Human Gene Module / Chromosome 10 / TRIM8

TRIM8tripartite motif containing 8

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
18 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
10q24.32
Associated Disorders
-
Relevance to Autism

A de novo loss-of-function variant and two de novo missense variants in the TRIM8 gene have been identified in ASD probands (Takata et al., 2018; Zhou et al., 2022; Miyake et al., 2023). Heterozygous variants in the TRIM8 gene are responsible for focal segmental glomerulosclerosis and neurodevelopmental syndrome (FSGSNEDS; OMIM 619428), a disorder characterized by global developmental delay, renal dysfunction manifesting as proteinuria and nephrotic syndrome apparent from infancy or early childhood, and variable neurodevelopmental features; autism spectrum disorder, autistic features, and/or stereotypy has been reported in a subset of affected individuals (Assoum et al., 2018; Weng et al., 2021).

Molecular Function

This gene encodes a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, the encoded protein is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
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Reports related to TRIM8 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
2 Support - Assoum M et al. (2018) No ASD, ID, stereotypy
3 Support - Weng PL et al. (2021) No ASD
4 Support - Zhou X et al. (2022) Yes -
5 Primary - Miyake N et al. (2023) Yes -
Rare Variants   (18)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1231C>T p.Gln411Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1240C>T p.Gln414Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1267C>T p.Gln423Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1333C>T p.Gln445Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1375C>T p.Gln459Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1380T>A p.Tyr460Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1380T>G p.Tyr460Ter stop_gained Unknown - - 33508234 Weng PL et al. (2021)
c.80A>G p.Gln27Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1267C>T p.Gln423Ter stop_gained De novo - - 30244534 Assoum M et al. (2018)
c.1331C>A p.Ser444Ter stop_gained De novo - - 30244534 Assoum M et al. (2018)
c.1338T>A p.Tyr446Ter stop_gained De novo - Simplex 30244534 Assoum M et al. (2018)
c.1375C>T p.Gln459Ter stop_gained De novo - Simplex 30244534 Assoum M et al. (2018)
c.445A>G p.Asn149Asp missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1105_1106delinsTA p.Gly369Ter stop_gained De novo - - 33508234 Weng PL et al. (2021)
c.1020del p.Ala342ArgfsTer16 frameshift_variant De novo - Simplex 30244534 Assoum M et al. (2018)
c.1100dup p.Cys367TrpfsTer43 frameshift_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.1067del p.Phe356SerfsTer2 frameshift_variant Unknown Not maternal - 33508234 Weng PL et al. (2021)
c.1461C>G p.Tyr487Ter stop_gained De novo - Multiplex (monozygotic twins) 33508234 Weng PL et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

Score Delta: Score remained at 3S

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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

7/1/2023
icon
3S

Increased from to 3S

Krishnan Probability Score

Score 0.4481915807793

Ranking 11711/25841 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 0.99201234063852

Ranking 1709/18225 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 0.93928381636668

Ranking 14156/18665 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 0.11812705761154

Ranking 5758/20870 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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