Human Gene Module / Chromosome 19 / PLAUR

PLAURPlasminogen activator, urokinase receptor

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
1 / 1
Aliases
PLAUR, CD87,  U-PAR,  UPAR,  URKR
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
19q13.31
Associated Disorders
-
Relevance to Autism

The PLAUR promoter variant rs344781 T allele was associated with ASD by both family-based association tests (P=0.006) and case-control analyses (P=0.007) in an association study of genes encoding proteins that regulate MET expression and activity in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls (Campbell et al., 2008).

Molecular Function

This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. PLAUR is expressed in neurons of the rolandic area of the brain (at protein level).

Reports related to PLAUR (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Campbell DB , et al. (2009) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.109G>T p.Glu37Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-516G>A C/T 2KB_upstream_variant - - - 19360663 Campbell DB , et al. (2009)
SFARI Gene score
3

Suggestive Evidence

The PLAUR promoter variant rs344781 T allele was associated with ASD by both family-based association tests (P=0.006) and case-control analyses (P=0.007) in an association study of genes encoding proteins that regulate MET expression and activity in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls (Campbell et al., 2008).

Score Delta: Score remained at 4

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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

The PLAUR promoter variant rs344781 T allele was associated with ASD by both family-based association tests (P=0.006) and case-control analyses (P=0.007) in an association study of genes encoding proteins that regulate MET expression and activity in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls (Campbell et al., 2008).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

The PLAUR promoter variant rs344781 T allele was associated with ASD by both family-based association tests (P=0.006) and case-control analyses (P=0.007) in an association study of genes encoding proteins that regulate MET expression and activity in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls (Campbell et al., 2008).

4/1/2018
icon
4.3

Increased from to 4.3

Description

4

Krishnan Probability Score

Score 0.49389411204925

Ranking 3929/25841 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 0.3065849263056

Ranking 6476/18225 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 0.92274891642016

Ranking 9636/18665 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).
Larsen Cumulative Evidence Score

Score 5

Ranking 289/461 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.
Zhang D Score

Score 0.1570662652928

Ranking 5025/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ARSA Arylsulfatase A Human Protein Binding 410 P15289
BMP8B ESRRB Human Protein Binding 656 P34820
CNTNAP3B Contactin-associated protein-like 3B Human Protein Binding Q96NU0
CTSA cathepsin A Human Protein Binding 5476 P10619
DDX11L8 Putative ATP-dependent RNA helicase DDX11-like protein 8 Human Protein Binding A8MPP1
FBLN5 fibulin 5 Human Protein Binding 10516 Q9UBX5
GALNS N-acetylgalactosamine-6-sulfatase Human Protein Binding 2588 P34059
ITGAM integrin, alpha M (complement component 3 receptor 3 subunit) Human Protein Binding 3684 P11215
KNG1 kininogen 1 Human Protein Binding 3827 P01042
LOXL2 Lysyl oxidase homolog 2 Human Protein Binding 4017 Q9Y4K0
Mmp12 matrix metallopeptidase 12 Mouse Protein Modification 17381 P34960
NAGLU N-acetylglucosaminidase, alpha Human Protein Binding 4669 P54802
PCSK5 Proprotein convertase subtilisin/kexin type 5 Human Protein Binding 5125 Q92824
PLTP Phospholipid transfer protein Human Protein Binding 5360 P55058-2
POGLUT1 Protein O-glucosyltransferase 1 Human Protein Binding 56983 Q8NBL1
ST3GAL4 CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4 Human Protein Binding 6484 Q11206-2
TXNDC16 Thioredoxin domain-containing protein 16 Human Protein Binding 57544 Q9P2K2
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