Human Gene Module / Chromosome 3 / TBC1D5

TBC1D5TBC1 domain family, member 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 10
Rare Variants / Common Variants
6 / 1
Aliases
-
Associated Syndromes
-
Chromosome Band
3p24.3
Associated Disorders
-
Relevance to Autism

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010).

Molecular Function

The encoded protein may act as a GTPase-activating protein for Rab family protein(s).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TBC1D5 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160 Zeigerer A , et al. (2004) No -
2 Highly Cited AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits Treebak JT , et al. (2006) No -
3 Recent Recommendation Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1 Kuijl C , et al. (2007) No -
4 Recent Recommendation The Rab GTPase-activating protein AS160 as a common regulator of insulin- and Galphaq-mediated intracellular GLUT4 vesicle distribution Yuasa T , et al. (2009) No -
5 Recent Recommendation AS160 modulates aldosterone-stimulated epithelial sodium channel forward trafficking Liang X , et al. (2010) No -
6 Primary Functional impact of global rare copy number variation in autism spectrum disorders Pinto D , et al. (2010) Yes -
7 Positive Association Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection Pardias AF , et al. (2018) No -
8 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Maternal Unknown 20531469 Pinto D , et al. (2010)
- - copy_number_loss Familial Paternal Unknown 20531469 Pinto D , et al. (2010)
c.788C>T p.Pro263Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1664C>T p.Ser555Phe missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2092C>T p.Gln698Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1138+1G>C - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
A>AT - intergenic_variant - - - 29483656 Pardias AF , et al. (2018)
SFARI Gene score
2

Strong Candidate

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010). These include three deletions involving exons. According to the UCSC browser, deletions have also been observed in controls, but not fully overlapping those reported by Pinto et al.

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

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010). These include three deletions involving exons. According to the UCSC browser, deletions have also been observed in controls, but not fully overlapping those reported by Pinto et al.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010). These include three deletions involving exons. According to the UCSC browser, deletions have also been observed in controls, but not fully overlapping those reported by Pinto et al.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010). These include three deletions involving exons. According to the UCSC browser, deletions have also been observed in controls, but not fully overlapping those reported by Pinto et al.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010). These include three deletions involving exons. According to the UCSC browser, deletions have also been observed in controls, but not fully overlapping those reported by Pinto et al.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare single-gene CNVs in the TBC1D5 gene were observed multiple times among 996 individuals of European ancestry with ASD but not in 1,287 matched controls (Pinto et al., 2010). These include three deletions involving exons. According to the UCSC browser, deletions have also been observed in controls, but not fully overlapping those reported by Pinto et al.

Krishnan Probability Score

Score 0.49118075492478

Ranking 5733/25841 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 6.5186439907099E-10

Ranking 16661/18225 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 0.94623893181713

Ranking 16790/18665 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 0.26247115751572

Ranking 3297/20870 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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