KCNT1

Chr 9

potassium sodium-activated channel subfamily T member 1

Also known as: DEE14, EIEE14, ENFL5, KCa4.1, KNa1.1, SLACK, Slo2.2, bA100C15.2

NCBI Gene: 57582 ENSG00000107147 UniProt: Q5JUK3

This gene encodes a sodium-activated potassium channel subunit that regulates neuronal excitability and is involved in developmental signaling pathways. Mutations cause autosomal dominant epileptic disorders including developmental and epileptic encephalopathy 14 (malignant migrating partial seizures of infancy) and nocturnal frontal lobe epilepsy. Pathogenic variants predominantly cause disease through gain-of-function effects that alter channel conductance properties.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 14

UniProtEpilepsy, nocturnal frontal lobe, 5

Clinical highlights

Management implications

Gain-of-function KCNT1 may partially respond to quinidine (a KNa-channel blocker).Quinidine is a targeted (but inconsistent) option for GOF KCNT1 — monitor levels and QT.

KCNT1: treatment depends on gain/loss of function

Gene-disease validity (ClinGen)

childhood-onset epilepsy syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

GOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Treatment implicationsDepends on gain/loss of function

KCNT1-related epilepsy (EIMFS / sleep-related hypermotor epilepsy)

Quinidine is a targeted (but inconsistent) option for GOF KCNT1 — monitor levels and QT.

Gain-of-function KCNT1 may partially respond to quinidine (a KNa-channel blocker).

Gain-of-function

Gain-of-function → quinidine is a mechanism-targeted option; partial/variable response requiring plasma-level and QT monitoring.

Bearden 2014; Mullen et al. 2018, Neurology. Confirm with a neurologist and current guidelines. Functional class (GOF/LOF) is from published functional/segregation data, never inferred from the variant. As of 2026-07. Curated from the clinical genetics/neurology literature (cited per gene). Decision-support, not prescribing.