CACNA1D
Homo sapiens
Gene Name: calcium channel, voltage-dependent, L type, alpha 1D
Aliases: CACH3, CACN4, CCHL1A2, CACNL1A2
Chromosome No: 3
Chromosome Band: 3p21.1
Genetic Category: Functional--Rare single gene variant-Syndromic-Genetic association-Rare single gene variant/Functional
Aliases: CACH3, CACN4, CCHL1A2, CACNL1A2
Chromosome No: 3
Chromosome Band: 3p21.1
Genetic Category: Functional--Rare single gene variant-Syndromic-Genetic association-Rare single gene variant/Functional
Summary Statistics:
ASD Reports: 33
Recent Reports: 4
Annotated variants: 70
Associated CNVs: 4
Evidence score: 4
ASD Reports: 33
Recent Reports: 4
Annotated variants: 70
Associated CNVs: 4
Evidence score: 4
Gene Score: 2
Associated Disorders: |
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Relevance to Autism
Rare de novo missnese variants in the CACNA1D gene have been identified in ASD probands from the Simons Simplex Collection (ORoak et al., 2012; Iossifov et al., 2012).
Molecular Function
The encoded protein has low voltage-gated calcium channel activity. Mutations in this gene are responsible for primary aldosteronism with seizures and neurologic abnormalities (PASNA; OMIM 615474).
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Positive Association
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.
SCZ
Support
The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing
ASD
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolesce...
ASD
Support
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.
Epilepsy
Support
New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy.
ASD, ID, epilepsy/seizures
Support
Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans.
ASD
Support
An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2)-dependent regulation.
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
DD, epilepsy/seizures
Support
The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.
ASD, epilepsy/seizures
Support
Contribution of CACNA1H Variants in Autism Spectrum Disorder Susceptibility
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Support
Pathogenicity of de novo CACNA1D Ca2+ channel variants predicted from sequence co-variation
ASD
Support
Gating defects of disease-causing de novo mutations in Cav1.3 Ca2+ channels.
Support
Identification of ultra-rare disruptive variants in voltage-gated calcium channel-encoding genes in Japanese samples of schizophrenia and autism spectrum disorder
ASD, SCZ
Support
Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism.
Support
NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital
ASD
Support
Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice.
Epilepsy/seizures
Support
Deletion of the voltage-gated calcium channel, Ca V 1.3, causes deficits in motor performance and associative learning
Support
Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities
Primary aldosteronism with seizures and neurologic
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Highly Cited
alpha 1D (Cav1.3) subunits can form l-type Ca2 channels activating at negative voltages.
Recent Recommendation
Functional roles of Cav1.3(alpha1D) calcium channels in atria: insights gained from gene-targeted null mutant mice.
Recent Recommendation
The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice
ASD
Recent Recommendation
CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels.
Recent Recommendation
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN032R012
missense_variant
c.1261G>A
p.Asp421Asn
Familial
Paternal
Simplex
GEN032R013
missense_variant
c.1792G>A
p.Gly598Ser
Familial
Paternal
Simplex
GEN032R014
missense_variant
c.2789G>A
p.Arg930His
Familial
Paternal
Simplex
GEN032R015
missense_variant
c.5816G>A
p.Arg1939Gln
Familial
Paternal
Simplex
GEN032R016
missense_variant
c.6053C>A
p.Thr2018Asn
Familial
Maternal
Simplex
GEN032R017
missense_variant
c.2612T>G
p.Leu871Trp
Familial
Paternal
Simplex
GEN032R018
missense_variant
c.2612T>G
p.Leu871Trp
Familial
Maternal
Simplex
GEN032R019
missense_variant
c.3433C>G
p.Arg1145Gly
Familial
Paternal
Simplex
GEN032R020
missense_variant
c.3607C>T
p.Arg1203Cys
Familial
Paternal
Simplex
GEN032R036
missense_variant
c.2015C>T
p.Ser672Leu
De novo
Unknown
GEN032R048
missense_variant
ENSG00000157388:ENST00000422281:exon21:c.A2771G:p.Y924C,ENSG00000157388:ENST00000288139:exon22:c.A28
De novo
GEN032R066
missense_variant
c.2015C>T
p.Ser672Leu
Familial
Paternal
Multiplex
GEN032R067
missense_variant
c.4967G>A
p.Arg1656His
Unknown
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN032C001
intergenic_variant
rs312477
G>A
40,675 SCZ cases and 64,643 controls (CLOZUK and independent PGC datasets)
Discovery