Human Gene Module / Chromosome 1 / PTGS2

PTGS2prostaglandin-endoperoxide synthase 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 8
Rare Variants / Common Variants
2 / 1
Aliases
PTGS2, COX-2,  COX2,  GRIPGHS,  PGG/HS,  PGHS-2,  PHS-2,  hCox-2
Associated Syndromes
-
Chromosome Band
1q31.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the PTGS2 gene and autism in a Korean population cohort (Yoo et al., 2008).

Molecular Function

The encoded protein is a key enzyme for prostaglandin synthesis. It has prostagl andin-endoperoxide synthase activity.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PTGS2 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Contribution of inducible nitric oxide synthase and cyclooxygenase-2 to apoptosis induction in smooth chorion trophoblast cells of human fetal membrane tissues Yuan B , et al. (2006) No -
2 Recent Recommendation PGE2 glycerol ester, a COX-2 oxidative metabolite of 2-arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neurons Sang N , et al. (2006) No -
3 Primary Association between PTGS2 polymorphism and autism spectrum disorders in Korean trios Yoo HJ , et al. (2008) Yes -
4 Recent Recommendation Autism-related behaviors in the cyclooxygenase-2-deficient mouse model Wong CT , et al. (2018) No -
5 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Highly Cited COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex Kaufmann WE , et al. (1996) No -
8 Highly Cited Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2) Oshima M , et al. (1996) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1731C>T p.Val577= synonymous_variant De novo - - 31452935 Feliciano P et al. (2019)
c.1613_1615del p.Gly538del inframe_deletion De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.52+150T>C - intron_variant - - - 18579107 Yoo HJ , et al. (2008)
SFARI Gene score
2

Strong Candidate

Genetic association has been found between the PTGS2 gene and autism in a Korean population cohort (Yoo et al., 2008). PTGS2 knockout mice were found to display autism-related behaviors, including increased repetitive behaviors in both young and adult male and female mice and abnormal social behavior in adult female mice (Wong et al., 2018).

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

Genetic association has been found between the PTGS2 gene and autism in a Korean population cohort (Yoo et al., 2008). PTGS2 knockout mice were found to display autism-related behaviors, including increased repetitive behaviors in both young and adult male and female mice and abnormal social behavior in adult female mice (Wong et al., 2018).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Genetic association has been found between the PTGS2 gene and autism in a Korean population cohort (Yoo et al., 2008). PTGS2 knockout mice were found to display autism-related behaviors, including increased repetitive behaviors in both young and adult male and female mice and abnormal social behavior in adult female mice (Wong et al., 2018).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2018
4
icon
4

Decreased from 4 to 4

Description

Genetic association has been found between the PTGS2 gene and autism in a Korean population cohort (Yoo et al., 2008). PTGS2 knockout mice were found to display autism-related behaviors, including increased repetitive behaviors in both young and adult male and female mice and abnormal social behavior in adult female mice (Wong et al., 2018).

Reports Added
[Autism-related behaviors in the cyclooxygenase-2-deficient mouse model.2018]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

A single, unreplicated association has been reported.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A single, unreplicated association has been reported.

Krishnan Probability Score

Score 0.4951407332165

Ranking 3176/25841 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 0.99903311598439

Ranking 1060/18225 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 0.92959948801811

Ranking 11209/18665 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 429/461 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 0.40531076566429

Ranking 1396/20870 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
MIR101-1 microRNA 101-1 Human Direct Regulation 406893
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