Human Gene SCN1A (ENST00000375405.7) from GENCODE V44
Description: Homo sapiens sodium voltage-gated channel alpha subunit 1 (SCN1A), transcript variant 8, mRNA. (from RefSeq NM_001353951) RefSeq Summary (NM_001165963): Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]. 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: ENST00000375405.7 Gencode Gene: ENSG00000144285.23 Transcript (Including UTRs) Position: hg38 chr2:165,989,163-166,073,639 Size: 84,477 Total Exon Count: 26 Strand: - Coding Region Position: hg38 chr2:165,991,245-166,073,621 Size: 82,377 Coding Exon Count: 26
ID:SCN1A_HUMAN DESCRIPTION: RecName: Full=Sodium channel protein type 1 subunit alpha; AltName: Full=Sodium channel protein brain I subunit alpha; AltName: Full=Sodium channel protein type I subunit alpha; AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.1; 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. SUBUNIT: The sodium channel consists of a large polypeptide and 2- 3 smaller ones. This sequence represents a large polypeptide. Interacts with FGF13; may regulate SCN1A activity. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. 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. DISEASE: Defects in SCN1A are the cause of generalized epilepsy with febrile seizures plus type 2 (GEFS+2) [MIM:604403]. Generalized epilepsy with febrile seizures-plus refers to 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. GEFS+ is a disease combining 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 SCN1A are a cause of severe myoclonic epilepsy in infancy (SMEI) [MIM:607208]; also called Dravet syndrome. SMEI is a rare disorder characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. SMEI is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus. DISEASE: Defects in SCN1A are a cause of intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC) [MIM:607208]. ICEGTC is a disorder characterized by generalized tonic-clonic seizures beginning usually in infancy and induced by fever. Seizures are associated with subsequent mental decline, as well as ataxia or hypotonia. ICEGTC is similar to SMEI, except for the absence of myoclonic seizures. DISEASE: Defects in SCN1A are the cause of familial hemiplegic migraine type 3 (FHM3) [MIM:609634]. FHM3 is an autosomal dominant severe subtype of migraine with aura characterized by some degree of hemiparesis during the attacks. The episodes are associated with variable features of nausea, vomiting, photophobia, and phonophobia. Age at onset ranges from 6 to 15 years. FHM is occasionally associated with other neurologic symptoms such as cerebellar ataxia or epileptic seizures. A unique eye phenotype of elicited repetitive daily blindness has also been reported to be cosegregating with FHM in a single Swiss family. DISEASE: Defects in SCN1A are the cause of familial febrile convulsions type 3A (FEB3A) [MIM:604403]; also known as familial febrile seizures 3. Febrile convulsions are 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. Nav1.1/SCN1A subfamily. SIMILARITY: Contains 1 IQ domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN1A";
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 P35498
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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
Biological Process: GO:0001508 action potential GO:0006811 ion transport GO:0006814 sodium ion transport GO:0007628 adult walking behavior GO:0019227 neuronal action potential propagation GO:0019228 neuronal action potential GO:0034220 ion transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0035725 sodium ion transmembrane transport GO:0042391 regulation of membrane potential GO:0050884 neuromuscular process controlling posture GO:0050966 detection of mechanical stimulus involved in sensory perception of pain GO:0055085 transmembrane transport GO:0086002 cardiac muscle cell action potential involved in contraction GO:0086010 membrane depolarization during action potential
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