Human Gene Module / Chromosome 9 / PNPLA7

PNPLA7patatin like phospholipase domain containing 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
11 / 0
Aliases
PNPLA7, C9orf111,  NTE-R1,  NTEL1
Associated Syndromes
-
Chromosome Band
9q34.3
Associated Disorders
-
Relevance to Autism

Two de novo variants in the PLPNA7 gene (one loss-of-function, one predicted damaging missense) were identified in ASD probands from the Simons Simplex Collection (ORoak et al., 2012; Iossifov et al., 2014). TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified PNPLA7 as an ASD risk gene with a false discovery rate (FDR) < 0.1; among the de novo variants associated with this gene in ASD subjects as a loss-of-function variant, a predicted damaging (Mis3) missense variant, and a splicing SNV.

Molecular Function

Human patatin-like phospholipases, such as PNPLA7, have been implicated in regulation of adipocyte differentiation and have been induced by metabolic stimuli. Serine hydrolase, whose specific chemical modification by certain organophosphorus (OP) compounds leads to distal axonopathy.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PNPLA7 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Recent Recommendation A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies Liu Y , et al. (2018) Yes -
4 Support - Woodbury-Smith M et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - missense_variant De novo - - 29754769 Liu Y , et al. (2018)
- - splicing_variant De novo - - 29754769 Liu Y , et al. (2018)
- - loss_of_function_variant De novo - - 29754769 Liu Y , et al. (2018)
c.1876C>T p.Arg626Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1876C>T p.Arg626Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.3148C>T p.Gln1050Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.795G>A p.Pro265%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1527G>A p.Thr509%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3397A>C p.Ser1133Arg missense_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.3795C>T p.Ala1265%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2673_2674insCGTG p.Glu892ArgfsTer107 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo variants in the PLPNA7 gene (one loss-of-function, one predicted damaging missense) were identified in ASD probands from the Simons Simplex Collection (ORoak et al., 2012; Iossifov et al., 2014). TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified PNPLA7 as an ASD risk gene with a false discovery rate (FDR) < 0.1; among the de novo variants associated with this gene in ASD subjects as a loss-of-function variant, a predicted damaging (Mis3) missense variant, and a splicing SNV.

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 variants in the PLPNA7 gene (one loss-of-function, one predicted damaging missense) were identified in ASD probands from the Simons Simplex Collection (ORoak et al., 2012; Iossifov et al., 2014). TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified PNPLA7 as an ASD risk gene with a false discovery rate (FDR) < 0.1; among the de novo variants associated with this gene in ASD subjects as a loss-of-function variant, a predicted damaging (Mis3) missense variant, and a splicing SNV.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two de novo variants in the PLPNA7 gene (one loss-of-function, one predicted damaging missense) were identified in ASD probands from the Simons Simplex Collection (ORoak et al., 2012; Iossifov et al., 2014). TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified PNPLA7 as an ASD risk gene with a false discovery rate (FDR) < 0.1; among the de novo variants associated with this gene in ASD subjects as a loss-of-function variant, a predicted damaging (Mis3) missense variant, and a splicing SNV.

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

Increased from to 4

Description

Two de novo variants in the PLPNA7 gene (one loss-of-function, one predicted damaging missense) were identified in ASD probands from the Simons Simplex Collection (ORoak et al., 2012; Iossifov et al., 2014). TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified PNPLA7 as an ASD risk gene with a false discovery rate (FDR) < 0.1; among the de novo variants associated with this gene in ASD subjects as a loss-of-function variant, a predicted damaging (Mis3) missense variant, and a splicing SNV.

Krishnan Probability Score

Score 0.44513653863059

Ranking 15555/25841 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 6.2282367015855E-27

Ranking 18123/18225 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 0.47837842880208

Ranking 404/18665 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 -0.34612000234184

Ranking 17785/20870 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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