Sodium channel protein type 1 subunit alpha

UniProt P35498 Organism Homo sapiens Gene NAC1, SCN1, SCN1A

Also known as: NAC1, SCN1, SCN1A

Function

Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues. By regulating the excitability of neurons, ensures that they respond appropriately to synaptic inputs, maintaining the balance between excitation and inhibition in brain neural circuits (By similarity). Nav1.1 plays a role in controlling the excitability and action potential propagation from somatosensory neurons, thereby contributing to the sensory perception of mechanically-induced pain (By similarity).

Classification

Family (Pfam): PF00520 Ion_trans, PF24609 IQ_SCN5A_C, PF06512 Na_trans_assoc, PF11933 Na_trans_cytopl
InterPro: Ion_trans_dom, IQ_SCN5A_C, Na_channel_a1su, Na_channel_asu, Na_chnl_inactivation_gate, Na_trans_assoc_dom, Na_trans_cytopl, VGCC_Ca_Na, Volt_channel_dom_sf
Functional cluster: DEAD-Box RNA Helicases & Biogenesis Factors

Experimental structures · PDB · 1

7DTD EM 3.30A

A predicted model is available from AlphaFold.

Gene Ontology · 15

Disease associations

generalized epilepsy with febrile seizures plus, type 2 MONDO:0011461
developmental and epileptic encephalopathy, 6A MONDO:0100079
migraine, familial hemiplegic, 3 MONDO:0012320
developmental and epileptic encephalopathy 6B MONDO:0030268

Drugs targeting this protein · 55

Neighborhood · nearest proteins

Nearest neighbours of Sodium channel protein type 1 subunit alpha: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Sodium channel protein type 2 subunit alpha 16 shared papers
Sodium channel regulatory subunit beta-1 3 shared papers
Sodium channel regulatory subunit beta-4 1 shared papers
Fibroblast growth factor 13 1 shared papers
Gamma-aminobutyric acid receptor subunit beta-3 3 shared papers
Phospholipid phosphatase-related protein type 4 1 shared papers
Phospholipid phosphatase-related protein type 4 1 shared papers
Sodium channel protein type 5 subunit alpha 2 shared papers
Sodium channel protein type 3 subunit alpha 2 shared papers
Syntaxin-binding protein 1 5 shared papers
Beta/delta-theraphotoxin-Pre1a 1 shared papers
Sodium channel protein type 8 subunit alpha 7 shared papers

Literature · 96 cited papers

Functional characteristics of the Nav1.1 p.Arg1596Cys mutation associated with varying severity of epilepsy phenotypes. Int. J. Mol. Sci. · 2024
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nat. Commun. · 2023
Mutations in plasticity-related-gene-1 (PRG-1) protein contribute to hippocampal seizure susceptibility and modify epileptic phenotype. Cereb. Cortex · 2023
Comparative structural analysis of human Nav1.1 and Nav1.5 reveals mutational hotspots for sodium channelopathies. Proc. Natl. Acad. Sci. U.S.A. · 2021
De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay. PLoS Genet. · 2018
Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype. Neurology · 2017
A mutation in GABRB3 associated with Dravet syndrome. Am. J. Med. Genet. A · 2017
The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity. Sci. Rep. · 2017
Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 2017
Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis. J. Med. Genet. · 2016
Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms. Neuron · 2015
Missense mutations in sodium channel SCN1A and SCN2A predispose children to encephalopathy with severe febrile seizures. Epilepsy Res. · 2015
… and 84 more in the literature graph

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