Human Gene Module / Chromosome 15 / ANP32A

ANP32Aacidic nuclear phosphoprotein 32 family member A

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
3 / 0
EAGLE Score
3.1
Limited Learn More
Aliases
-
Associated Syndromes
-
Chromosome Band
15q23
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Functional
Relevance to Autism

Two de novo loss-of-function (LoF) variants in the ANP32A gene have been identified in ASD probands from the Simons Simplex Collection and the MSSNG cohort (Satterstrom et al., 2020; Zhou et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified ANP32A as an ASD-associated gene with a false discovery rate (FDR) < 0.1.

Molecular Function

Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking (Seo et al., 2002).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ANP32A (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Seo SB et al. (2002) No -
2 Primary Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Recent Recommendation - Trost B et al. (2022) Yes -
5 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.431_432del p.Tyr144SerfsTer5 frameshift_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.695_698del p.Glu232GlyfsTer24 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.90_105del p.Asn30LysfsTer13 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

1/1/2023
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.56907776619573

Ranking 1063/25841 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 0.97387003585671

Ranking 2276/18225 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 0.91296417709314

Ranking 7943/18665 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 0.34317325155844

Ranking 2104/20870 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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