Human Gene Module / Chromosome 11 / PAFAH1B2

PAFAH1B2platelet activating factor acetylhydrolase 1b catalytic subunit 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
4 / 0
Aliases
PAFAH1B2, HEL-S-303
Associated Syndromes
-
Chromosome Band
11q23.3
Associated Disorders
-
Relevance to Autism

Two de novo missense variants and one de novo frameshift variant in the PAFAH1B2 gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017; Du et al., 2019). TADA analysis of 4,504 ASD trios and 3,012 unaffected control/siblings trios from trio-based exome/genome sequencing studies identified PAFAH1B2 as an ASD candidate gene with a q-value < 0.1 (Du et al., 2019).

Molecular Function

Platelet-activating factor acetylhydrolase (PAFAH) inactivates platelet-activating factor (PAF) into acetate and LYSO-PAF. This gene encodes the beta subunit of PAFAH, the other subunits are alpha and gamma.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PAFAH1B2 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Recent Recommendation Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism Du Y , et al. (2019) Yes -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.495T>C p.Tyr165%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.53T>C p.Ile18Thr missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.395C>G p.Ala132Gly missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.390del p.Gln131ArgfsTer20 frameshift_variant De novo - Unknown 31332282 Du Y , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants and one de novo frameshift variant in the PAFAH1B2 gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017; Du et al., 2019). TADA analysis of 4,504 ASD trios and 3,012 unaffected control/siblings trios from trio-based exome/genome sequencing studies identified PAFAH1B2 as an ASD candidate gene with a q-value < 0.1 (Du et al., 2019).

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

Two de novo missense variants and one de novo frameshift variant in the PAFAH1B2 gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017; Du et al., 2019). TADA analysis of 4,504 ASD trios and 3,012 unaffected control/siblings trios from trio-based exome/genome sequencing studies identified PAFAH1B2 as an ASD candidate gene with a q-value < 0.1 (Du et al., 2019).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two de novo missense variants and one de novo frameshift variant in the PAFAH1B2 gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017; Du et al., 2019). TADA analysis of 4,504 ASD trios and 3,012 unaffected control/siblings trios from trio-based exome/genome sequencing studies identified PAFAH1B2 as an ASD candidate gene with a q-value < 0.1 (Du et al., 2019).

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

Increased from to 4

Description

Two de novo missense variants and one de novo frameshift variant in the PAFAH1B2 gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017; Du et al., 2019). TADA analysis of 4,504 ASD trios and 3,012 unaffected control/siblings trios from trio-based exome/genome sequencing studies identified PAFAH1B2 as an ASD candidate gene with a q-value < 0.1 (Du et al., 2019).

Krishnan Probability Score

Score 0.41454694413634

Ranking 21629/25841 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 0.96202947244571

Ranking 2498/18225 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 0.65878315132176

Ranking 935/18665 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 0.23410183414528

Ranking 3705/20870 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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