Human Gene Module / Chromosome 8 / TBC1D31

TBC1D31TBC1 domain family, member 31

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
7 / 0
Aliases
TBC1D31, Gm85,  WDR67
Associated Syndromes
-
Chromosome Band
8q24.13
Associated Disorders
-
Relevance to Autism

Two de novo missense variants in the TBC1D31 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P=7.29 x 10-3) (Iossifov et al., 2014; Krumm et al., 2015).

Molecular Function

This gene encodes a protein of unknown function.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TBC1D31 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
3 Support Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder Krupp DR , et al. (2017) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support - Woodbury-Smith M et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.444A>T p.Thr148%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.951T>A p.His317Gln missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.2364G>A p.Gln788= synonymous_variant De novo - Simplex 28867142 Krupp DR , et al. (2017)
c.2781C>G p.Asn927Lys missense_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
c.1931G>C p.Arg644Thr missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2493_2494del p.Met832ValfsTer3 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2183del p.Gln728ArgfsTer24 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants in the TBC1D31 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P-value 7.29 x 10-3) (Iossifov et al., 2014; Krumm et al., 2015).

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo missense variants in the TBC1D31 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P-value 7.29 x 10-3) (Iossifov et al., 2014; Krumm et al., 2015).

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Two de novo missense variants in the TBC1D31 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P-value 7.29 x 10-3) (Iossifov et al., 2014; Krumm et al., 2015).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2017
icon
3

Increased from to 3

Description

Two de novo missense variants in the TBC1D31 gene have been identified in ASD probands from the Simons Simplex Collection, with no de novo events in this gene observed in 1,786 unaffected siblings (P-value 7.29 x 10-3) (Iossifov et al., 2014; Krumm et al., 2015).

Reports Added
[Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.2017]
Krishnan Probability Score

Score 0.32888903319813

Ranking 25062/25841 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 1.3436459331833E-9

Ranking 16557/18225 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 0.94287253634282

Ranking 15471/18665 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
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