View source for SCN2A

{{cs1 config|name-list-style=vanc}}
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{DISPLAYTITLE:SCN2A}}
{{Infobox_gene}}
'''Sodium channel protein type 2 subunit alpha''', is a [[protein]] that in humans is encoded by the ''SCN2A'' [[gene]].<ref name="entrez"/>  Functional [[sodium channel]]s contain an ion conductive alpha subunit and one or more regulatory beta subunits.  Sodium channels which contain sodium channel protein type 2 subunit alpha are sometimes called '''Na<sub>v</sub>1.2''' channels.
== Function ==
[[Sodium channel#Voltage-gated|Voltage-gated sodium channel]]s are transmembrane [[glycoprotein]] complexes composed of a large alpha subunit with four domains including 24 transmembrane segments and one or more regulatory beta subunits. They are responsible for the generation and propagation of [[action potential]]s in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is heterogeneously expressed in the brain, and mutations in this gene have been linked to several [[seizure]] disorders. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.<ref name="entrez">{{cite web | title = Entrez Gene: SCN2A sodium channel, voltage-gated, type II, alpha subunit| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6326}}</ref>
== Clinical significance ==
Mutations in this gene have been implicated in cases of [[autism]],<ref name=Murtha_2012>{{cite journal|last=Sanders SJ|first=Stephan J.|author2=Murtha MT |author3=Gupta AR |author4=Murdoch JR |author5=Raubeson MJ |author6=Willsey AJ |author7=Ercan-Sencicek AG | title = De novo mutations revealed by whole-exome sequencing are strongly associated with autism | journal = Nature | year = 2012 | doi = 10.1038/nature10945 |pmid=22495306|display-authors=etal | volume=485 |issue=7397| pages=237–241|pmc=3667984 |bibcode=2012Natur.485..237S}}</ref> [[infantile spasm]]s, bitemporal glucose hypometabolism,<ref name="pmid23827426">{{cite journal |vauthors=Sundaram SK, Chugani HT, Tiwari VN, Huq AH | title = SCN2A Mutation Is Associated With Infantile Spasms and Bitemporal Glucose Hypometabolism | journal = Pediatr. Neurol. | volume = 49 | issue = 1 | pages = 46–9 |date=July 2013 | pmid = 23827426 | doi = 10.1016/j.pediatrneurol.2013.03.002 | pmc=3868437}}</ref> and [[bipolar disorder]].<ref name = Stahl_2019>{{cite journal|last=Bipolar Disorder Working Group of the Psychiatric Genomics Consortium| title = Genome-wide association study identifies 30 loci associated with bipolar disorder | journal = Nature Genetics | year = 2019 | doi = 10.1038/s41588-019-0397-8 |pmid= 31043756 |display-authors=etal | volume=51 | issue = 5 | pages=793–803| hdl= 10481/58017 | hdl-access= free | pmc= 6956732 }}</ref>
==See also==
* [[Paralytic (gene)|''paralytic'']] - SCN2A ortholog in ''Drosophila''
==References==
{{reflist}}
==Further reading==
{{refbegin | 2}}
*{{cite journal  |vauthors=Catterall WA, Goldin AL, Waxman SG |title=International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. |journal=Pharmacol. Rev. |volume=57 |issue= 4 |pages= 397–409 |year= 2006 |pmid= 16382098 |doi= 10.1124/pr.57.4.4 |s2cid=7332624 |url=https://semanticscholar.org/paper/2e6f7e97c54bc8cd20f0c9a6efb0deb6f5b5e20b }}
*{{cite journal  |vauthors=Lu CM, Han J, Rado TA, Brown GB |title=Differential expression of two sodium channel subtypes in human brain. |journal=FEBS Lett. |volume=303 |issue= 1 |pages= 53–8 |year= 1992 |pmid= 1317301 |doi=10.1016/0014-5793(92)80476-W  |s2cid=29330026 }}
*{{cite journal   |vauthors=Ahmed CM, Ware DH, Lee SC, etal |title=Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 17 |pages= 8220–4 |year= 1992 |pmid= 1325650 |doi=10.1073/pnas.89.17.8220  | pmc=49889  |bibcode=1992PNAS...89.8220A |doi-access=free }}
*{{cite journal  |vauthors=Han JA, Lu CM, Brown GB, Rado TA |title=Direct amplification of a single dissected chromosomal segment by polymerase chain reaction: a human brain sodium channel gene is on chromosome 2q22-q23 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 2 |pages= 335–9 |year= 1991 |pmid= 1846440 |doi=10.1073/pnas.88.2.335  | pmc=50805  |bibcode=1991PNAS...88..335H |doi-access=free }}
*{{cite journal   |vauthors=Litt M, Luty J, Kwak M, etal |title=Localization of a human brain sodium channel gene (SCN2A) to chromosome 2 |journal=Genomics |volume=5 |issue= 2 |pages= 204–8 |year= 1989 |pmid= 2571571 |doi=10.1016/0888-7543(89)90047-5  }}
*{{cite journal  |vauthors=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791  |doi-access=free }}
*{{cite journal   |vauthors=Lu CM, Eichelberger JS, Beckman ML, etal |title=Isolation of the 5'-flanking region for human brain sodium channel subtype II alpha-subunit |journal=J. Mol. Neurosci. |volume=11 |issue= 3 |pages= 179–82 |year= 1999 |pmid= 10344788 |doi=10.1385/JMN:11:3:179  |s2cid=33328638 }}
*{{cite journal   |vauthors=Baulac S, Gourfinkel-An I, Picard F, etal |title=A Second Locus for Familial Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2q21-q33 |journal=Am. J. Hum. Genet. |volume=65 |issue= 4 |pages= 1078–85 |year= 2000 |pmid= 10486327 |doi=10.1086/302593  | pmc=1288241  }}
*{{cite journal  |vauthors=Schade SD, Brown GB |title=Identifying the promoter region of the human brain sodium channel subtype II gene (SCN2A) |journal=Brain Res. Mol. Brain Res. |volume=81 |issue= 1–2 |pages= 187–90 |year= 2001 |pmid= 11000491 |doi=10.1016/S0169-328X(00)00145-5  }}
*{{cite journal   |vauthors=Kasai N, Fukushima K, Ueki Y, etal |title=Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the DFNA16 locus |journal=Gene |volume=264 |issue= 1 |pages= 113–22 |year= 2001 |pmid= 11245985 |doi=10.1016/S0378-1119(00)00594-1  }}
*{{cite journal   |vauthors=Malacarne M, Gennaro E, Madia F, etal |title=Benign Familial Infantile Convulsions: Mapping of a Novel Locus on Chromosome 2q24 and Evidence for Genetic Heterogeneity |journal=Am. J. Hum. Genet. |volume=68 |issue= 6 |pages= 1521–6 |year= 2001 |pmid= 11326335 |doi=10.1086/320596  | pmc=1226140  }}
*{{cite journal   |vauthors=Sugawara T, Tsurubuchi Y, Agarwala KL, etal |title=A missense mutation of the Na+ channel αII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 11 |pages= 6384–9 |year= 2001 |pmid= 11371648 |doi= 10.1073/pnas.111065098  | pmc=33477 |bibcode=2001PNAS...98.6384S |doi-access=free }}
*{{cite journal   |vauthors=Heron SE, Crossland KM, Andermann E, etal |title=Sodium-channel defects in benign familial neonatal-infantile seizures |journal=Lancet |volume=360 |issue= 9336 |pages= 851–2 |year= 2002 |pmid= 12243921 |doi=10.1016/S0140-6736(02)09968-3  |s2cid=6105850 }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal   |vauthors=Weiss LA, Escayg A, Kearney JA, etal |title=Sodium channels SCN1A, SCN2A and SCN3A in familial autism |journal=Mol. Psychiatry |volume=8 |issue= 2 |pages= 186–94 |year= 2003 |pmid= 12610651 |doi= 10.1038/sj.mp.4001241 |s2cid=16606651 |doi-access=  }}
*{{cite journal   |vauthors=Yu FH, Westenbroek RE, Silos-Santiago I, etal |title=Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2 |journal=J. Neurosci. |volume=23 |issue= 20 |pages= 7577–85 |year= 2003 |pmid= 12930796 |pmc=6740763 |doi=  10.1523/JNEUROSCI.23-20-07577.2003}}
*{{cite journal   |vauthors=McEwen DP, Meadows LS, Chen C, etal |title=Sodium channel beta1 subunit-mediated modulation of Nav1.2 currents and cell surface density is dependent on interactions with contactin and ankyrin |journal=J. Biol. Chem. |volume=279 |issue= 16 |pages= 16044–9 |year= 2004 |pmid= 14761957 |doi= 10.1074/jbc.M400856200 |doi-access= free }}
*{{cite journal   |vauthors=Kamiya K, Kaneda M, Sugawara T, etal |title=A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline |journal=J. Neurosci. |volume=24 |issue= 11 |pages= 2690–8 |year= 2004 |pmid= 15028761 |pmc=6729532 |doi= 10.1523/JNEUROSCI.3089-03.2004 }}
*{{cite journal   |vauthors=Berkovic SF, Heron SE, Giordano L, etal |title=Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy |journal=Ann. Neurol. |volume=55 |issue= 4 |pages= 550–7 |year= 2004 |pmid= 15048894 |doi= 10.1002/ana.20029 |s2cid=11604421 }}
*{{cite journal   |vauthors=Pereira S, Vieira JP, Barroca F, etal |title=Severe epilepsy, retardation, and dysmorphic features with a 2q deletion including SCN1A and SCN2A |journal=Neurology |volume=63 |issue= 1 |pages= 191–2 |year= 2004 |pmid= 15249644 |doi=  10.1212/01.wnl.0000132844.20654.c1|s2cid=38453487 }}
{{refend}}
== External links ==
Patient Organizations
[https://www.scn2afoundation.org/ The SCN2A Foundation]
[https://scn2aaustralia.org SCN2A Asia Pacific]
[https://scn2a.de SCN2A Germany e. V.]
* {{MeshName|SCN2A+protein,+human}}
* {{PDBe-KB2|Q99250|Sodium channel protein type 2 subunit alpha}}
{{PDB Gallery|geneid=6326}}
{{Ion channels|g2}}
{{NLM content}}
[[Category:Sodium channels]]
{{membrane-protein-stub}}