Human Gene Module / Chromosome 19 / CAPN12

CAPN12Calpain 12

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
37 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19q13.2
Associated Disorders
-
Relevance to Autism

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Molecular Function

The protein encoded by this gene is a calcium-regulated non-lysosomal thiol-protease with broad endoepeptidase specificy.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CAPN12 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Primary Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
4 Support Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability Riazuddin S , et al. (2016) No -
5 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (37)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1879-48C>G - intron_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.766G>A p.Val256Ile missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.514C>T p.Gln172Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.426+1G>A - splice_site_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1025C>T p.Pro342Leu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.329C>A p.Ala110Asp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.334G>A p.Ala112Thr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.355C>T p.Arg119Trp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.518G>A p.Arg173Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.568G>A p.Gly190Ser missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.613G>A p.Val205Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.629G>C p.Gly210Ala missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.631G>A p.Val211Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.685C>T p.Arg229Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.791C>T p.Thr264Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.899G>A p.Arg300His missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.926G>A p.Arg309His missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1016C>T p.Ser339Leu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1999C>T p.Arg667Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.804+2T>C - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.422T>C p.Phe141Ser missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.518G>A p.Arg173Gln missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.551C>T p.Ala184Val missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.704A>T p.Glu235Val missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.779C>T p.Ala260Val missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.514C>T p.Gln172Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1879-2A>G - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1147C>T p.Pro383Ser missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.648_651del p.Tyr216Ter frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.660del p.Asn220LysfsTer24 frameshift_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.660del p.Asn220LysfsTer24 frameshift_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.660_661del p.Asn220LysfsTer25 frameshift_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.658_661del p.Asn220AlafsTer23 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.293_294del p.Cys98SerfsTer6 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.658_659del p.Asn220GlnfsTer25 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.658_659del p.Asn220GlnfsTer25 frameshift_variant Familial Both parents Multiplex 27457812 Riazuddin S , et al. (2016)
c.1442_1443insAGCGGTCGGCGCGC p.Pro482AlafsTer13 frameshift_variant Unknown Not paternal Simplex 30675382 Leblond CS , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
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

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

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

Decreased from 4 to 4

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
1/1/2019
4
icon
4

Decreased from 4 to 4

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Reports Added
[Both rare and common genetic variants contribute to autism in the Faroe Islands.2019]
7/1/2016
4
icon
4

Decreased from 4 to 4

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Reports Added
[Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.2016]
10/1/2015
icon
4

Increased from to 4

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Krishnan Probability Score

Score 0.4457496043243

Ranking 15229/25841 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 7.4795676771931E-20

Ranking 17966/18225 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 0.070313880421879

Ranking 54/18665 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 0.015666090732828

Ranking 8207/20870 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
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