Human Gene Module / Chromosome 12 / CACNA1C

CACNA1Ccalcium channel, voltage-dependent, L type, alpha 1C subunit

Score
S
Syndromic Syndromic
Autism Reports / Total Reports
10 / 39
Rare Variants / Common Variants
30 / 9
Aliases
CACNA1C, TS,  CACH2,  CACN2,  CaV1.2,  CCHL1A1,  CACNL1A1
Associated Syndromes
Timothy syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association
Chromosome Band
12p13.33
Associated Disorders
BPD, ASD, ID, EPS
Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, mutation of the CACNA1C gene has been found to be associated with Timothy syndrome, patients which all also fall under the category of ASD. In addition, several studies have shown a genetic association between the CACNA1C gene and schizophrenia as well as bipolar disorder.

Molecular Function

This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization.

Reports related to CACNA1C (39 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A beta2 adrenergic receptor signaling complex assembled with the Ca2 channel Cav1.2. Davare MA , et al. (2001) No -
2 Primary Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Splawski I , et al. (2004) No ASD
3 Recent Recommendation Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Splawski I , et al. (2005) No -
4 Recent Recommendation Neuronal localization of Ca(v)1.2 L-type calcium channels in the rat basolateral amygdala. Pinard CR , et al. (2005) No -
5 Recent Recommendation AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2 channel activity and nuclear signaling. Oliveria SF , et al. (2007) No -
6 Recent Recommendation The tumor suppressor eIF3e mediates calcium-dependent internalization of the L-type calcium channel CaV1.2. Green EM , et al. (2007) No -
7 Recent Recommendation Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice. White JA , et al. (2008) No -
8 Recent Recommendation The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. Barrett CF and Tsien RW (2008) No -
9 Recent Recommendation beta-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a beta-arrestin 1-mediated pathway. Lipsky R , et al. (2008) No -
10 Recent Recommendation Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Ferreira MA , et al. (2008) No -
11 Recent Recommendation Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for o... Moskvina V , et al. (2008) No -
12 Recent Recommendation The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. Yarotskyy V , et al. (2008) No -
13 Recent Recommendation Genetic variation in CACNA1C affects brain circuitries related to mental illness. Bigos KL , et al. (2010) No -
14 Recent Recommendation The Cav subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. Altier C , et al. (2010) No -
15 Support Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Schaaf CP , et al. (2011) Yes -
16 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Klassen T , et al. (2011) No -
17 Recent Recommendation -Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a -arrestin 1-mediated pathway. no authors (2011) No -
18 Positive association Genome-wide association study identifies five new schizophrenia loci. Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) No -
19 Support Support for calcium channel gene defects in autism spectrum disorders. Lu AT , et al. (2012) Yes -
20 Recent Recommendation Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Krey JF , et al. (2013) No -
21 Positive association Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) Yes -
22 Recent Recommendation Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long... Boczek NJ , et al. (2013) No -
23 Recent Recommendation Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese. Zhang X , et al. (2013) No -
24 Support Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Jiang YH , et al. (2013) Yes -
25 Recent Recommendation A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CAC... Gershon ES , et al. (2013) No BPD
26 Support Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut... Koshimizu E , et al. (2013) Yes ID, epilepsy
27 Support Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ... Brett M , et al. (2014) Yes MCA
28 Recent recommendation CACNA1C risk variant affects reward responsiveness in healthy individuals. Lancaster TM , et al. (2014) No -
29 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
30 Recent recommendation Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons. Yoshimizu T , et al. (2014) No -
31 Recent recommendation Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. Wemhner K , et al. (2015) No -
32 Positive association Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism. Li J , et al. (2015) Yes -
33 Support Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms. D'Gama AM , et al. (2015) Yes -
34 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder. Alvarez-Mora MI , et al. (2016) Yes -
35 Recent recommendation The Neuropsychiatric Disease-Associated Gene cacna1c Mediates Survival of Young Hippocampal Neurons. Lee AS , et al. (2016) No -
36 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Redin C , et al. (2016) No -
37 Positive association Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Pardias AF , et al. (2018) No -
38 Recent recommendation A Critical Neurodevelopmental Role for L-Type Voltage-Gated Calcium Channels in Neurite Extension and Radial Migration. Kamijo S , et al. (2018) No -
39 Highly Cited N-methyl-D-aspartate receptor-induced proteolytic conversion of postsynaptic class C L-type calcium channels in hippocampal neurons. Hell JW , et al. (1996) No -
Rare Variants   (30)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1216G>A p.Gly406Arg missense_variant De novo - Simplex, multiplex 15454078 Splawski I , et al. (2004)
c.1204G>A p.Gly402Ser missense_variant De novo - Simplex 15863612 Splawski I , et al. (2005)
c.718C>T p.Arg240Cys missense_variant Familial Maternal Simplex 21624971 Schaaf CP , et al. (2011)
c.911T>C p.Ile304Thr missense_variant Familial - Simplex 21624971 Schaaf CP , et al. (2011)
c.1486G>A p.Gly490Arg missense_variant Familial - Simplex 21624971 Schaaf CP , et al. (2011)
c.2437G>A p.Gly813Arg missense_variant Familial Paternal Simplex 21624971 Schaaf CP , et al. (2011)
c.2449C>T p.Pro817Ser missense_variant Familial Maternal (1 case) Simplex 21624971 Schaaf CP , et al. (2011)
c.2807T>G p.Phe936Cys missense_variant Familial - Simplex 21624971 Schaaf CP , et al. (2011)
c.4966G>A p.Ala1656Thr missense_variant Familial - Simplex 21624971 Schaaf CP , et al. (2011)
c.5242G>A p.Gly1748Ser missense_variant Familial Maternal (1 case) Simplex 21624971 Schaaf CP , et al. (2011)
c.5293G>A p.Ala1765Thr missense_variant Familial Paternal Simplex 21624971 Schaaf CP , et al. (2011)
c.5527G>A p.Gly1843Arg missense_variant Familial - Simplex 21624971 Schaaf CP , et al. (2011)
c.5738T>C p.Leu1913Pro missense_variant Familial Paternal Simplex 21624971 Schaaf CP , et al. (2011)
c.5809C>T p.Arg1937Cys missense_variant Familial Maternal (1 case) Simplex 21624971 Schaaf CP , et al. (2011)
c.6184G>A p.Val2062Ile missense_variant Familial Paternal Simplex 21624971 Schaaf CP , et al. (2011)
c.906G>A p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.2637G>A p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.4761G>A p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.5292C>T p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.5097C>T p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.5478G>A p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
C>A - intron_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.4565G>A p.Arg1122His missense_variant Familial Paternal Simplex 23849776 Jiang YH , et al. (2013)
c.4706C>T p.Pro1569Leu missense_variant Unknown - Unknown 24066114 Koshimizu E , et al. (2013)
c.6272A>G p.Asn2091Ser missense_variant Unknown Not maternal - 24690944 Brett M , et al. (2014)
c.3544G>C p.Val1182Leu missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.3416G>A p.Arg1139His missense_variant Unknown - Multiplex or multi-generational 26637798 D'Gama AM , et al. (2015)
c.2T>C - initiator_codon_variant Unknown - Unknown 26637798 D'Gama AM , et al. (2015)
- p.Val2019Ile missense_variant Familial Maternal Multi-generational 26845707 Alvarez-Mora MI , et al. (2016)
- - translocation De novo - - 27841880 Redin C , et al. (2016)
Common Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.477+115699G>A;c.567+115699G>A;c.486+115699G>A - intron_variant - - - 18711365 Ferreira MA , et al. (2008)
N/A - allele - - - 19065143 Moskvina V , et al. (2008)
c.477+115699G>A;c.567+115699G>A;c.486+115699G>A - intron_variant - - - 20819988 Bigos KL , et al. (2010)
c.477+119988G>C;c.567+119988G>C;c.486+119988G>C C/G intron_variant - - - 21926974 Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011)
c.478-70203A>G;c.568-70203A>G;c.487-70203A>G G/A intron_variant - - - 23241247 Lu AT , et al. (2012)
c.478-155896A>G;c.568-155896A>G;c.487-155896A>G - intron_variant - - - 23453885 Cross-Disorder Group of the Psychiatric Genomics Consortium (2013)
c.477+115699G>A;c.567+115699G>A;c.486+115699G>A - intron_variant - - - 26204268 Li J , et al. (2015)
c.477+119988G>C;c.567+119988G>C;c.486+119988G>C - intron_variant - - - 26204268 Li J , et al. (2015)
c.477+115364A>G;c.567+115364A>G;c.486+115364A>G - intron_variant - - - 29483656 Pardias AF , et al. (2018)
SFARI Gene score
S

Syndromic

S

Score Delta: Score remained at S

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2016
S
icon
S

Score remained at S

Description

Timothy Syndrome gene (Splawski et al., 2004; PMID: 15454078); no additional evidence it is involved in idiopathic autism.

4/1/2016
S
icon
S

Score remained at S

Description

Timothy Syndrome gene (Splawski et al., 2004; PMID: 15454078); no additional evidence it is involved in idiopathic autism.

Reports Added
[Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [The tumor suppressor eIF3e mediates calcium-dependent internalization of the L-type calcium channel CaV1.2.2007] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [N-methyl-D-aspartate receptor-induced proteolytic conversion of postsynaptic class C L-type calcium channels in hippocampal neurons.1996] [Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.2013] [The Cav subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels.2010] [Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.2008] [Genetic variation in CACNA1C affects brain circuitries related to mental illness.2010] [Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for o...2008] [Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.2014] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [The Neuropsychiatric Disease-Associated Gene cacna1c Mediates Survival of Young Hippocampal Neurons.2016] [Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice.2008] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation.2008] [Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.2015] [The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.2008] [Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.2005] [Genome-wide association study identifies five new schizophrenia loci.2011] [A beta2 adrenergic receptor signaling complex assembled with the Ca2 channel Cav1.2.2001] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [CACNA1C risk variant affects reward responsiveness in healthy individuals.2014] [Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons.2013] [-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a -arrestin 1-mediated pathway.2011] [Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long...2013] [Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese.2013] [Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.2004] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CAC...2013] [Neuronal localization of Ca(v)1.2 L-type calcium channels in the rat basolateral amygdala.2005] [beta-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a beta-arrestin 1-mediated pathway.2008] [Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome.2015] [Support for calcium channel gene defects in autism spectrum disorders.2012] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2 channel activity and nuclear signaling.2007]
1/1/2016
S
icon
S

Score remained at S

Description

Timothy Syndrome gene (Splawski et al., 2004; PMID: 15454078); no additional evidence it is involved in idiopathic autism.

Reports Added
[Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [The tumor suppressor eIF3e mediates calcium-dependent internalization of the L-type calcium channel CaV1.2.2007] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [N-methyl-D-aspartate receptor-induced proteolytic conversion of postsynaptic class C L-type calcium channels in hippocampal neurons.1996] [Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.2013] [The Cav subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels.2010] [Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.2008] [Genetic variation in CACNA1C affects brain circuitries related to mental illness.2010] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for o...2008] [Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice.2008] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation.2008] [Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.2015] [Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.2014] [The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.2008] [Genome-wide association study identifies five new schizophrenia loci.2011] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [CACNA1C risk variant affects reward responsiveness in healthy individuals.2014] [-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a -arrestin 1-mediated pathway.2011] [Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long...2013] [Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese.2013] [Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons.2013] [Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.2004] [Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.2005] [A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CAC...2013] [A beta2 adrenergic receptor signaling complex assembled with the Ca2 channel Cav1.2.2001] [Neuronal localization of Ca(v)1.2 L-type calcium channels in the rat basolateral amygdala.2005] [beta-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a beta-arrestin 1-mediated pathway.2008] [Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome.2015] [Support for calcium channel gene defects in autism spectrum disorders.2012] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2 channel activity and nuclear signaling.2007]
7/1/2015
S
icon
S

Score remained at S

Description

Timothy Syndrome gene (Splawski et al., 2004; PMID: 15454078); no additional evidence it is involved in idiopathic autism.

Reports Added
[The tumor suppressor eIF3e mediates calcium-dependent internalization of the L-type calcium channel CaV1.2.2007] [N-methyl-D-aspartate receptor-induced proteolytic conversion of postsynaptic class C L-type calcium channels in hippocampal neurons.1996] [Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.2013] [The Cav subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels.2010] [Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.2008] [Genetic variation in CACNA1C affects brain circuitries related to mental illness.2010] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice.2008] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for o...2008] [The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation.2008] [Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.2014] [Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.2015] [The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.2008] [Genome-wide association study identifies five new schizophrenia loci.2011] [A beta2 adrenergic receptor signaling complex assembled with the Ca2 channel Cav1.2.2001] [Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.2005] [-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a -arrestin 1-mediated pathway.2011] [Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long...2013] [Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese.2013] [Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.2004] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CAC...2013] [Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons.2013] [Neuronal localization of Ca(v)1.2 L-type calcium channels in the rat basolateral amygdala.2005] [beta-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a beta-arrestin 1-mediated pathway.2008] [Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome.2015] [Support for calcium channel gene defects in autism spectrum disorders.2012] [Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.2011] [CACNA1C risk variant affects reward responsiveness in healthy individuals.2014] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2 channel activity and nuclear signaling.2007]
1/1/2015
S
icon
S

Score remained at S

Description

Timothy Syndrome gene (Splawski et al., 2004; PMID: 15454078); no additional evidence it is involved in idiopathic autism.

4/1/2014
No data
icon
S

Score remained at S

Description

Timothy Syndrome gene (Splawski et al., 2004; PMID: 15454078); no additional evidence it is involved in idiopathic autism.

Krishnan Probability Score

Score 0.58259012642518

Ranking 558/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.99999843310185

Ranking 330/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.9475567137724

Ranking 17324/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score

Score 0.37223369655839

Ranking 1765/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
CNVs associated with CACNA1C(1 CNVs)
12p13.33 30 Deletion-Duplication 46  /  198
Animal Models associated with CACNA1C(1 Models)
CACNA1C_7_KI_HT_G406R 1 Genetic Mus musculus
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
AHNAK AHNAK nucleoprotein Human Protein Binding 79026 Q09666
AKAP7 A kinase (PRKA) anchor protein 7 Human Protein Binding 9465 O43687
ANKRD35 ankyrin repeat domain 35 Human Protein Binding 148741 Q8N283
BIN1 bridging integrator 1 Human Protein Binding 274 O00499
BSG basigin (Ok blood group) Human Protein Binding 682 P35613
C18orf32 chromosome 18 open reading frame 32 Human Protein Binding 497661 Q8TCD1
CABP1 calcium binding protein 1 Human Protein Binding 9478 Q9NZU7
CACNB1 calcium channel, voltage-dependent, beta 1 subunit Human Protein Binding 775 Q13936
CACNB2 calcium channel, voltage-dependent, beta 2 subunit Human Protein Binding 783 Q08289
CACNB3 calcium channel, voltage-dependent, beta 3 subunit Human Protein Binding 784 P54284
CACNB4 calcium channel, voltage-dependent, beta 4 subunit Human Protein Binding 785 O00305
Camk2a calcium/calmodulin-dependent protein kinase II alpha Rat Protein Binding 25400 P11275
DNAJA3 DnaJ (Hsp40) homolog, subfamily A, member 3 Human Protein Binding 9093 Q96EY1
EFEMP1 EGF containing fibulin-like extracellular matrix protein 1 Human Protein Binding 2202 Q12805
EIF3E eukaryotic translation initiation factor 3, subunit E Human Protein Binding 3646 P60228
FHL2 four and a half LIM domains 2 Human Protein Binding 2274 Q14192
GABBR2 gamma-aminobutyric acid (GABA) B receptor, 2 Human Protein Binding 9568 O75899
IFT88 intraflagellar transport 88 homolog (Chlamydomonas) Human Protein Binding 8100 Q13099
KCNIP2 Kv channel interacting protein 2 Human Protein Binding 30819 Q9NS61
KCNMA1 potassium large conductance calcium-activated channel, subfamily M, alpha member 1 Human Protein Binding 3778 Q12791
NUP133 nucleoporin 133kDa Human Protein Binding 55746 Q8WUM0
PIKFYVE phosphoinositide kinase, FYVE finger containing Human Protein Binding 200576 Q9Y2I7
Ppm1a protein phosphatase 1A, magnesium dependent, alpha isoform Rat Protein Binding 24666 P20650
PPP2R4 protein phosphatase 2A activator, regulatory subunit 4 Human Protein Binding 5524 Q15257
PPP3CB protein phosphatase 3, catalytic subunit, beta isozyme Human Protein Binding 5532 P16298
PRKACA protein kinase, cAMP-dependent, catalytic, alpha Human Protein Modification 5566 P17612
RIC3 resistance to inhibitors of cholinesterase 3 homolog (C. elegans) Human Protein Binding 79608 Q7Z5B4
RIMS2 regulating synaptic membrane exocytosis 2 Human Protein Binding 9699 Q9UQ26
RYR1 ryanodine receptor 1 (skeletal) Rabbit Protein Binding 100009540 P11716
S100A10 S100 calcium binding protein A10 Human Protein Binding 6281 P60903
SRI sorcin Human Protein Binding 6717 P30626
SRRT serrate RNA effector molecule homolog (Arabidopsis) Human Protein Binding 51593 Q9BXP5
STIM1 stromal interaction molecule 1 Human Protein Binding 6786 Q13586
TNIP2 TNFAIP3 interacting protein 2 Human Protein Binding 79155 Q8NFZ5
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