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UniProtKB/Swiss-Prot Q99250: Variant p.Ala263Val

Sodium channel protein type 2 subunit alpha
Gene: SCN2A
Chromosomal location: 2q23-q24
Variant information

Variant position:  263
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Valine (V) at position 263 (A263V, p.Ala263Val).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from small size and hydrophobic (A) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Epileptic encephalopathy, early infantile, 11 (EIEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In EIEE11; also found in patients with neonatal epilepsy with late-onset episodic ataxia; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  263
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2005
The length of the canonical sequence.

Location on the sequence:   QSVKKLSDVMILTVFCLSVF  A LIGLQLFMGNLRNKCLQWPP
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPP

Mouse                         QSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPP

Rat                           QSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPP

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 2005 Sodium channel protein type 2 subunit alpha
Transmembrane 251 – 270 Helical; Name=S5 of repeat I
Repeat 111 – 456 I


Literature citations

SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain.
Liao Y.; Anttonen A.K.; Liukkonen E.; Gaily E.; Maljevic S.; Schubert S.; Bellan-Koch A.; Petrou S.; Ahonen V.E.; Lerche H.; Lehesjoki A.E.;
Neurology 75:1454-1458(2010)
Cited for: VARIANT EIEE11 VAL-263; CHARACTERIZATION OF VARIANT EIEE11 VAL-263;

Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings.
Touma M.; Joshi M.; Connolly M.C.; Grant P.E.; Hansen A.R.; Khwaja O.; Berry G.T.; Kinney H.C.; Poduri A.; Agrawal P.B.;
Epilepsia 54:E81-E85(2013)
Cited for: VARIANT EIEE11 VAL-263;

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.
Schwarz N.; Hahn A.; Bast T.; Mueller S.; Loeffler H.; Maljevic S.; Gaily E.; Prehl I.; Biskup S.; Joensuu T.; Lehesjoki A.E.; Neubauer B.A.; Lerche H.; Hedrich U.B.;
J. Neurol. 263:334-343(2016)
Cited for: VARIANTS VAL-263; ALA-1522 AND GLY-1882; CHARACTERIZATION OF VARIANTS ALA-1522 AND GLY-1882;

Letter to the editor: confirming neonatal seizure and late onset ataxia in SCN2A Ala263Val.
Johannesen K.M.; Miranda M.J.; Lerche H.; Moeller R.S.;
J. Neurol. 263:1459-1460(2016)
Cited for: VARIANT VAL-263;

Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes.
Parrini E.; Marini C.; Mei D.; Galuppi A.; Cellini E.; Pucatti D.; Chiti L.; Rutigliano D.; Bianchini C.; Virdo S.; De Vita D.; Bigoni S.; Barba C.; Mari F.; Montomoli M.; Pisano T.; Rosati A.; Guerrini R.;
Hum. Mutat. 38:216-225(2017)
Cited for: VARIANT GLY-191; VARIANTS EIEE11 ILE-251; VAL-263; VAL-896; VAL-1316; VAL-1323; TYR-1344; THR-1548 AND GLN-1882;

SCN2A p.Ala263Val Variant a Phenotype of Neonatal Seizures Followed by Paroxysmal Ataxia in Toddlers.
Gorman K.M.; King M.D.;
Pediatr. Neurol. 67:111-112(2017)
Cited for: VARIANT VAL-263;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.