geno logo
     HELP     Sign In

Quick Links

TOOLS
Search

Relevance to Autism

Rare mutations in the KCNMA1 gene have been identified with autism (Laumonnier et al., 2006; Neale et al., 2012).

Molecular Function

The encoded protein is the pore forming alpha subunit of large conductance, voltage and calcium-sensitive potassium channels. These channels are fundamental to the control of smooth muscle tone and neuronal excitability.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Association of a functional deficit of the BKCa channel, a synaptic regulator of neuronal excitability, with autism and mental retardation.
ASD
MR
Support
ID
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
ID, epilepsy/seizures
Support
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Support
A Gain-of-Function Mutation in KCNMA1 Causes Dystonia Spells Controlled With Stimulant Therapy
ASD, ADHD, ID
Dystonia
Support
Integrating de novo and inherited variants in 42
ASD
Support
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
ASD
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
Large-conductance calcium-activated potassium channel haploinsufficiency leads to sensory deficits in the visual system: a case report
ASD, ID
Support
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.
Epilepsy
Support
Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.
ASD
Macrocephaly
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurolo...
DD, ID
Support
A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
DD, ID, epilepsy/seizures
Support
Variantrecurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense v...
DD
Support
An emerging spectrum of variants and clinical features in KCNMA1-linked channelopathy
DD, ID, epilepsy/seizures
Highly Cited
A novel calcium-sensing domain in the BK channel.
Highly Cited
Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca(2) spark/STOC coupling and elevated blood pressure.
Recent Recommendation
Regulation of the gating of BKCa channel by lipid bilayer thickness.
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
BKCa-Cav channel complexes mediate rapid and localized Ca2+activated K signaling.
Recent Recommendation
Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder.
Recent Recommendation
Hydrophobic interface between two regulators of K conductance domains critical for calcium-dependent activation of large conductance Ca2+activate...
Recent Recommendation
Reciprocal regulation of the Ca2 and H sensitivity in the SLO1 BK channel conferred by the RCK1 domain.
Recent Recommendation
Mechanism of increased open probability by a mutation of the BK channel.
Recent Recommendation
The RCK1 high-affinity Ca2 sensor confers carbon monoxide sensitivity to Slo1 BK channels.
Recent Recommendation
Cytoplasmic BK(Ca) channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons.
Recent Recommendation
Regulation of mouse Slo gene expression: multiple promoters, transcription start sites, and genomic action of estrogen.
Recent Recommendation
De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN141R001 
 translocation 
  
  
 De novo 
  
 Possible multiplex 
 GEN141R002 
 missense_variant 
 c.413C>T 
 p.Ala138Val 
 Unknown 
  
 Simplex 
 GEN141R003 
 missense_variant 
 c.1114T>G 
 p.Phe372Val 
 De novo 
  
 Simplex 
 GEN141R004 
 synonymous_variant 
 c.762G>A 
 p.Thr254= 
 De novo 
  
 Simplex 
 GEN141R005 
 synonymous_variant 
 c.2229T>C 
 p.Ser743= 
 Unknown 
  
 Unknown 
 GEN141R006 
 synonymous_variant 
 c.2967G>A 
 p.Val989= 
 Unknown 
  
 Unknown 
 GEN141R007 
 splice_site_variant 
 NM_001014797.3:g.78374737A>G 
 p.? 
 Unknown 
  
 Unknown 
 GEN141R008 
 intron_variant 
 c.1223+2705C>T 
  
 De novo 
  
 Unknown 
 GEN141R009 
 missense_variant 
 c.2104+10495C>A 
  
 De novo 
  
  
 GEN141R010 
 missense_variant 
 c.1123G>A 
 p.Gly375Arg 
 De novo 
  
  
 GEN141R011 
 missense_variant 
 c.1123G>A 
 p.Gly375Arg 
 De novo 
  
  
 GEN141R012 
 missense_variant 
 c.1123G>A 
 p.Gly375Arg 
 De novo 
  
  
 GEN141R013 
 missense_variant 
 c.1123G>A 
 p.Gly375Arg 
 De novo 
  
  
 GEN141R014 
 missense_variant 
 c.1123G>A 
 p.Gly375Arg 
 De novo 
  
  
 GEN141R015 
 missense_variant 
 c.1052C>A 
 p.Ser351Tyr 
 De novo 
  
  
 GEN141R016 
 missense_variant 
 c.1066G>A 
 p.Gly356Arg 
 De novo 
  
  
 GEN141R017a 
 missense_variant 
 c.1238G>A 
 p.Cys413Tyr 
 Familial 
 Maternal 
  
 GEN141R017b 
 frameshift_variant 
  
 p.Asn449fs 
 Familial 
 Paternal 
  
 GEN141R018 
 missense_variant 
 c.1987A>G 
 p.Ile663Val 
 De novo 
  
  
 GEN141R019 
 missense_variant 
 c.2414C>T 
 p.Pro805Leu 
 De novo 
  
  
 GEN141R020 
 missense_variant 
 c.2950G>A 
 p.Val984Ile 
 De novo 
  
  
 GEN141R021 
 missense_variant 
 c.G3248G>A 
 p.Arg1083Lys 
 De novo 
  
 Simplex 
 GEN141R022 
 missense_variant 
 c.2935G>C 
 p.Ala979Pro 
 De novo 
  
 Simplex 
 GEN141R023 
 missense_variant 
 c.1606A>C 
 p.Asn536His 
 De novo 
  
 Simplex 
 GEN141R024 
 synonymous_variant 
 c.762G>A 
 p.Thr254= 
 De novo 
  
 Simplex 
 GEN141R025 
 intron_variant 
 c.2104+10495C>A 
  
 De novo 
  
 Simplex 
 GEN141R026 
 missense_variant 
 c.1606A>C 
 p.Asn536His 
 De novo 
  
  
 GEN141R027 
 splice_site_variant 
 c.2322+1765G>T 
  
 Unknown 
  
  
 GEN141R028 
 missense_variant 
 c.2984A>G 
 p.Asn995Ser 
 Unknown 
  
  
 GEN141R029 
 missense_variant 
 c.3482C>G 
 p.Pro1161Arg 
 Unknown 
  
  
 GEN141R030 
 missense_variant 
 c.2923G>C 
 p.Asp975His 
 De novo 
  
 Simplex 
 GEN141R031 
 synonymous_variant 
 c.2727G>A 
 p.Arg909%3D 
 De novo 
  
 Multiplex 
 GEN141R032 
 synonymous_variant 
 c.1347C>T 
 p.Asn449%3D 
 De novo 
  
 Multiplex 
 GEN141R033 
 missense_variant 
 c.1334A>G 
 p.Asn445Ser 
 De novo 
  
 Multiplex 
 GEN141R034 
 missense_variant 
 c.3059A>G 
 p.Asp1020Gly 
 De novo 
  
  
 GEN141R035 
 stop_gained 
 c.2481C>G 
 p.Ile827Met 
 De novo 
  
  
 GEN141R036 
 inframe_deletion 
 c.27_56del 
 p.Gly13_Ser22del 
 De novo 
  
  
 GEN141R037 
 frameshift_variant 
 c.3364dup 
 p.Met1122AsnfsTer4 
 De novo 
  
 Simplex 
  et al.  
 GEN141R038a 
 missense_variant 
 c.971C>T 
 p.Ser324Leu 
 Unknown 
  
  
  et al.  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
10
Duplication
 1
 
10
Deletion
 1
 
10
Deletion
 2
 
10
Deletion-Duplication
 16
 

Model Summary

Identification of previously unknown roles of potassium channels in mammalian cerebellar function and motor control. In addition, they provide a previously undescribed animal model of cerebellar ataxia.

References

Type
Title
Author, Year
Additional
Overactive bladder and incontinence in the absence of the BK large conductance Ca2+activated K channel.
Primary
Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2+activated K channel deficiency.
Additional
The role of BKCa channels in electrical signal encoding in the mammalian auditory periphery.

M_KCNMA1_3_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Floxed exon 1 of Kcnma1 with neomycin cassette inserted at 3' end of exon1 removed by mating with FVB/N-Tg(EIIa-cre)C5379Lmgd/J ubiquitously expressing Cre from the adenoviralEIIa promoter.
Allele Type: Targeted (knock-out)
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: FVB.129
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_KCNMA1_1_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A single loxp site inserted upstream of the exon encoding the pore-forming alpha subunit; a floxed neo-TK cassette downstream. Conditional cre-expression resulted in excision of the floxed region including the exon and neo-TK.
Allele Type: Targeted (knock-out)
Strain of Origin: C57BL/6
Genetic Background: 129/Sv * C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_KCNMA1_2_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A single loxp site inserted upstream of the exon encoding the pore-forming alpha subunit; a floxed neo-TK cassette downstream. Conditional cre-expression resulted in excision of the floxed region including the exon and neo-TK.
Allele Type: Targeted (knock-out)
Strain of Origin: 129 Svj
Genetic Background: 129
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_KCNMA1_3_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Grip strength1
Decreased
Description: Poor grip strength
Exp Paradigm: Hanging wire assay
 Wire hang test
 4-26 weeks
Gait1
Abnormal
Description: Uneven gait pattern
Exp Paradigm: Footprint analysis
 Footprint analysis
 >1 month
Ataxia1
Increased
Description: Moderate ataxia
Exp Paradigm: Footprint analysis
 Footprint analysis
 4-26 weeks
Motor coordination and balance1
Abnormal
Description: Mutant mice fall off an accelerating rotarod at significantly slower speeds compared to the wild-type
Exp Paradigm: Rota rod test
 Accelerating rotarod test
 1 month
Muscle fiber contraction1
Abnormal
Description: Urinary incontinence
Exp Paradigm: Abnormal
 Measurement of sponteneous phasic contractions of urinary bladder smooth muscle
 12.5 months
Size/growth1
Decreased
Description: Decreased body weight; 27% reduction
Exp Paradigm: General observations
 General observations
 P14
Reproductive system development1
Decreased
Description: Reduced efficiency of successful matings
Exp Paradigm: General observations
 General observations
 Adult
Mortality/lethality1
Increased
Description: Premature death due to unknown causes in 40% homozygotes
Exp Paradigm: General observations
 General observations
 0-10 weeks
Developmental trajectory1
Abnormal
Description: 6% of homozygotes display spontaneous and persistent unidirectional circling
Exp Paradigm: General observations
 General observations
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_KCNMA1_1_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Ataxia1
Increased
Description: Ataxia
Exp Paradigm: General observations
 General observations
 0-6 months
Motor coordination and balance1
Abnormal
Description: Impaired muscle coordination
Exp Paradigm: Balancing on a graded beam
 Balance beam test
 4-6 months
Motor coordination and balance1
Abnormal
Description: Impaired muscle coordination
Exp Paradigm: Accelerating rota rod test
 Accelerating rotarod test
 4-6 months
Tremor1
Increased
Description: Tremor
Exp Paradigm: General observations
 General observations
 0-6 months
Gait1
Abnormal
Description: Abnormal gait
Exp Paradigm: Footprint pattern analysis
 Footprint analysis
 3-6 months
Swimming ability1
Decreased
Description: Reduced swim speed and more frequent floating
Exp Paradigm: General observations
 General observations
 Unreported
Synaptic plasticity1
Decreased
Description: Significant reduction in spontaneous activity of cerebellar purkinje neurons
Exp Paradigm: Whole cell recordings
 Whole-cell patch clamp
 4-5 weeks
Synaptic plasticity1
Increased
Description: Increased short-term synaptic depression
Exp Paradigm: Whole-cell recordings from dcn neurons
 Whole-cell patch clamp
 P13-p17
Size/growth1
Decreased
Description: Reduced postnatal growth
Exp Paradigm: General observations
 General observations
 4, 8 weeks
Cardiovascular development and function1
Abnormal
Description: Moderate vascular dysfunction
Exp Paradigm: General observations
 General observations
 Unreported
Eye blink conditioning1
Abnormal
Description: Impaired learning of conditioned eye blink
Exp Paradigm: Conditioned eye-blink response
 Eyeblink conditioning
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_KCNMA1_2_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hearing1
Abnormal
Description: Abnormal cochlear nerve fiber response
Exp Paradigm: Auditory nerve recordings
 Auditory nerve recordings
 7-17 weeks
Hearing1
Abnormal
Description: Abnormal cochlear inner hair cell physiology
Exp Paradigm: Patch-clamp recordings from ihcs
 Whole-cell patch clamp
 P22-p30
Hearing1
Abnormal
Description: Abnormal cochlear ihc afferent innervation
Exp Paradigm: Auditory nerve recordings
 Auditory nerve recordings
 7-17 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Social behavior





Download KCNMA1's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
CACNA1C calcium channel, voltage-dependent, L type, alpha 1C subunit 24239 A0SLC4 IP/WB
IP; MS; IP/WB
Berkefeld H , et al. 2006
CACNA1H calcium channel, voltage-dependent, T type, alpha 1H subunit 8912 O95180 IP/WB; Immunohistochemistry; Electrophysiology
Rehak R , et al. 2013
KCNMB1 Calcium-activated potassium channel subunit beta-1 3779 Q16558 LRET
Castillo JP , et al. 2016
LRRC26 leucine rich repeat containing 26 389816 Q2I0M4 IP; LC-MS/MS; IP/WB
Yan J and Aldrich RW 2010
actin Actin, cytoplasmic 1, N-terminally processed 11461 P60710 MALDI-TOF; Immunohistochemistry; in vivo kinase assay; IP/WB
Ma D , et al. 2007
ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide 396529 P08251 Y2H; IP/WB; GST
Jha S and Dryer SE 2009
Cacna1h calcium channel, voltage-dependent, T type, alpha 1H subunit 58226 O88427 IP/WB
Chen CC , et al. 2003
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
FMR1 fragile X mental retardation 1 14265 P35922 IP/WB
Myrick LK , et al. 2015
Kcnma1 potassium large conductance calcium-activated channel, subfamily M, alpha member 1 16531 Q08460 IP/WB
Chiu YH , et al. 2010
KCNMB1 Calcium-activated potassium channel subunit beta-1 3779 Q16558 Electrophysiology
Sun X , et al. 2013
KCNMB2 potassium large conductance calcium-activated channel, subfamily M, beta member 2 10242 Q9Y691 Electrophysiology
Sun X , et al. 2013
Kirrel kin of IRRE like (Drosophila) 170643 Q80W68 IP/WB
Kim EY , et al. 2009
Magi1 membrane associated guanylate kinase, WW and PDZ domain containing 1 14924 Q6RHR9 Y2H; GST; IP/WB
Ridgway LD , et al. 2009
Neph1 Kin of IRRE-like protein 1 170643 Q80W68 GST; Electrophysiology; IP/WB
Kim EY , et al. 2009
PP2a-a Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform 19052 P63330 MALDI-TOF; Immunohistochemistry; in vivo kinase assay; IP/WB
Ma D , et al. 2007
pp2a-c Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform 19052 P63330 MALDI-TOF; Immunohistochemistry; in vivo kinase assay; IP/WB
Ma D , et al. 2007
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
SRC v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) 6714 P12931 WB
Yang Y , et al. 2009
Synpo synaptopodin 104027 Q8CC35 IP/WB; GST
Kim EY , et al. 2010
Trpc3 transient receptor potential cation channel, subfamily C, member 3 22065 Q9QZC1 IP/WB; GST
Kim EY , et al. 2008
Trpc6 transient receptor potential cation channel, subfamily C, member 6 22068 Q61143 IP/WB; GST
Kim EY , et al. 2008
tubulin Tubulin alpha-1A chain 22142 P68369 MALDI-TOF; Immunohistochemistry; in vivo kinase assay; IP/WB
Ma D , et al. 2007
Cacna1a calcium channel, voltage-dependent, P/Q type, alpha 1A subunit 25398 P54282 IP; MS
Berkefeld H , et al. 2006
Cacna1b calcium channel, voltage-dependent, N type, alpha 1B subunit 257648 Q02294 IP; MS
Berkefeld H , et al. 2006
Cacna1c calcium channel, voltage-dependent, L type, alpha 1C subunit 24239 A0SLC4 IP/WB
IP; MS; IP/WB
Berkefeld H , et al. 2006

HELP
Copyright © 2017 MindSpec, Inc.