KCNMA1

potassium calcium-activated channel subfamily M alpha 1, the group of Potassium calcium-activated channels

Basic information

Region (hg38): 10:76869601-77638369

Previous symbols: [ "SLO" ]

Links

ENSG00000156113 ∙ NCBI:3778 ∙ OMIM:600150 ∙ HGNC:6284 ∙ Uniprot:Q12791 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• generalized epilepsy-paroxysmal dyskinesia syndrome (Definitive), mode of inheritance: AD
• generalized epilepsy-paroxysmal dyskinesia syndrome (Moderate), mode of inheritance: AD
• Liang-Wang syndrome (Limited), mode of inheritance: AD
• generalized epilepsy-paroxysmal dyskinesia syndrome (Supportive), mode of inheritance: AD
• generalized epilepsy-paroxysmal dyskinesia syndrome (Strong), mode of inheritance: AD
• generalized epilepsy-paroxysmal dyskinesia syndrome (Strong), mode of inheritance: AD
• cerebellar atrophy, developmental delay, and seizures (Strong), mode of inheritance: AR
• generalized epilepsy-paroxysmal dyskinesia syndrome (Definitive), mode of inheritance: AD
• generalized epilepsy-paroxysmal dyskinesia syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, idiopathic generalized, susceptibility to, 16; Liang-Wang syndrome; Paroxysmal nonkinesigenic dyskinesia 3 with or without generalized epilepsy; Cerebellar atrophy, developmental delay, and seizures	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	15937479; 27567911; 29330545; 31152168

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNMA1 gene.

• Generalized epilepsy-paroxysmal dyskinesia syndrome (9 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNMA1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	275	4	285
missense	2	8	390	10	1	411
nonsense	1	1	2	1		5
start loss	1		1			2
frameshift	6	5	4			15
inframe indel			55	5		60
splice donor/acceptor (+/-2bp)		4	1			5
splice region			24	44	1	69
non coding			52	196	70	318
Total	10	18	511	487	75

Highest pathogenic variant AF is 0.00000657

Variants in KCNMA1

This is a list of pathogenic ClinVar variants found in the KCNMA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-76877888-T-C		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (-)
10-76877899-G-T		KCNMA1-related disorder	Likely benign (Jul 01, 2023)
10-76884892-C-CT		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jun 14, 2016)
10-76884940-G-T		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76884941-A-T		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76884988-C-T		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 12, 2018)
10-76885040-T-C		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 12, 2018)
10-76885083-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Likely benign (Jan 12, 2018)
10-76885128-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Likely benign (Jan 13, 2018)
10-76885149-C-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 12, 2018)
10-76885239-T-TTA		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jun 14, 2016)
10-76885309-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Benign (Jan 13, 2018)
10-76885329-A-C		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76885331-T-C		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 12, 2018)
10-76885379-C-T		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76885501-A-G		Generalized epilepsy-paroxysmal dyskinesia syndrome	Likely benign (Jan 13, 2018)
10-76885527-C-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76885633-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76885695-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Benign (Jan 12, 2018)
10-76885737-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76885759-C-T		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 13, 2018)
10-76885951-G-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Likely benign (Jan 13, 2018)
10-76885978-T-A		Generalized epilepsy-paroxysmal dyskinesia syndrome	Likely benign (Jan 12, 2018)
10-76885982-A-G		Generalized epilepsy-paroxysmal dyskinesia syndrome	Uncertain significance (Jan 12, 2018)
10-76886023-A-G		Generalized epilepsy-paroxysmal dyskinesia syndrome	Likely benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNMA1	protein_coding	protein_coding	ENST00000404857	28	768995

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00269	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.06	311	683	0.455	0.0000416	8042
Missense in Polyphen		63	270.96	0.2325		3202
Synonymous	-2.35	326	276	1.18	0.0000183	2335
Loss of Function	6.08	10	61.5	0.163	0.00000313	730

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000996	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). 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).
• Disease: DISEASE: Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy (PNKD3) [MIM:609446]: 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. {ECO:0000269|PubMed:15937479, ECO:0000269|PubMed:26195193}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vascular smooth muscle contraction - Homo sapiens (human);Renin secretion - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Splicing factor NOVA regulated synaptic proteins;Neuronal System;Hemostasis;Ca2+ activated K+ channels;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.140

Intolerance Scores

• loftool: 0.0246
• rvis_EVS: -1.68
• rvis_percentile_EVS: 2.65

Haploinsufficiency Scores

• pHI: 0.762
• hipred: Y
• hipred_score: 0.708
• ghis: 0.570

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.348

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnma1
• Phenotype: growth/size/body region phenotype; muscle phenotype; cellular phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: kcnma1b
• Affected structure: swimming behavior
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: response to hypoxia;potassium ion transport;response to osmotic stress;cellular potassium ion homeostasis;response to carbon monoxide;regulation of ion transmembrane transport;regulation of membrane potential;positive regulation of apoptotic process;negative regulation of cell volume;response to calcium ion;micturition;smooth muscle contraction involved in micturition;relaxation of vascular smooth muscle;potassium ion transmembrane transport
• Cellular component: plasma membrane;caveola;voltage-gated potassium channel complex;integral component of membrane;apical plasma membrane;postsynaptic membrane
• Molecular function: actin binding;voltage-gated potassium channel activity;protein binding;calcium-activated potassium channel activity;outward rectifier potassium channel activity;metal ion binding;large conductance calcium-activated potassium channel activity