protein
Calcium-activated potassium channel subunit alpha-1
Gene
KCNMA1
Organism
Homo sapiens(9606)
Length
1236 aa
Mass
137,560 Da
KCNMA1 encodes the calcium-activated potassium channel subunit alpha-1, a potassium channel activated by membrane depolarization or increased cytosolic calcium that mediates potassium export and repolarization of the cell membrane (UniProt: Q12791). The channel's kinetics are regulated by alternative splicing, phosphorylation, and association with modulatory beta subunits, and it plays critical roles in diverse physiological processes including smooth muscle contraction, cochlear hair cell tuning, neurotransmitter release, and innate immunity.
KCNMA1 is expressed across multiple tissues and contributes to excitability regulation in neuronal and non-neuronal systems. Mutations in KCNMA1 are associated with multiple neurological disorders including paroxysmal non-kinesigenic dyskinesia with or without generalized epilepsy, idiopathic generalized epilepsy, cerebellar atrophy with developmental delay and seizures, and Liang-Wang syndrome—a broadly defined autosomal dominant condition featuring developmental delay, intellectual disability, ataxia, and various malformations (UniProt: Q12791).
KCNMA1 has been classified as SFARI category 2 (strong candidate for syndromic autism) (SFARI Cat 2), indicating moderate evidence for association with autism spectrum disorder, particularly in syndromic presentations accompanied by seizures, developmental delay, and other neurological features.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+) (PubMed:14523450, PubMed:29330545, PubMed:31152168). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX). Possibly induces sleep when activated by melatonin and through melatonin receptor MTNR1A-dependent dissociation of G-beta and G-gamma subunits, leading to increased sensitivity to Ca(2+) and reduced synaptic transmission (PubMed:32958651)
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+)
Disease associations
Paroxysmal non-kinesigenic dyskinesia 3 with or without generalized epilepsyPNKD3
An autosomal dominant neurologic disorder characterized by absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia and involuntary dystonic or choreiform movements. Onset is usually in childhood. Patients may have seizures only, dyskinesia only, or both.
Epilepsy, idiopathic generalized 16EIG16
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG16 is characterized by onset of seizures soon after birth or in the first years of life.
Cerebellar atrophy, developmental delay, and seizuresCADEDS
An autosomal recessive disease characterized by epilepsy, developmental delay and severe cerebellar atrophy.
Liang-Wang syndromeLIWAS
An autosomal dominant syndrome characterized by a highly variable phenotype and severity. The broad spectrum of clinical features includes developmental delay, intellectual disability, ataxia, axial hypotonia, and poor or absent speech, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic craniofacial dysmorphism. About half of patients have cerebral and cerebellar atrophy, and thin corpus callosum.
Sources
Last updated 5/6/2026, 5:24:03 AM