Human Gene Module / Chromosome 7 / PDE1C

PDE1Cphosphodiesterase 1C

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
2 / 1
Aliases
PDE1C, Hcam3,  cam-PDE 1C,  hCam-3
Associated Syndromes
-
Chromosome Band
7p14.3
Associated Disorders
-
Relevance to Autism

An intronic SNP in the PDE1C gene was found to associate with ASD (P-value < 1.0E-04) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium 2017). Inherited missense variants in the PDE1C gene have been identified in ASD probands in two reports (Vaags et al., 2012; Krupp et al., 2017).

Molecular Function

Cyclic nucleotide phosphodiesterases (PDEs) catalyze hydrolysis of the cyclic nucleotides cAMP and cGMP to the corresponding nucleoside 5-prime-monophosphates. Members of the PDE1 family, such as PDE1C, are calmodulin-dependent PDEs (CaM-PDEs) that are stimulated by a calcium-calmodulin complex.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PDE1C (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Rare deletions at the neurexin 3 locus in autism spectrum disorder Vaags AK , et al. (2012) Yes -
2 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 -
3 Support Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder Krupp DR , et al. (2017) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1773C>A p.Asn591Lys missense_variant Familial Maternal Simplex 28867142 Krupp DR , et al. (2017)
c.181C>G p.Leu61Val missense_variant Familial Paternal Multiplex 22209245 Vaags AK , et al. (2012)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1892-4045A>G;c.1891+14727A>G;c.2071+14727A>G;c.2072-4045A>G;c.2297-4045A>G;c.1894+14727A>G;c.1864+ - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
2

Strong Candidate

An intronic SNP in the PDE1C gene was found to associate with ASD (P-value < 1.0E-04) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium 2017). Inherited missense variants in the PDE1C gene have been identified in ASD probands in two reports (Vaags et al., 2012; Krupp et al., 2017).

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

An intronic SNP in the PDE1C gene was found to associate with ASD (P-value < 1.0E-04) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium 2017). Inherited missense variants in the PDE1C gene have been identified in ASD probands in two reports (Vaags et al., 2012; Krupp et al., 2017).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

An intronic SNP in the PDE1C gene was found to associate with ASD (P-value < 1.0E-04) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium 2017). Inherited missense variants in the PDE1C gene have been identified in ASD probands in two reports (Vaags et al., 2012; Krupp et al., 2017).

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

An intronic SNP in the PDE1C gene was found to associate with ASD (P-value < 1.0E-04) in a GWAS meta-analysis of 7387 ASD cases and 8567 controls (Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium 2017). Inherited missense variants in the PDE1C gene have been identified in ASD probands in two reports (Vaags et al., 2012; Krupp et al., 2017).

Krishnan Probability Score

Score 0.56679970180238

Ranking 1202/25841 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 0.0002707038758473

Ranking 12558/18225 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 0.91105838462853

Ranking 7672/18665 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
Larsen Cumulative Evidence Score

Score 0

Ranking 453/461 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.
Original Source
Zhang D Score

Score 0.01301001329553

Ranking 8269/20870 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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