Human Gene Module / Chromosome 17 / CACNB1

CACNB1calcium voltage-gated channel auxiliary subunit beta 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
6 / 0
Aliases
CACNB1, CAB1,  CACNLB1,  CCHLB1
Associated Syndromes
-
Chromosome Band
17q12
Associated Disorders
DD/NDD, ADHD, ID
Relevance to Autism

Genome-wide investigation of tandem repeats in 17,231 genomes of families with autism from the Autism Speaks MSSNG project and the Simons Simplex Collection in Trost et al., 2020 identified a rare tandem repeat expansion in the CACNB1 gene (chr17:39182673-39183931 (AAGGAGGAG;AAGAAGGAG)) in seven unrelated ASD probands. This tandem repeat in CACNB1 was observed in more than 0.1% of ASD-affected individuals in this cohort and had a frequency less than 0.1% in unaffected siblings, 1000 Genomes, and 1,612 additional population controls from GTEx and the Mayo Clinic Biobank.

Molecular Function

The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation.

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Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
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SFARI Genomic Platforms
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Reports related to CACNB1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genome-wide detection of tandem DNA repeats that are expanded in autism Trost B et al. (2020) Yes DD, ID, ADHD
2 Support - Despang P et al. (2022) Yes -
3 Support - Viggiano M et al. (2022) Yes DD, ID, epilepsy/seizures
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - microsatellite Unknown - Simplex 32717741 Trost B et al. (2020)
- - microsatellite Unknown - Unknown 32717741 Trost B et al. (2020)
- - microsatellite Unknown - Multiplex 32717741 Trost B et al. (2020)
c.886C>T p.Arg296Cys missense_variant Unknown - - 35122502 Despang P et al. (2022)
c.323A>G p.Asn108Ser missense_variant Familial Paternal - 35350424 Viggiano M et al. (2022)
A>T p.Ile597Asn missense_variant Familial Paternal Multiplex (monozygotic twins) 35350424 Viggiano M et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.57772327648451

Ranking 624/25841 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.
Original Source
ExAC Score

Score 0.99395962249096

Ranking 1607/18225 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
Original Source
Sanders TADA Score

Score 0.94130341467339

Ranking 14883/18665 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).
Original Source
Zhang D Score

Score 0.24627320149294

Ranking 3525/20870 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.
Original Source
CNVs associated with CACNB1(1 CNVs)
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17q12 77 Deletion-Duplication 117  /  510
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