Human Gene Module / Chromosome X / TBL1X

TBL1Xtransducin (beta)-like 1X-linked

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
0 / 3
Aliases
TBL1X, EBI,  SMAP55,  TBL1
Associated Syndromes
-
Chromosome Band
Xp22.31-p22.2
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the TBL1X gene and males with ASD in the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011).

Molecular Function

This is an F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. It plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TBL1X (1 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males Chung RH , et al. (2011) Yes -
Rare Variants  

No rare variants reported.

Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-43+2050G>A;c.-51+2050G>A - intron_variant - - - 22050706 Chung RH , et al. (2011)
c.-43+4699T>G;c.-51+4699T>G G/T intron_variant - - - 22050706 Chung RH , et al. (2011)
c.-43+6339G>A;c.-51+6339G>A C/T intron_variant - - - 22050706 Chung RH , et al. (2011)
SFARI Gene score
2

Strong Candidate

One SNP in the TBL1X gene showed chromosome-wide significance (but not genome-wide significance) in a large meta-analysis and joint analysis in males with ASD from the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). As well, rare deletions or mutations in the TBL1X gene have been previously reported in syndromic disorders that include autism, but CNVs overlapping this gene were also reported in controls (Thomas et al., 1999; Chocholska et al., 2006; Shinawi et al., 2009).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
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

One SNP in the TBL1X gene showed chromosome-wide significance (but not genome-wide significance) in a large meta-analysis and joint analysis in males with ASD from the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). As well, rare deletions or mutations in the TBL1X gene have been previously reported in syndromic disorders that include autism, but CNVs overlapping this gene were also reported in controls (Thomas et al., 1999; Chocholska et al., 2006; Shinawi et al., 2009).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

One SNP in the TBL1X gene showed chromosome-wide significance (but not genome-wide significance) in a large meta-analysis and joint analysis in males with ASD from the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). As well, rare deletions or mutations in the TBL1X gene have been previously reported in syndromic disorders that include autism, but CNVs overlapping this gene were also reported in controls (Thomas et al., 1999; Chocholska et al., 2006; Shinawi et al., 2009).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

One SNP in the TBL1X gene showed chromosome-wide significance (but not genome-wide significance) in a large meta-analysis and joint analysis in males with ASD from the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). As well, rare deletions or mutations in the TBL1X gene have been previously reported in syndromic disorders that include autism, but CNVs overlapping this gene were also reported in controls (Thomas et al., 1999; Chocholska et al., 2006; Shinawi et al., 2009).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

One SNP in the TBL1X gene showed chromosome-wide significance (but not genome-wide significance) in a large meta-analysis and joint analysis in males with ASD from the HIHG/CHGR, AGRE and ACC cohorts (Chung et al., 2011). As well, rare deletions or mutations in the TBL1X gene have been previously reported in syndromic disorders that include autism, but CNVs overlapping this gene were also reported in controls (Thomas et al., 1999; Chocholska et al., 2006; Shinawi et al., 2009).

Krishnan Probability Score

Score 0.49743032347299

Ranking 2388/25841 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 0.99850030278011

Ranking 1184/18225 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 0.93860398731133

Ranking 13920/18665 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
Larsen Cumulative Evidence Score

Score 3

Ranking 365/461 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.
Original Source
Zhang D Score

Score 0.13321863968038

Ranking 5495/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
HP "<span title=""The name recommended by the UniProt consortium for this chain/part."" class=""tooltipped RECOMMENDED""><a href=""#PRO_0000028457"" onclick=""uniprot.entryViews.openSectionForInternalLink('PRO_0000028457');"">Haptoglobin alpha chain</a>" Human Protein Binding 3240 P00738
MKX Homeobox protein Mohawk Human Protein Binding 283078 Q8IYA7
WDR59 WD repeat-containing protein 59 Human Protein Binding 79726 Q6PJI9
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