Human Gene Module / Chromosome 19 / PRKD2

PRKD2protein kinase D2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
4 / 0
Aliases
PRKD2, HSPC187,  PKD2,  nPKC-D2
Associated Syndromes
-
Chromosome Band
19q13.32
Associated Disorders
-
Relevance to Autism

De novo missense variants in the PRKD2 gene were identified in two ASD probands (De Rubeis et al., 2014; Hashimoto et al., 2016); functional analysis in Matsumura et al., 2019 demonstrated that both ASD-associated missense variants caused statistically significant decreases in PKD2 autophosphorylation and ERK1/2 phosphorylation.

Molecular Function

The protein encoded by this gene belongs to the protein kinase D (PKD) family of serine/threonine protein kinases. This kinase can be activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells. It can bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral membrane protein exit from TGN.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PRKD2 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder Hashimoto R , et al. (2015) Yes -
3 Recent Recommendation Autism-associated protein kinase D2 regulates embryonic cortical neuron development Matsumura K , et al. (2019) No -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1928A>C p.Lys643Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2122C>T p.Arg708Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.694C>T p.Arg232Cys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.548G>A p.Ser183Asn missense_variant De novo - Simplex 26582266 Hashimoto R , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo missense variants in the PRKD2 gene were identified in two ASD probands (De Rubeis et al., 2014; Hashimoto et al., 2016); functional analysis in Matsumura et al., 2019 demonstrated that both ASD-associated missense variants caused statistically significant decreases in PKD2 autophosphorylation and ERK1/2 phosphorylation.

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.

10/1/2019
icon
2

Increased from to 2

New Scoring Scheme
Description

De novo missense variants in the PRKD2 gene were identified in two ASD probands (De Rubeis et al., 2014; Hashimoto et al., 2016); functional analysis in Matsumura et al., 2019 demonstrated that both ASD-associated missense variants caused statistically significant decreases in PKD2 autophosphorylation and ERK1/2 phosphorylation.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.49133294375758

Ranking 5637/25841 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 0.9996964074254

Ranking 840/18225 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 0.68980195562139

Ranking 1095/18665 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 0.10616040282985

Ranking 5998/20870 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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