Human Gene Module / Chromosome 20 / PLCB1

PLCB1phospholipase C, beta 1 (phosphoinositide-specific)

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 9
Rare Variants / Common Variants
16 / 0
Aliases
PLCB1, RP4-654A7.1,  EIEE12,  PI-PLC,  PLC-154,  PLC-I,  PLC154,  PLCB1A,  PLCB1B
Associated Syndromes
-
Chromosome Band
20p12.3
Associated Disorders
DD/NDD
Relevance to Autism

A rare deletion of the PLCB1 gene was found in an individual with ASD (Christian et al., 2008). Biallelic loss-of-function variants in this gene have also been identified in individuals with early-onset epileptic encephalopathy (Kurian et al., 2010; Poduri et al., 2012; Ngoh et al., 2014).

Molecular Function

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PLCB1 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder Christian SL , et al. (2008) Yes -
2 Support Phospholipase C beta 1 deficiency is associated with early-onset epileptic encephalopathy Kurian MA , et al. (2010) No -
3 Support Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy Poduri A , et al. (2012) No -
4 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
5 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
6 Support Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum Ngoh A , et al. (2014) No DD
7 Support Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease Karaca E , et al. (2015) No -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Wang J et al. (2023) Yes -
Rare Variants   (16)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial - - 18374305 Christian SL , et al. (2008)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Familial Maternal Simplex 24684524 Ngoh A , et al. (2014)
c.1015C>A p.Gln339Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3423+11864C>A - missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
- - copy_number_gain Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Both parents Simplex 22690784 Poduri A , et al. (2012)
- - copy_number_loss Familial Both parents Simplex 20833646 Kurian MA , et al. (2010)
- - copy_number_gain Familial Maternal Multiplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Multiplex 23375656 Girirajan S , et al. (2013)
c.2279G>A p.Arg760His missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.99+1G>A - splice_site_variant Familial Paternal Simplex 24684524 Ngoh A , et al. (2014)
c.2207dup p.Val737GlyfsTer15 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2179T>A p.Trp727Arg missense_variant Familial Both parents Multiplex 26539891 Karaca E , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Copy number variants affecting the PLCB1 gene have been identified in ASD cases (PMIDs 18374305, 23275889, 23375656). Biallelic variants of this gene are associated with early infantile epileptic encephalopathy-12 (EIEE12; OMIM 613722) (PMIDs 20833646, 22690784).

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
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Copy number variants affecting the PLCB1 gene have been identified in ASD cases (PMIDs 18374305, 23275889, 23375656). Biallelic variants of this gene are associated with early infantile epileptic encephalopathy-12 (EIEE12; OMIM 613722) (PMIDs 20833646, 22690784).

Reports Added
[New Scoring Scheme]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

Copy number variants affecting the PLCB1 gene have been identified in ASD cases (PMIDs 18374305, 23275889, 23375656). Biallelic variants of this gene are associated with early infantile epileptic encephalopathy-12 (EIEE12; OMIM 613722) (PMIDs 20833646, 22690784).

Reports Added
[Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder.2008] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Phospholipase C beta 1 deficiency is associated with early-onset epileptic encephalopathy.2010] [Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy.2012] [Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum.2014] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015]
7/1/2015
icon
3

Increased from to 3

Description

Copy number variants affecting the PLCB1 gene have been identified in ASD cases (PMIDs 18374305, 23275889, 23375656). Biallelic variants of this gene are associated with early infantile epileptic encephalopathy-12 (EIEE12; OMIM 613722) (PMIDs 20833646, 22690784).

Krishnan Probability Score

Score 0.63393481694933

Ranking 61/25841 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 0.97904481609408

Ranking 2167/18225 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 0.33533728601935

Ranking 209/18665 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 0.32070992943914

Ranking 2423/20870 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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