Human Gene Module / Chromosome X / CACNA1F

CACNA1Fcalcium channel, voltage-dependent, alpha 1F

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 9
Rare Variants / Common Variants
7 / 2
Aliases
CACNA1F, JM8,  JMC8,  CSNB2,  CSNBX2
Associated Syndromes
-
Chromosome Band
Xp11.23
Associated Disorders
-
Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. Genetic association has also been found between the CACNA1F gene and schizophrenia in a Caucasian-European cohort from the UK population (Wei and Hemmings, 2006).

Molecular Function

The encoded protein has low voltage-gated calcium channel activity.

SFARI Genomic Platforms
Reports related to CACNA1F (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution McRory JE , et al. (2004) No -
2 Recent Recommendation Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina Mansergh F , et al. (2005) No -
3 Recent Recommendation A further study of a possible locus for schizophrenia on the X chromosome Wei J and Hemmings GP (2006) No -
4 Recent Recommendation Calmodulin is a functional regulator of Cav1.4 L-type Ca2+ channels Griessmeier K , et al. (2009) No -
5 Recent Recommendation Congenital stationary night blindness in mice - a tale of two Cacna1f mutants Lodha N , et al. (2010) No -
6 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy Klassen T , et al. (2011) No -
7 Support A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders Suzuki T et al. (2020) Yes -
8 Support - Viggiano M et al. (2022) Yes -
9 Primary An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness Strom TM , et al. (1998) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G>A - intron_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
C>T p.(=) synonymous_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.40C>A p.Pro14Thr missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.5081G>A p.Gly1694Glu missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.4048G>A p.Gly1350Ser missense_variant Familial Maternal - 35350424 Viggiano M et al. (2022)
c.4255G>A p.Ala1419Thr missense_variant Familial Maternal - 35350424 Viggiano M et al. (2022)
c.2441_2442insAGAAGA p.Glu824_Glu825dup inframe_insertion Familial Maternal Simplex 32530565 Suzuki T et al. (2020)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.382-36C>T;c.382-36T>C;c.187-36C>T;c.187-36T>C N/A intron_variant - - - 16650384 Wei J and Hemmings GP (2006)
c.3813+68A>G;c.3813+68G>A;c.3651+68A>G;c.3651+68G>A;c.3846+68A>G;c.3846+68G>A N/A intron_variant - - - 16650384 Wei J and Hemmings GP (2006)
SFARI Gene score
2

Strong Candidate

A significant but unreplicated association with ASD has been reported (Myers et al., 2011).

Score Delta: Score remained at 2

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A significant but unreplicated association with ASD has been reported (Myers et al., 2011).

7/1/2020
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association with ASD has been reported (Myers et al., 2011).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A significant but unreplicated association with ASD has been reported (Myers et al., 2011).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

A significant but unreplicated association with ASD has been reported (Myers et al., 2011).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A significant but unreplicated association with ASD has been reported (Myers et al., 2011).

Krishnan Probability Score

Score 0.48700961248523

Ranking 7077/25841 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 0.87370360449603

Ranking 3437/18225 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 0.9480154290156

Ranking 17511/18665 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 -0.14707328538104

Ranking 14040/20870 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
Cabp4 calcium binding protein 4 Mouse Protein Binding 73660 Q8VHC5
Cacna1f calcium channel, voltage-dependent, alpha 1F subunit Mouse Autoregulation 54652 Q9JIS7
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