Human Gene Module / Chromosome 9 / PRUNE2

PRUNE2prune homolog 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 12
Rare Variants / Common Variants
15 / 0
Aliases
PRUNE2, RP11-214N16.3,  A214N16.3,  BMCC1,  BNIPXL,  C9orf65,  KIAA0367,  RP11-58J3.2,  bA214N16.3
Associated Syndromes
-
Chromosome Band
9q21.2
Associated Disorders
ASD, EPS
Relevance to Autism

A rare mutation in the PRUNE2 gene has been identified in a patient with ASD (Vaags et al., 2012).

Molecular Function

May play an important role in regulating differentiation, survival and aggressiveness of tumor cells.

SFARI Genomic Platforms
Reports related to PRUNE2 (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Rare deletions at the neurexin 3 locus in autism spectrum disorder Vaags AK , et al. (2012) Yes -
2 Support Diagnostic exome sequencing in persons with severe intellectual disability de Ligt J , et al. (2012) No Epilepsy, ASD
3 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
4 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
5 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
6 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
7 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
8 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
9 Support De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism Cappi C , et al. (2019) No -
10 Support - Woodbury-Smith M et al. (2022) Yes -
11 Support - Zhou X et al. (2022) Yes -
12 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.7026C>G p.Ile2342Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1659A>C p.Ser553%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.8370T>G p.Ser2790= synonymous_variant De novo - - 31452935 Feliciano P et al. (2019)
c.2167C>T p.Pro723Ser missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.4574C>G p.Ala1525Gly missense_variant De novo - Simplex 31771860 Cappi C , et al. (2019)
c.4226A>G p.Asn1409Ser missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.3737G>A p.Arg1246Lys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.909C>A p.Cys303Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2416G>A p.Glu806Lys missense_variant Familial Both parents - 23033978 de Ligt J , et al. (2012)
c.4810A>T p.Lys1604Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.3173A>G p.Glu1058Gly missense_variant Familial Paternal Multiplex 22209245 Vaags AK , et al. (2012)
c.183dup p.Pro62ThrfsTer4 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2203G>A p.Glu735Lys missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.5088_5089del p.Glu1696AspfsTer15 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.268G>A p.Asp90Asn missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Both inherited and de novo missense variants in the PRUNE2 gene have been identified in ASD probands (Vaags et al., 2012; Cukier et al., 2014; De Rubeis et al., 2014; Iossifov et al., 2014).

Score Delta: Score remained at 2

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
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2

Decreased from 3 to 2

Description

Both inherited and de novo missense variants in the PRUNE2 gene have been identified in ASD probands (Vaags et al., 2012; Cukier et al., 2014; De Rubeis et al., 2014; Iossifov et al., 2014).

1/1/2020
3
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3

Decreased from 3 to 3

Description

Both inherited and de novo missense variants in the PRUNE2 gene have been identified in ASD probands (Vaags et al., 2012; Cukier et al., 2014; De Rubeis et al., 2014; Iossifov et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Both inherited and de novo missense variants in the PRUNE2 gene have been identified in ASD probands (Vaags et al., 2012; Cukier et al., 2014; De Rubeis et al., 2014; Iossifov et al., 2014).

7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Both inherited and de novo missense variants in the PRUNE2 gene have been identified in ASD probands (Vaags et al., 2012; Cukier et al., 2014; De Rubeis et al., 2014; Iossifov et al., 2014).

7/1/2018
icon
4

Increased from to 4

Description

Both inherited and de novo missense variants in the PRUNE2 gene have been identified in ASD probands (Vaags et al., 2012; Cukier et al., 2014; De Rubeis et al., 2014; Iossifov et al., 2014).

Krishnan Probability Score

Score 0.50252161508763

Ranking 1969/25841 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 3.6832162980394E-12

Ranking 17261/18225 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 0.89731775944198

Ranking 6125/18665 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 3

Ranking 355/461 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 -0.012021496981829

Ranking 9066/20870 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.
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