Human Gene Module / Chromosome 3 / PLXNB1

PLXNB1plexin B1

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
5 / 0
Aliases
PLXNB1, PLEXIN-B1,  PLXN5,  SEP
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
3p21.31
Associated Disorders
-
Relevance to Autism

A de novo loss-of-function (LoF) variant in the PLXNB1 gene was first identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). A second ASD-associated de novo LOF variant was identified in a proband from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Molecular Function

Receptor for SEMA4D. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.

Reports related to PLXNB1 (3 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 The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Recent Recommendation Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.4318C>T p.Pro1440Ser stop_gained De novo NA - 28191889 Stessman HA , et al. (2017)
c.1148C>T p.Pro383Leu missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.3665G>T p.Arg1222Leu missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.3091C>T p.Arg1031Cys missense_variant De novo NA Simplex 28191889 Stessman HA , et al. (2017)
c.4334del p.Leu1445ArgfsTer75 frameshift_variant De novo NA - 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo loss-of-function (LoF) variant in the PLXNB1 gene was first identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). A second ASD-associated de novo LOF variant was identified in a proband from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Score Delta: Score remained at 3

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

A de novo loss-of-function (LoF) variant in the PLXNB1 gene was first identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). A second ASD-associated de novo LOF variant was identified in a proband from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

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

Increased from to 3

Description

A de novo loss-of-function (LoF) variant in the PLXNB1 gene was first identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). A second ASD-associated de novo LOF variant was identified in a proband from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Krishnan Probability Score

Score 0.49627293991465

Ranking 2639/25841 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.
ExAC Score

Score 0.85019510818446

Ranking 3617/18225 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
Sanders TADA Score

Score 0.55484507243386

Ranking 577/18665 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).
Zhang D Score

Score -0.15992128911156

Ranking 14429/20870 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.
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