SCN11A sodium voltage-gated channel alpha subunit 11 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SCN11Aprovided by HGNC
Official Full Name: sodium voltage-gated channel alpha subunit 11provided by HGNC
Primary source: HGNC:HGNC:10583
See related: Ensembl:ENSG00000168356 MIM:604385; AllianceGenome:HGNC:10583
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NaN; PN5; FEPS3; HSAN7; SNS-2; NAV1.9; SCN12A
Summary: Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is highly expressed in nociceptive neurons of dorsal root ganglia and trigeminal ganglia. It mediates brain-derived neurotrophic factor-evoked membrane depolarization and is a major effector of peripheral inflammatory pain hypersensitivity. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy type VII and familial episodic pain syndrome-3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]
Expression: Biased expression in spleen (RPKM 1.9), placenta (RPKM 0.6) and 13 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p22.2

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (38845764..39051944, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (38857981..39064106, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (38887255..39093435, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.
Title: The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.
Understanding the physiological role of NaV1.9: Challenges and opportunities for pain modulation.
Title: Understanding the physiological role of Na(V)1.9: Challenges and opportunities for pain modulation.
Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons.
Title: Contributions of Na(V)1.8 and Na(V)1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons.
Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.
Title: Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.
Alcohol-aggravated episodic pain in humans with SCN11A mutation and ALDH2 polymorphism.
Title: Alcohol-aggravated episodic pain in humans with SCN11A mutation and ALDH2 polymorphism.
A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane.
Title: A 49-residue sequence motif in the C terminus of Nav1.9 regulates trafficking of the channel to the plasma membrane.
Findings suggest that higher PBMC SCN11A expression levels may be associated with certain behavioral bipolar disorder (BD) sub-phenotypes, including lack of alcohol dependence and psychosis, among BD patients.
Title: SCN11A mRNA levels in female bipolar disorder PBMCs as tentative biomarker for distinct patient sub-phenotypes.
The frequency of (potentially) pathogenic variants was 5.1% (n=58/1139) for SCN9A, 3.7% (n=42/1139) for SCN10A and 2.9% (n=33/1139) for SCN11A in pure small fibre neuropathy.
Title: Yield of peripheral sodium channels gene screening in pure small fibre neuropathy.
data suggest an important contribution of NaV1.9 to itch signaling.
Title: A disease mutation reveals a role for NaV1.9 in acute itch.
A total of 11 mutations in SCN11A: p.R222H in seven families, and p.R225C, p.F814C, p.F1146S, or p.V1184A, in independent families. A founder mutation, SCN11A p.R222H was confirmed to be frequently observed in patients with Familial episodic limb pain in Japan. And identification of two novel missense variants of SCN11A, p.F814C and p.F1146S.
Title: Familial episodic limb pain in kindreds with novel Nav1.9 mutations.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Familial episodic pain syndrome with predominantly lower limb involvement MedGen: C3809899 OMIM: 615552 GeneReviews: Not available	Compare labs
Hereditary sensory and autonomic neuropathy type 7 MedGen: C3809882 OMIM: 615548 GeneReviews: Congenital Insensitivity to Pain Overview	Compare labs

EBI GWAS Catalog

Description
Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S275 (e-PCR)
- UniSTS:147992

D8S2279 (e-PCR)
- UniSTS:473907

L18426 (e-PCR)
- UniSTS:34648

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables voltage-gated sodium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated sodium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in action potential initiation	IEA Inferred from Electronic Annotation more info
involved_in acute inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in artery development	IEA Inferred from Electronic Annotation more info
involved_in axonogenesis	IEA Inferred from Electronic Annotation more info
involved_in behavioral response to acetic acid induced pain	IEA Inferred from Electronic Annotation more info
involved_in behavioral response to formalin induced pain	IEA Inferred from Electronic Annotation more info
involved_in calcitonin gene-related peptide receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in cardiac muscle cell action potential involved in contraction	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell motility	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cold	IEA Inferred from Electronic Annotation more info
involved_in chronic inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in detection of mechanical stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in detection of temperature stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in mast cell degranulation	IEA Inferred from Electronic Annotation more info
involved_in membrane depolarization during action potential	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane depolarization during action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in micturition	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in protein kinase A signaling	IEA Inferred from Electronic Annotation more info
involved_in reflex	IEA Inferred from Electronic Annotation more info
involved_in response to auditory stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to heat	IEA Inferred from Electronic Annotation more info
involved_in response to high light intensity	IEA Inferred from Electronic Annotation more info
involved_in response to nitric oxide	IEA Inferred from Electronic Annotation more info
involved_in response to prostaglandin E	IEA Inferred from Electronic Annotation more info
involved_in response to toxic substance	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of itch	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of pain	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sensory perception of pain	ISS Inferred from Sequence or Structural Similarity more info
involved_in skeletal muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in small intestine smooth muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in thermosensory behavior	IEA Inferred from Electronic Annotation more info
involved_in thigmotaxis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in C-fiber	IEA Inferred from Electronic Annotation more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in axonal growth cone	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
part_of voltage-gated sodium channel complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: sodium channel protein type 11 subunit alpha

Names: peripheral nerve sodium channel 5; sensory neuron sodium channel 2; sodium channel protein type XI subunit alpha; sodium channel, voltage-gated, type XI, alpha polypeptide; sodium channel, voltage-gated, type XI, alpha subunit; sodium channel, voltage-gated, type XII, alpha polypeptide; voltage-gated sodium channel subunit alpha Nav1.9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033859.2 RefSeqGene

Range

5043..211223

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001349253.2 → NP_001336182.1 sodium channel protein type 11 subunit alpha

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC116038, AC123903

Consensus CDS

CCDS33737.1

UniProtKB/Swiss-Prot

A6NN05, C9JD48, C9JR31, Q68K15, Q8NDX3, Q9UHE0, Q9UHM0, Q9UI33

UniProtKB/TrEMBL

A0A6Q8PGN4

Related

ENSP00000307599.3, ENST00000302328.9

Conserved Domains (4) summary

cd13433
Location:1309 → 1361

Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits

pfam00520
Location:1055 → 1317

Ion_trans; Ion transport protein

pfam06512
Location:828 → 1051

Na_trans_assoc; Sodium ion transport-associated

pfam16905
Location:1618 → 1678

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_014139.3 → NP_054858.2 sodium channel protein type 11 subunit alpha

See identical proteins and their annotated locations for NP_054858.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC116038, AC123903

Consensus CDS

CCDS33737.1

UniProtKB/Swiss-Prot

A6NN05, C9JD48, C9JR31, Q68K15, Q8NDX3, Q9UHE0, Q9UHM0, Q9UI33

UniProtKB/TrEMBL

A0A6Q8PGN4

Related

ENSP00000416757.3, ENST00000456224.7

Conserved Domains (4) summary

cd13433
Location:1309 → 1361

Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits

pfam00520
Location:1055 → 1317

Ion_trans; Ion transport protein

pfam06512
Location:828 → 1051

Na_trans_assoc; Sodium ion transport-associated

pfam16905
Location:1618 → 1678

GPHH; Voltage-dependent L-type calcium channel, IQ-associated

RNA

NR_164473.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC123903

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

38845764..39051944 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047447378.1 → XP_047303334.1 sodium channel protein type 11 subunit alpha isoform X1
XM_017005650.2 → XP_016861139.1 sodium channel protein type 11 subunit alpha isoform X2

UniProtKB/Swiss-Prot

A6NN05, C9JD48, C9JR31, Q68K15, Q8NDX3, Q9UHE0, Q9UHM0, Q9UI33

UniProtKB/TrEMBL

A0A6Q8PGN4

Conserved Domains (4) summary

cd13433
Location:1309 → 1361

Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits

pfam00520
Location:1055 → 1317

Ion_trans; Ion transport protein

pfam06512
Location:828 → 1051

Na_trans_assoc; Sodium ion transport-associated

pfam16905
Location:1618 → 1678

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
XM_017005651.2 → XP_016861140.1 sodium channel protein type 11 subunit alpha isoform X3

UniProtKB/TrEMBL

A0A6Q8PGN4
XM_011533321.3 → XP_011531623.1 sodium channel protein type 11 subunit alpha isoform X4

UniProtKB/TrEMBL

A0A6Q8PGN4

Conserved Domains (5) summary

cd13433
Location:1088 → 1140

Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits

pfam00520
Location:1162 → 1394

Ion_trans; Ion transport protein

pfam06512
Location:607 → 830

Na_trans_assoc; Sodium ion transport-associated

pfam16905
Location:1403 → 1457

GPHH; Voltage-dependent L-type calcium channel, IQ-associated

cl21478
Location:159 → 214

ATP-synt_B; ATP synthase B/B' CF(0)
XM_017005653.2 → XP_016861142.1 sodium channel protein type 11 subunit alpha isoform X5

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

38857981..39064106 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054345105.1 → XP_054201080.1 sodium channel protein type 11 subunit alpha isoform X1
XM_054345106.1 → XP_054201081.1 sodium channel protein type 11 subunit alpha isoform X2

UniProtKB/Swiss-Prot

A6NN05, C9JD48, C9JR31, Q68K15, Q8NDX3, Q9UHE0, Q9UHM0, Q9UI33
XM_054345107.1 → XP_054201082.1 sodium channel protein type 11 subunit alpha isoform X3
XM_054345108.1 → XP_054201083.1 sodium channel protein type 11 subunit alpha isoform X4
XM_054345109.1 → XP_054201084.1 sodium channel protein type 11 subunit alpha isoform X5