Human Gene Module / Chromosome 3 / PLXNB1

PLXNB1plexin B1

Score
3
Suggestive Evidence Criteria 3.1
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.Arg1440Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.1148C>T p.Pro383Leu missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.3665G>T p.Arg1222Leu missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.3091C>T p.Arg1031Cys missense_variant De novo - Simplex 28191889 Stessman HA , et al. (2017)
c.4334del p.Leu1445ArgfsTer75 frameshift_variant De novo - - 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

3

Score Delta: Score remained at 3.3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

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.
CNVs associated with PLXNB1(1 CNVs)
3p21.31 14 Deletion-Duplication 28  /  59
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