Human Gene Module / Chromosome 1 / TRIM33

TRIM33Tripartite motif containing 33

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
1 / 4
Aliases
TRIM33, ECTO,  PTC7,  RFG7,  TF1G,  TIF1G,  TIF1GAMMA,  TIFGAMMA
Associated Syndromes
-
Chromosome Band
1p13.2
Associated Disorders
-
Relevance to Autism

Meta-analysis of two discovery cohorts of Chinese descent and three replication cohorts of European descent identified a non-synonymous SNP located in the TRIM33 gene (rs6537835) that showed significant association with ASD (P=3.26E-08) (Xia et al., 2013); significant differential expression of TRIM33 in the brains of ASD cases compared to controls was also observed in this report.

Molecular Function

Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation.

SFARI Genomic Platforms
Reports related to TRIM33 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Common genetic variants on 1p13.2 associate with risk of autism Xia K , et al. (2013) Yes -
2 Support - Wang J et al. (2023) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.371C>T p.Thr124Ile missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
T/C - intergenic_variant - - - 24189344 Xia K , et al. (2013)
minor allele, C - intergenic_variant - - - 24189344 Xia K , et al. (2013)
c.526+464G>T minor allele, A intron_variant - - - 24189344 Xia K , et al. (2013)
c.2519T>C;c.2591T>C p.Ile840Thr;p.Ile864Thr missense_variant - - - 24189344 Xia K , et al. (2013)
SFARI Gene score
2

Strong Candidate

Meta-analysis of two discovery cohorts of Chinese descent and three replication cohorts of European descent identified a non-synonymous SNP located in the TRIM33 gene (rs6537835) that showed significant association with ASD (P=3.26E-08) (Xia et al., 2013); significant differential expression of TRIM33 in the brains of ASD cases compared to controls was also observed in this report.

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
icon
2

Decreased from 3 to 2

Description

Meta-analysis of two discovery cohorts of Chinese descent and three replication cohorts of European descent identified a non-synonymous SNP located in the TRIM33 gene (rs6537835) that showed significant association with ASD (P=3.26E-08) (Xia et al., 2013); significant differential expression of TRIM33 in the brains of ASD cases compared to controls was also observed in this report.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Meta-analysis of two discovery cohorts of Chinese descent and three replication cohorts of European descent identified a non-synonymous SNP located in the TRIM33 gene (rs6537835) that showed significant association with ASD (P=3.26E-08) (Xia et al., 2013); significant differential expression of TRIM33 in the brains of ASD cases compared to controls was also observed in this report.

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

Meta-analysis of two discovery cohorts of Chinese descent and three replication cohorts of European descent identified a non-synonymous SNP located in the TRIM33 gene (rs6537835) that showed significant association with ASD (P=3.26E-08) (Xia et al., 2013); significant differential expression of TRIM33 in the brains of ASD cases compared to controls was also observed in this report.

Krishnan Probability Score

Score 0.57312016956627

Ranking 692/25841 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 0.99999835593446

Ranking 339/18225 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 0.93982721848633

Ranking 14348/18665 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 10

Ranking 194/461 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 0.64284243948802

Ranking 22/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ACY1 Aminoacylase-1 Human Protein Binding 95 Q03154
ZIM2 Zinc finger imprinted 2 Human Protein Binding 23619 Q9NZV7
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