SCN2A explained

Sodium channel protein type 2 subunit alpha, is a protein that in humans is encoded by the SCN2A gene. Functional sodium channels 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_v1.2 channels.

Function

Voltage-gated sodium channels 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 potentials 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.^[1]

Clinical significance

Mutations in this gene have been implicated in cases of autism,^[2] infantile spasms, bitemporal glucose hypometabolism,^[3] and bipolar disorder.^[4]

See also

• paralytic - SCN2A ortholog in Drosophila

Further reading

• Catterall WA, Goldin AL, Waxman SG . International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. . Pharmacol. Rev. . 57 . 4 . 397–409 . 2006 . 16382098 . 10.1124/pr.57.4.4 . 7332624 .
• Lu CM, Han J, Rado TA, Brown GB . Differential expression of two sodium channel subtypes in human brain. . FEBS Lett. . 303 . 1 . 53–8 . 1992 . 1317301 . 10.1016/0014-5793(92)80476-W . 29330026 .
• Ahmed CM, Ware DH, Lee SC, etal . Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain . Proc. Natl. Acad. Sci. U.S.A. . 89 . 17 . 8220–4 . 1992 . 1325650 . 10.1073/pnas.89.17.8220 . 49889 . 1992PNAS...89.8220A . free .
• Han JA, Lu CM, Brown GB, Rado TA . Direct amplification of a single dissected chromosomal segment by polymerase chain reaction: a human brain sodium channel gene is on chromosome 2q22-q23 . Proc. Natl. Acad. Sci. U.S.A. . 88 . 2 . 335–9 . 1991 . 1846440 . 10.1073/pnas.88.2.335 . 50805 . 1991PNAS...88..335H . free .
• Litt M, Luty J, Kwak M, etal . Localization of a human brain sodium channel gene (SCN2A) to chromosome 2 . Genomics . 5 . 2 . 204–8 . 1989 . 2571571 . 10.1016/0888-7543(89)90047-5 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Lu CM, Eichelberger JS, Beckman ML, etal . Isolation of the 5'-flanking region for human brain sodium channel subtype II alpha-subunit . J. Mol. Neurosci. . 11 . 3 . 179–82 . 1999 . 10344788 . 10.1385/JMN:11:3:179 . 33328638 .
• Baulac S, Gourfinkel-An I, Picard F, etal . A Second Locus for Familial Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2q21-q33 . Am. J. Hum. Genet. . 65 . 4 . 1078–85 . 2000 . 10486327 . 10.1086/302593 . 1288241 .
• Schade SD, Brown GB . Identifying the promoter region of the human brain sodium channel subtype II gene (SCN2A) . Brain Res. Mol. Brain Res. . 81 . 1–2 . 187–90 . 2001 . 11000491 . 10.1016/S0169-328X(00)00145-5 .
• Kasai N, Fukushima K, Ueki Y, etal . Genomic structures of SCN2A and SCN3A - candidate genes for deafness at the DFNA16 locus . Gene . 264 . 1 . 113–22 . 2001 . 11245985 . 10.1016/S0378-1119(00)00594-1 .
• Malacarne M, Gennaro E, Madia F, etal . Benign Familial Infantile Convulsions: Mapping of a Novel Locus on Chromosome 2q24 and Evidence for Genetic Heterogeneity . Am. J. Hum. Genet. . 68 . 6 . 1521–6 . 2001 . 11326335 . 10.1086/320596 . 1226140 .
• Sugawara T, Tsurubuchi Y, Agarwala KL, etal . A missense mutation of the Na+ channel αII subunit gene Nav1.2 in a patient with febrile and afebrile seizures causes channel dysfunction . Proc. Natl. Acad. Sci. U.S.A. . 98 . 11 . 6384–9 . 2001 . 11371648 . 10.1073/pnas.111065098 . 33477 . 2001PNAS...98.6384S . free .
• Heron SE, Crossland KM, Andermann E, etal . Sodium-channel defects in benign familial neonatal-infantile seizures . Lancet . 360 . 9336 . 851–2 . 2002 . 12243921 . 10.1016/S0140-6736(02)09968-3 . 6105850 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Weiss LA, Escayg A, Kearney JA, etal . Sodium channels SCN1A, SCN2A and SCN3A in familial autism . Mol. Psychiatry . 8 . 2 . 186–94 . 2003 . 12610651 . 10.1038/sj.mp.4001241 . 16606651 .
• Yu FH, Westenbroek RE, Silos-Santiago I, etal . Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2 . J. Neurosci. . 23 . 20 . 7577–85 . 2003 . 12930796 . 6740763 . 10.1523/JNEUROSCI.23-20-07577.2003.
• McEwen DP, Meadows LS, Chen C, etal . Sodium channel beta1 subunit-mediated modulation of Nav1.2 currents and cell surface density is dependent on interactions with contactin and ankyrin . J. Biol. Chem. . 279 . 16 . 16044–9 . 2004 . 14761957 . 10.1074/jbc.M400856200 . free .
• Kamiya K, Kaneda M, Sugawara T, etal . A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline . J. Neurosci. . 24 . 11 . 2690–8 . 2004 . 15028761 . 6729532 . 10.1523/JNEUROSCI.3089-03.2004 .
• Berkovic SF, Heron SE, Giordano L, etal . Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy . Ann. Neurol. . 55 . 4 . 550–7 . 2004 . 15048894 . 10.1002/ana.20029 . 11604421 .
• Pereira S, Vieira JP, Barroca F, etal . Severe epilepsy, retardation, and dysmorphic features with a 2q deletion including SCN1A and SCN2A . Neurology . 63 . 1 . 191–2 . 2004 . 15249644 . 10.1212/01.wnl.0000132844.20654.c1. 38453487 .

External links

Patient Organizations

The SCN2A Foundation

SCN2A Asia Pacific

SCN2A Germany e. V.

Notes and References

1. Web site: Entrez Gene: SCN2A sodium channel, voltage-gated, type II, alpha subunit.
2. Sanders SJ. Stephan J.. Murtha MT . Gupta AR . Murdoch JR . Raubeson MJ . Willsey AJ . Ercan-Sencicek AG . De novo mutations revealed by whole-exome sequencing are strongly associated with autism . Nature . 2012 . 10.1038/nature10945 . 22495306. etal . 485 . 7397. 237–241. 3667984 . 2012Natur.485..237S.
3. Sundaram SK, Chugani HT, Tiwari VN, Huq AH . SCN2A Mutation Is Associated With Infantile Spasms and Bitemporal Glucose Hypometabolism . Pediatr. Neurol. . 49 . 1 . 46–9 . July 2013 . 23827426 . 10.1016/j.pediatrneurol.2013.03.002 . 3868437.
4. Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. Genome-wide association study identifies 30 loci associated with bipolar disorder . Nature Genetics . 2019 . 10.1038/s41588-019-0397-8 . 31043756 . etal . 51 . 5 . 793–803. 10481/58017 . free . 6956732 .