Human Gene Module / Chromosome 1 / TRIM33

TRIM33Tripartite motif containing 33

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
0 / 4
Aliases
TRIM33, ECTO,  PTC7,  RFG7,  TF1G,  TIF1G,  TIF1GAMMA,  TIFGAMMA
Associated Syndromes
-
Genetic Category
Genetic Association
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.

Reports related to TRIM33 (1 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 -
Rare Variants  

No rare variants reported.

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
3

Suggestive Evidence

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 4

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.

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
Submit New Gene

Report an Error

SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
Close