Human Gene SCN9A (ENST00000409672.5)
  Description: Homo sapiens sodium voltage-gated channel alpha subunit 9 (SCN9A), transcript variant 1, mRNA. (from RefSeq NM_002977)
RefSeq Summary (NM_002977): 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: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Gencode Transcript: ENST00000409672.5
Gencode Gene: ENSG00000169432.18
Transcript (Including UTRs)
   Position: hg38 chr2:166,195,185-166,375,993 Size: 180,809 Total Exon Count: 27 Strand: -
Coding Region
   Position: hg38 chr2:166,198,672-166,311,756 Size: 113,085 Coding Exon Count: 26 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:166,195,185-166,375,993)mRNA (may differ from genome)Protein (1977 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGImyGene2neXtProtOMIM
PubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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";

-  MalaCards Disease Associations
  MalaCards Gene Search: SCN9A
Diseases sorted by gene-association score: paroxysmal extreme pain disorder* (1703), insensitivity to pain, congenital* (1675), erythermalgia, primary* (1650), febrile seizures, familial, 3b* (1330), erythromelalgia* (791), epileptic encephalopathy, early infantile, 6* (418), sodium channelopathy-related small fiber neuropathy* (350), neuropathy, hereditary sensory and autonomic, type v* (283), neuropathy, hereditary sensory and autonomic, type ii* (175), scn9a-related inherited erythromelalgia* (100), scn9a-related dravet syndrome* (100), scn9a-related generalized epilepsy with febrile seizures plus* (100), pain disorder (57), generalized epilepsy with febrile seizures plus* (25), trigeminal neuralgia (23), burning mouth syndrome (17), febrile seizures (16), genetic epilepsy with febrile seizures plus (13), complex regional pain syndrome (8), autonomic dysfunction (7), trigeminal nerve disease (6), diabetic neuropathy (5), hyperekplexia (5), somatoform disorder (5), autosomal dominant disease (2), peripheral nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 4.39 RPKM in Brain - Hypothalamus
Total median expression: 38.05 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -149.80347-0.432 Picture PostScript Text
3' UTR -760.903487-0.218 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR024583 - DUF3451
IPR005821 - Ion_trans_dom
IPR000048 - IQ_motif_EF-hand-BS
IPR001696 - Na_channel_asu
IPR010526 - Na_trans_assoc

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  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

Cellular Component:
GO:0001518 voltage-gated sodium channel complex
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0042995 cell projection


-  Descriptions from all associated GenBank mRNAs
  X82835 - H.sapiens mRNA for voltage-activated sodium channel.
BC113079 - Homo sapiens cDNA clone IMAGE:40071234.
BC113080 - Homo sapiens cDNA clone IMAGE:40071236.
DQ857292 - Homo sapiens voltage-gated sodium channel Nav1.7 (SCN9A) mRNA, complete cds.
AK307549 - Homo sapiens cDNA, FLJ97497.
JD459753 - Sequence 440777 from Patent EP1572962.
JD329303 - Sequence 310327 from Patent EP1572962.
AJ277393 - Homo sapiens partial mRNA for voltage-gated sodium channel (SCN9A gene), 3'UTR.
JD245643 - Sequence 226667 from Patent EP1572962.
AJ310897 - Homo sapiens partial mRNA for voltage-gated sodium Nav1.7 (SCN9A gene) (SCN9A gene), cell line MDA-MB-231.
JD025850 - Sequence 6874 from Patent EP1572962.
JD028844 - Sequence 9868 from Patent EP1572962.
AY682084 - Homo sapiens voltage-gated sodium channel Nav1.7 (SCN9A) mRNA, partial cds, alternatively spliced.
AY682085 - Homo sapiens voltage-gated sodium channel Nav1.7 (SCN9A) mRNA, partial cds, alternatively spliced.
AY682086 - Homo sapiens voltage-gated sodium channel Nav1.7 (SCN9A) mRNA, partial cds, alternatively spliced.
AJ310882 - Homo sapiens partial mRNA for voltage-gated sodium channel Nav1.7 (SCN9A gene), D1 neonatal splice variant, cell line MDA-MB-231.
AJ310883 - Homo sapiens partial mRNA for Nav1.7 voltage-gated-sodium channel (SCN9A gene), D1 neonatal splice variant, cell line MCF-7.
JD309111 - Sequence 290135 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q15858 (Reactome details) participates in the following event(s):

R-HSA-373739 Ankyrins link voltage-gated sodium and potassium channels to spectrin and L1
R-HSA-5576895 SCNAs:SNCBs transport Na+ from extracellular region to cytosol
R-HSA-445095 Interaction between L1 and Ankyrins
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-373760 L1CAM interactions
R-HSA-5576891 Cardiac conduction
R-HSA-422475 Axon guidance
R-HSA-397014 Muscle contraction
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: A1BUH5, ENST00000409672.1, ENST00000409672.2, ENST00000409672.3, ENST00000409672.4, NENA, NM_002977, Q15858, Q6B4R9, Q6B4S0, Q6B4S1, Q70HX1, Q70HX2, Q8WTU1, Q8WWN4, SCN9A_HUMAN, uc010fpl.1, uc010fpl.2, uc010fpl.3, uc010fpl.4
UCSC ID: ENST00000409672.5
RefSeq Accession: NM_002977
Protein: Q15858 (aka SCN9A_HUMAN)
CCDS: CCDS46441.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SCN9A:
hsan2 (Hereditary Sensory and Autonomic Neuropathy Type II)
etha (SCN9A Neuropathic Pain Syndromes)
cip-overview (Congenital Insensitivity to Pain Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.