Human Gene Module / Chromosome 16 / PRKCB

PRKCBprotein kinase C beta

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
3 / 4
Aliases
PRKCB, PKC-beta,  PKCB,  PRKCB1,  PRKCB2
Associated Syndromes
-
Chromosome Band
16p12.2-p12.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the PRKCB1 gene and autism in the AGRE cohort (Philippi et al., 2005). However, no association was found between PRKCB1 and autism in the Irish population.

Molecular Function

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PRKCB (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Haplotypes in the gene encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with autism Philippi A , et al. (2005) Yes -
2 Recent Recommendation Polymorphisms of the protein kinase C-beta gene (PRKCB1) accelerate kidney disease in type 2 diabetes without overt proteinuria Araki S , et al. (2006) No -
3 Negative Association Protein kinase C-beta 1 gene variants are not associated with autism in the Irish population Yang MS , et al. (2006) Yes -
4 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
5 Positive Association Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection Pardias AF , et al. (2018) No -
6 Support - Rodin RE et al. (2021) Yes -
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Highly Cited Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats Koya D , et al. (1997) No -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.473G>A p.Arg158His missense_variant De novo - - 33432195 Rodin RE et al. (2021)
c.*5171C>T - 3_prime_UTR_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1748G>A p.Arg583His missense_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
G>T - intergenic_variant - - - 29483656 Pardias AF , et al. (2018)
c.205+54736C>T - intron_variant - - - 16027742 Philippi A , et al. (2005)
c.206-36592A>G - intron_variant - - - 16027742 Philippi A , et al. (2005)
c.206-55346A>G - intron_variant - - - 16027742 Philippi A , et al. (2005)
SFARI Gene score
2

Strong Candidate

There are multiple but inconsistent reports of association with ASD (Philippi et al., 2005 PMID: 16027742; Yang et al., 2007 PMID: 17167344); one report shows decreased expression in postmortem ASD brain.

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.

1/1/2021
2
icon
2

Score remained at 2

Description

There are multiple but inconsistent reports of association with ASD (Philippi et al., 2005 PMID: 16027742; Yang et al., 2007 PMID: 17167344); one report shows decreased expression in postmortem ASD brain.

Reports Added
[The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing2021]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

There are multiple but inconsistent reports of association with ASD (Philippi et al., 2005 PMID: 16027742; Yang et al., 2007 PMID: 17167344); one report shows decreased expression in postmortem ASD brain.

Reports Added
[New Scoring Scheme]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

There are multiple but inconsistent reports of association with ASD (Philippi et al., 2005 PMID: 16027742; Yang et al., 2007 PMID: 17167344); one report shows decreased expression in postmortem ASD brain.

Reports Added
[Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]
7/1/2014
No data
icon
3

Increased from No data to 3

Description

There are multiple but inconsistent reports of association with ASD (Philippi et al., 2005 PMID: 16027742; Yang et al., 2007 PMID: 17167344); one report shows decreased expression in postmortem ASD brain.

4/1/2014
No data
icon
3

Increased from No data to 3

Description

There are multiple but inconsistent reports of association with ASD (Philippi et al., 2005 PMID: 16027742; Yang et al., 2007 PMID: 17167344); one report shows decreased expression in postmortem ASD brain.

Krishnan Probability Score

Score 0.57064184113761

Ranking 889/25841 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 0.99990807001304

Ranking 666/18225 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 0.94273846988867

Ranking 15420/18665 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 3

Ranking 354/461 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 0.5708791378989

Ranking 171/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
C5AR1 complement component 5a receptor 1 Human Protein Modification 728 P21730
CARD11 caspase recruitment domain family, member 11 Mouse Protein Modification 108723 Q8CIS0
CHAT choline O-acetyltransferase Human Protein Modification 1103 P28329
GABRB1 gamma-aminobutyric acid (GABA) A receptor, subunit beta 1 Mouse Protein Modification 14400 P50571
ITGB2 integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) Human Protein Modification 3689 P05107
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