Human Gene SCN9A (ENST00000642356.2) from GENCODE V44
Description: Homo sapiens sodium voltage-gated channel alpha subunit 9 (SCN9A), transcript variant 2, mRNA. (from RefSeq NM_001365536) RefSeq Summary (NM_001365536): This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]. Sequence Note: The RefSeq transcript and protein were derived from genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments. Gencode Transcript: ENST00000642356.2 Gencode Gene: ENSG00000169432.19 Transcript (Including UTRs) Position: hg38 chr2:166,195,185-166,375,944 Size: 180,760 Total Exon Count: 27 Strand: - Coding Region Position: hg38 chr2:166,198,672-166,311,756 Size: 113,085 Coding Exon Count: 26
ID:SCN9A_HUMAN DESCRIPTION: RecName: Full=Sodium channel protein type 9 subunit alpha; AltName: Full=Neuroendocrine sodium channel; Short=hNE-Na; AltName: Full=Peripheral sodium channel 1; Short=PN1; AltName: Full=Sodium channel protein type IX subunit alpha; AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.7; FUNCTION: 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 Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity). SUBUNIT: The sodium channel consists of a large polypeptide and 2- 3 smaller ones. This sequence represents a large polypeptide. Interacts with NEDD4 and NEDD4L (By similarity). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Note=In neurite terminals (By similarity). TISSUE SPECIFICITY: Expressed strongly in dorsal root ganglion, with only minor levels elsewhere in the body, smooth muscle cells, MTC cell line and C-cell carcinoma. Isoform 1 is expressed preferentially in the central and peripheral nervous system. Isoform 2 is expressed preferentially in the dorsal root ganglion. DOMAIN: The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position. PTM: Ubiquitinated by NEDD4L; which may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4 (By similarity). DISEASE: Defects in SCN9A are the cause of primary erythermalgia (PERYTHM) [MIM:133020]. It is an autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. DISEASE: Defects in SCN9A are the cause of congenital indifference to pain autosomal recessive (CIPAR) [MIM:243000]; also known as channelopathy-associated insensitivity to pain. A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating. DISEASE: Defects in SCN9A are a cause of paroxysmal extreme pain disorder (PEPD) [MIM:167400]; previously known as familial rectal pain (FRP). PEPD is an autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing. DISEASE: Defects in SCN9A are a cause of generalized epilepsy with febrile seizures plus type 7 (GEFS+7) [MIM:613863]. GEFS+7 is a rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. DISEASE: Defects in SCN9A are the cause of familial febrile convulsions type 3B (FEB3B) [MIM:613863]. FEB3B consists of seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.7/SCN9A subfamily. SIMILARITY: Contains 1 IQ domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN9A"; WEB RESOURCE: Name=Wikipedia; Note=SCN9A entry; URL="http://en.wikipedia.org/wiki/SCN9A"; WEB RESOURCE: Name=Protein Spotlight; Note=Silent pain - Issue 102 of February 2009; URL="http://web.expasy.org/spotlight/back_issues/sptlt102.shtml";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF11933 - Cytoplasmic domain of voltage-gated Na+ ion channel PF00520 - Ion transport protein PF06512 - Sodium ion transport-associated
ModBase Predicted Comparative 3D Structure on Q15858
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0005248 voltage-gated sodium channel activity GO:0005272 sodium channel activity GO:0031402 sodium ion binding
Biological Process: GO:0006811 ion transport GO:0006814 sodium ion transport GO:0006954 inflammatory response GO:0009636 response to toxic substance GO:0009791 post-embryonic development GO:0019228 neuronal action potential GO:0019233 sensory perception of pain GO:0034765 regulation of ion transmembrane transport GO:0035725 sodium ion transmembrane transport GO:0048266 behavioral response to pain GO:0055085 transmembrane transport GO:0086010 membrane depolarization during action potential
GeneReviews article(s) related to gene SCN9A: cip-overview (Congenital Insensitivity to Pain Overview) etha (SCN9A Neuropathic Pain Syndromes) hsan2 (Hereditary Sensory and Autonomic Neuropathy Type II)
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