Human Gene Module / Chromosome 17 / CACNA1G

CACNA1Gcalcium channel, voltage-dependent, T type, alpha 1G subunit

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 21
Rare Variants / Common Variants
28 / 8
Aliases
CACNA1G, NBR13,  Cav3.1,  Ca(V)T.1,  MGC117234
Associated Syndromes
-
Chromosome Band
17q21.33
Associated Disorders
DD/NDD, EPS, ASD, ID
Relevance to Autism

Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (Strom et al., 2010). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2012).

Molecular Function

Voltage-activated calcium channels

Reports related to CACNA1G (21 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5' CpG island in human tumors Toyota M , et al. (1999) No -
2 Highly Cited Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels Kim D , et al. (2001) No -
3 Highly Cited T-type calcium channel regulation by specific G-protein betagamma subunits Wolfe JT , et al. (2003) No -
4 Recent Recommendation 17Beta-estradiol regulation of the mRNA expression of T-type calcium channel subunits: role of estrogen receptor alpha and estrogen receptor beta Bosch MA , et al. (2008) No -
5 Recent Recommendation Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence epilepsy Ernst WL , et al. (2009) No -
6 Primary High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene Strom SP , et al. (2009) Yes -
7 Recent Recommendation Three-dimensional structure of CaV3.1: comparison with the cardiac L-type voltage-gated calcium channel monomer architecture Walsh CP , et al. (2009) No -
8 Recent Recommendation Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive Park YG , et al. (2010) No -
9 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy Klassen T , et al. (2011) No -
10 Support De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
11 Support Support for calcium channel gene defects in autism spectrum disorders Lu AT , et al. (2012) Yes -
12 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
13 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
14 Support Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families Alazami AM , et al. (2015) No -
15 Recent Recommendation A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia Coutelier M , et al. (2015) No -
16 Recent Recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia Takata A , et al. (2016) No -
17 Recent Recommendation Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a Calhoun JD , et al. (2016) No -
18 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
19 Support De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene Chemin J , et al. (2018) No DD, ID, epilepsy/seizures, autistic behavior
20 Support Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing Bruel AL , et al. (2019) No -
21 Support - Li D et al. (2022) Yes -
Rare Variants   (28)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.557G>A p.Arg186Gln missense_variant Unknown - - 34968013 Li D et al. (2022)
T>A - splice_site_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
C>T - 2KB_upstream_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.2881G>A p.Ala961Thr missense_variant De novo NA - 29878067 Chemin J , et al. (2018)
c.4591A>G p.Met1531Val missense_variant De novo NA - 29878067 Chemin J , et al. (2018)
c.4591A>G p.Met1531Val missense_variant De novo NA - 31231135 Bruel AL , et al. (2019)
c.72C>G p.Asp24Glu missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.286G>A p.Val96Met missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.153G>A p.Leu51= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.546C>T p.Val182= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.915C>T p.Tyr305= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1345C>T p.Arg449Cys missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1556C>T p.Pro519Leu missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1464C>T p.Arg488= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1770T>C p.Tyr590= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1917G>A p.Gln639= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.4759C>T p.His1587Tyr missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.6109C>T p.Pro2037Ser missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.6542C>A p.Ser2181Tyr missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.561G>A p.Pro187= synonymous_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.4084C>T p.Leu1362= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.4956C>T p.Val1652= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.6348G>A p.Gln2116= synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.561G>A p.Pro187= synonymous_variant De novo NA Simplex 22542183 Iossifov I , et al. (2012)
c.4142G>A p.Arg1381Gln missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.667_669del p.Phe223del inframe_deletion Familial Both parents Multiplex 25558065 Alazami AM , et al. (2015)
c.3599A>G p.Asn1200Ser missense_variant De novo NA Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.5144G>A p.Arg1715His missense_variant Familial Maternal and paternal Multi-generational 26456284 Coutelier M , et al. (2015)
Common Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.243-2430T>C - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
c.243-620G>T T/G intron_variant - - - 23241247 Lu AT , et al. (2012)
c.243-3538C>T T/C intron_variant - - - 23241247 Lu AT , et al. (2012)
c.489-56T>G G/T intron_variant - - - 19455149 Strom SP , et al. (2009)
c.1141-29A>G;c.1141-80A>G A to G intron_variant - - - 19455149 Strom SP , et al. (2009)
c.2302-1483A>G;c.2251-1483A>G G/A intron_variant - - - 19455149 Strom SP , et al. (2009)
c.2301+3918A>G;c.2250+3918A>G A to G intron_variant - - - 19455149 Strom SP , et al. (2009)
c.2302-3203C>T;c.2251-3203C>T T to C intron_variant - - - 19455149 Strom SP , et al. (2009)
SFARI Gene score
2

Strong Candidate

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

Score Delta: Decreased from 4 to 3

2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2021
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

7/1/2021
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

4/1/2021
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

1/1/2021
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

10/1/2020
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

7/1/2020
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

4/1/2020
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

1/1/2020
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

4/1/2019
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

1/1/2019
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

10/1/2018
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

7/1/2018
4.3
icon
4

Decreased from 4.3 to 4

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

10/1/2017
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

4/1/2017
4
icon
4

Decreased from 4 to 4

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

Reports Added
[High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.2009] [De novo gene disruptions in children on the autistic spectrum.2012] [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] [Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5' CpG island in human tumors.1999] [Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2) channels.2001] [T-type calcium channel regulation by specific G-protein betagamma subunits.2003] [17Beta-estradiol regulation of the mRNA expression of T-type calcium channel subunits: role of estrogen receptor alpha and estrogen receptor beta.2008] [Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence e...2009] [Three-dimensional structure of CaV3.1: comparison with the cardiac L-type voltage-gated calcium channel monomer architecture.2009] [Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive.2010] [A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.2016] [Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a.2016] [Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...2017]
10/1/2016
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

4/1/2016
4
icon
4

Decreased from 4 to 4

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

Reports Added
[High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.2009] [De novo gene disruptions in children on the autistic spectrum.2012] [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] [Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5' CpG island in human tumors.1999] [Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2) channels.2001] [T-type calcium channel regulation by specific G-protein betagamma subunits.2003] [17Beta-estradiol regulation of the mRNA expression of T-type calcium channel subunits: role of estrogen receptor alpha and estrogen receptor beta.2008] [Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence e...2009] [Three-dimensional structure of CaV3.1: comparison with the cardiac L-type voltage-gated calcium channel monomer architecture.2009] [Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive.2010] [A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.2016] [Cacna1g is a genetic modifier of epilepsy caused by mutation of voltage-gated sodium channel Scn2a.2016]
1/1/2016
4
icon
4

Decreased from 4 to 4

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

Reports Added
[High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.2009] [De novo gene disruptions in children on the autistic spectrum.2012] [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] [Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.2015] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5' CpG island in human tumors.1999] [Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2) channels.2001] [T-type calcium channel regulation by specific G-protein betagamma subunits.2003] [17Beta-estradiol regulation of the mRNA expression of T-type calcium channel subunits: role of estrogen receptor alpha and estrogen receptor beta.2008] [Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence e...2009] [Three-dimensional structure of CaV3.1: comparison with the cardiac L-type voltage-gated calcium channel monomer architecture.2009] [Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive.2010] [A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014]
10/1/2015
4
icon
3

Decreased from 4 to 3

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

7/1/2015
5
icon
4

Decreased from 5 to 4

Description

Located in a linkage region with association not explaining linkage. Genetic association has been found between the CACNA1G gene and autism in the AGRE cohort (PMID 19455149) and a cohort using families from AGRE and AGP (PMID 23241247). Recently, a de novo synonymous variant in this gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). A homozygous in-frame deletion variant in the CACNA1G gene segregated with disease in a consanguineous multiplex family affected by severe intellectual disability (PMID 25558065).

10/1/2014
5
icon

Decreased from 5 to

Description

Located in a linkage region with association not explaining linkage.

7/1/2014
No data
icon
5

Increased from No data to 5

Description

Located in a linkage region with association not explaining linkage.

4/1/2014
No data
icon
5

Increased from No data to 5

Description

Located in a linkage region with association not explaining linkage.

Krishnan Probability Score

Score 0.61300357141815

Ranking 149/25841 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 0.99999651736233

Ranking 377/18225 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 0.94010158668807

Ranking 14446/18665 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).
Larsen Cumulative Evidence Score

Score 13

Ranking 148/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.10146750835663

Ranking 6107/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
Cacng6 calcium channel, voltage-dependent, gamma subunit 6 Rat Protein Binding 140727 Q8VHW7
KCND2 potassium voltage-gated channel, Shal-related subfamily, member 2 Human Protein Binding 3751 A4D0V9
LEF1 lymphoid enhancer-binding factor 1 Human DNA Binding 51176 Q659G9
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