Human Gene Module / Chromosome 7 / SERPINE1

SERPINE1serpin family E member 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
1 / 1
Aliases
SERPINE1, PAI,  PAI-1,  PAI1,  PLANH1
Associated Syndromes
-
Chromosome Band
7q22.1
Associated Disorders
-
Relevance to Autism

FBAT analysis of a 664-family ASD sample revealed association with ASD diagnosis of the C allele at rs13238709, a marker 3' to the SERPINE1 gene (P=0.048) (Campbell et al., 2008). However, no association between the 4G/5G polymorphism of the SERPINE1 gene promoter and autistic disorder was observed in Persico et al., 2001.

Molecular Function

This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SERPINE1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Negative Association No association between the 4g/5G polymorphism of the plasminogen activator inhibitor-1 gene promoter and autistic disorder Persico AM , et al. (2001) Yes -
2 Primary Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder Campbell DB , et al. (2009) Yes -
3 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.308A>G p.Lys103Arg missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- C/T downstream_gene_variant - - - 19360663 Campbell DB , et al. (2009)
SFARI Gene score
2

Strong Candidate

FBAT analysis of a 664-family ASD sample revealed association with ASD diagnosis of the C allele at rs13238709, a marker 3' to the SERPINE1 gene (P=0.048) (Campbell et al., 2008). However, no association between the 4G/5G polymorphism of the SERPINE1 gene promoter and autistic disorder was observed in Persico et al., 2001.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

FBAT analysis of a 664-family ASD sample revealed association with ASD diagnosis of the C allele at rs13238709, a marker 3' to the SERPINE1 gene (P=0.048) (Campbell et al., 2008). However, no association between the 4G/5G polymorphism of the SERPINE1 gene promoter and autistic disorder was observed in Persico et al., 2001.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

FBAT analysis of a 664-family ASD sample revealed association with ASD diagnosis of the C allele at rs13238709, a marker 3' to the SERPINE1 gene (P=0.048) (Campbell et al., 2008). However, no association between the 4G/5G polymorphism of the SERPINE1 gene promoter and autistic disorder was observed in Persico et al., 2001.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

FBAT analysis of a 664-family ASD sample revealed association with ASD diagnosis of the C allele at rs13238709, a marker 3' to the SERPINE1 gene (P=0.048) (Campbell et al., 2008). However, no association between the 4G/5G polymorphism of the SERPINE1 gene promoter and autistic disorder was observed in Persico et al., 2001.

Krishnan Probability Score

Score 0.43215361933812

Ranking 20720/25841 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 0.21951997696725

Ranking 6924/18225 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 0.94003180776342

Ranking 14421/18665 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
Larsen Cumulative Evidence Score

Score 1

Ranking 433/461 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.
Original Source
Zhang D Score

Score -0.06796983209501

Ranking 11105/20870 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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