PRUNE2prune homolog 2
Autism Reports / Total Reports
9 / 12Rare Variants / Common Variants
15 / 0Aliases
PRUNE2, RP11-214N16.3, A214N16.3, BMCC1, BNIPXL, C9orf65, KIAA0367, RP11-58J3.2, bA214N16.3Associated Syndromes
-Chromosome Band
9q21.2Associated Disorders
ASD, EPSRelevance 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.
External Links
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
criteria met
See SFARI Gene'scoring criteriaWe 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
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
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
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
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
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.