Human Gene Module / Chromosome 9 / TRIM32

TRIM32tripartite motif containing 32

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
12 / 0
Aliases
TRIM32, BBS11,  HT2A,  LGMD2H,  LGMDR8,  TATIP
Associated Syndromes
-
Chromosome Band
9q33.1
Associated Disorders
DD/NDD, ADHD, ID, EPS
Relevance to Autism

Screening of 9q33.1 copy number variants disrupting ASTN2 or both ASTN2 and TRIM32 in clinical microarray data from 89,986 individuals across 10 sites, including 64,114 subjects with neurodevelopmental disorders (NDD), in Lionel et al., 2014 found that deletions affecting both ASTN2 and TRIM32 were statistically enriched in NDD cases compared to controls (23 deletions in 64,114 cases vs. 6 in 44,085 controls; P-value 0.019); this enrichment was subsequently determined to be male-specific [22 deletions in 40,438 NDD males vs. 2 deletions in 14,953 male controls (P-value 0.024) compared to 1 deletion in 23.676 NDD females vs. 3 deletions in 18.218 female controls (P-value 0.964)]. Zhu et al., 2019 found that absence of TRIM32 resulted in impaired generation of GABAergic interneurons and autism-like behaviors in mice via suppressed mTOR signaling.

Molecular Function

The protein encoded by this gene is a member of the tripartite motif (TRIM) family and has an E3 ubiquitin ligase activity. The protein localizes to cytoplasmic bodies and has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TRIM32 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes Lionel AC , et al. (2014) Yes ADHD, DD, ID, epilepsy, OCD
2 Primary Absence of TRIM32 Leads to Reduced GABAergic Interneuron Generation and Autism-like Behaviors in Mice via Suppressing mTOR Signaling Zhu JW , et al. (2019) Yes -
3 Support Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use Husson T , et al. (2020) Yes -
4 Support - Sun YY et al. (2022) No -
5 Support - Baccino-Calace M et al. (2022) No -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Unknown - - 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Unknown - Simplex 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal - 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Paternal - 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Unknown - Multiplex 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Simplex 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Paternal Simplex 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Multiplex 32094338 Husson T , et al. (2020)
- - copy_number_loss Familial Maternal Multiplex 24381304 Lionel AC , et al. (2014)
- p.Arg201Cys missense_variant Familial Paternal - 24381304 Lionel AC , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.4474782184425

Ranking 12319/25841 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 0.097317643527322

Ranking 7890/18225 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 0.94123818976334

Ranking 14859/18665 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 0.51088684425408

Ranking 437/20870 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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