SCN1A

SCN1A encodes the pore-forming α-subunit of Nav1.1, the most clinically important voltage-gated sodium channel in epilepsy genetics. As a 24-transmembrane domain protein, SCN1A directly mediates the depolarizing phase of action potentials through voltage-dependent conformational switching that allows selective Na+ influx along electrochemical gradients. Nav1.1 is particularly critical in GABAergic interneurons where it regulates inhibitory neuron excitability - loss-of-function mutations impair interneuron function leading to network hyperexcitability and seizures. SCN1A mutations cause >80% of Dravet syndrome cases and represent the most frequent target of epilepsy-related mutations, causing a phenotypic spectrum from febrile seizures (GEFS+) to severe developmental epileptic encephalopathy. The protein localizes to specialized membrane domains including axon initial segments, nodes of Ranvier, and neuronal cell bodies where it enables action potential initiation, propagation, and presynaptic membrane potential regulation. Understanding SCN1A pathophysiology has revealed that sodium channel blockers are contraindicated in SCN1A-related epilepsies as they worsen seizures by further impairing already compromised interneuron excitability.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.