Human Gene Module / Chromosome 7 / PLXNA4

PLXNA4Plexin A4

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
5 / 0
Aliases
PLXNA4, tcag7.1291,  FAYV2820,  PLEXA4,  PLXNA4A,  PLXNA4B,  PRO34003
Associated Syndromes
-
Chromosome Band
7q32.3
Associated Disorders
-
Relevance to Autism

Two novel overlapping CNVs involving the PLXNA4 gene were identified in unrelated ASD cases (Prasad et al., 2012).

Molecular Function

Coreceptor for SEMA3A. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PLXNA4 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism Suda S , et al. (2011) Yes -
2 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
3 Recent Recommendation PlexinA polymorphisms mediate the developmental trajectory of human corpus callosum microstructure Belyk M , et al. (2014) No -
4 Support Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder Krupp DR , et al. (2017) Yes -
5 Support Genome-wide detection of tandem DNA repeats that are expanded in autism Trost B et al. (2020) Yes -
6 Support - Wang J et al. (2023) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - microsatellite Unknown - Simplex 32717741 Trost B et al. (2020)
- - copy_number_gain Familial Maternal Multiplex 23275889 Prasad A , et al. (2013)
- - copy_number_loss Familial Paternal Multiplex 23275889 Prasad A , et al. (2013)
c.3302T>C p.Leu1101Pro missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.5351C>T p.Thr1784Met missense_variant De novo - Simplex 28867142 Krupp DR , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two novel overlapping CNVs involving the PLXNA4 gene were identified in unrelated ASD cases; deletions affecting PLXNA4 were not observed in 0/5,139 controls, whereas duplications affecting this gene were seen in 2/5,139 controls (Prasad et al., 2012). Significantly reduced expression of PLXNA4 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. Polymorphisms in several PlexinA genes, including PLXNA4, were determined to alter the post-natal developmental trajectory of corpus callosum microstructure (PMID 25518740).

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.

7/1/2020
2
icon
2

Score remained at 2

Description

Two novel overlapping CNVs involving the PLXNA4 gene were identified in unrelated ASD cases; deletions affecting PLXNA4 were not observed in 0/5,139 controls, whereas duplications affecting this gene were seen in 2/5,139 controls (Prasad et al., 2012). Significantly reduced expression of PLXNA4 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. Polymorphisms in several PlexinA genes, including PLXNA4, were determined to alter the post-natal developmental trajectory of corpus callosum microstructure (PMID 25518740).

Reports Added
[Genome-wide detection of tandem DNA repeats that are expanded in autism2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two novel overlapping CNVs involving the PLXNA4 gene were identified in unrelated ASD cases; deletions affecting PLXNA4 were not observed in 0/5,139 controls, whereas duplications affecting this gene were seen in 2/5,139 controls (Prasad et al., 2012). Significantly reduced expression of PLXNA4 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. Polymorphisms in several PlexinA genes, including PLXNA4, were determined to alter the post-natal developmental trajectory of corpus callosum microstructure (PMID 25518740).

Reports Added
[New Scoring Scheme]
10/1/2017
3
icon
3

Decreased from 3 to 3

Description

Two novel overlapping CNVs involving the PLXNA4 gene were identified in unrelated ASD cases; deletions affecting PLXNA4 were not observed in 0/5,139 controls, whereas duplications affecting this gene were seen in 2/5,139 controls (Prasad et al., 2012). Significantly reduced expression of PLXNA4 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. Polymorphisms in several PlexinA genes, including PLXNA4, were determined to alter the post-natal developmental trajectory of corpus callosum microstructure (PMID 25518740).

Reports Added
[Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.2017]
7/1/2015
icon
3

Increased from to 3

Description

Two novel overlapping CNVs involving the PLXNA4 gene were identified in unrelated ASD cases; deletions affecting PLXNA4 were not observed in 0/5,139 controls, whereas duplications affecting this gene were seen in 2/5,139 controls (Prasad et al., 2012). Significantly reduced expression of PLXNA4 was observed in the anterior cingulate cortex and primary motor cortex of autistic brains compared to control brains in PMID 21859478. Polymorphisms in several PlexinA genes, including PLXNA4, were determined to alter the post-natal developmental trajectory of corpus callosum microstructure (PMID 25518740).

Krishnan Probability Score

Score 0.49171621656712

Ranking 5187/25841 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 0.9999997021004

Ranking 238/18225 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 0.9494096013089

Ranking 18079/18665 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 0.17952491027888

Ranking 4606/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
DCT L-dopachrome tautomerase Human Protein Binding 1638 P40126
NTRK1 neurotrophic tyrosine kinase, receptor, type 1 Human Protein Binding 4914 P04629
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