve conduction velocities, hyperhidrosis and gastrointestinal dysfunction. {ECO:0000269|PubMed:24036948, ECO:0000269|PubMed:26645915}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Episodic pain syndrome, familial, 3 (FEPS3) [MIM:615552]: An autosomal dominant neurologic disorder characterized by paroxysmal pain mainly affecting the distal lower extremities and occasionally the upper body, especially the joints of fingers and arms. The pain is exacerbated with fatigue. {ECO:0000269|PubMed:24207120, ECO:0000269|PubMed:24776970, ECO:0000269|PubMed:25791876, ECO:0000269|PubMed:27224030}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Intolerance Scores

loftool
0.0774
rvis_EVS
-1.82
rvis_percentile_EVS
2.14

Haploinsufficiency Scores

pHI
0.0474
hipred
N
hipred_score
0.233
ghis
0.409

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.135

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scn11a
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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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
sodium ion transport;neuronal action potential;regulation of ion transmembrane transport;sodium ion transmembrane transport;response to drug;regulation of sensory perception of pain;membrane depolarization during action potential
Cellular component
voltage-gated sodium channel complex;plasma membrane;axon;C-fiber;extracellular exosome
Molecular function
voltage-gated ion channel activity;voltage-gated sodium channel activity