Human Gene Module / Chromosome 17 / CAMTA2

CAMTA2calmodulin binding transcription activator 2

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
3 / 0
EAGLE Score
2.1
Limited Learn More
Aliases
-
Associated Syndromes
-
Chromosome Band
17p13.2
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

Two rare and potentially damaging de novo missense variants in the CAMTA2 gene have been identified in ASD probands from the SPARK cohort (Zhou et al., 2022), while three protein-truncating variants in this gene were observed in ASD probands, compared to none in controls, from a case-control cohort (Trost et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified CAMTA2 as an ASD-associated gene with a false discovery rate (FDR) < 0.1.

Molecular Function

The protein encoded by this gene is a member of the calmodulin-binding transcription activator protein family. Members of this family share a common domain structure that consists of a transcription activation domain, a DNA-binding domain, and a calmodulin-binding domain. A homozygous 5'UTR variant that was 6 bases upstream of the translation start site of the CAMTA2 gene was found to segregate with disease in a consanguineous extended family with five affected individuals presenting with syndromic tremulous dystonia, spasticity, and white matter disease; transfection of wild type and mutant 5'UTR-linked fluorescent reporters showed a significant reduction in the protein fluorescent activity, implying translation inhibition (Monies et al., 2017).

External Links
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SFARI Genomic Platforms
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Reports related to CAMTA2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Monies D et al. (2017) No -
2 Primary - Zhou X et al. (2022) Yes -
3 Recent Recommendation - Trost B et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3263G>A p.Arg1088Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3362A>G p.Tyr1121Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1764C>T p.Ser588= synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

1/1/2023
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1

Increased from to 1

Krishnan Probability Score

Score 0.4939870580685

Ranking 3882/25841 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 0.99999161372009

Ranking 441/18225 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 0.95056198837852

Ranking 18541/18665 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 0.39324491272858

Ranking 1536/20870 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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