Human Gene Module / Chromosome 15 / TUBGCP5

TUBGCP5tubulin, gamma complex associated protein 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
8 / 0
Aliases
TUBGCP5, GCP5
Associated Syndromes
-
Chromosome Band
15q11.2
Associated Disorders
ID
Relevance to Autism

A rare mutation in the TUBGCP5 gene has been identified in an individual with ASD (Sanders et al., 2012). In addition, a rare TUBGCP5 deletion was found in a patient with PDD-NOS and mild intellectual disability (Leblond et al., 2012).

Molecular Function

The Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TUBGCP5 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder van der Zwaag B , et al. (2009) Yes -
2 Primary Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders Leblond CS , et al. (2012) Yes ID
3 Support De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) Yes -
4 Support Neurogenetic analysis of childhood disintegrative disorder Gupta AR , et al. (2017) No -
5 Support - Woodbury-Smith M et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.270A>G p.Glu90%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.200+5G>C - splice_site_variant De novo - Simplex 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Paternal Simplex 22346768 Leblond CS , et al. (2012)
c.102C>T p.Asp34%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1828G>A p.Asp610Asn missense_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
c.3044T>C p.Leu1015Ser missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
- - copy_number_gain Familial Paternal Multi-generational 20029941 van der Zwaag B , et al. (2009)
c.820A>T p.Thr274Ser missense_variant Familial Maternal Multiplex (monozygotic twins) 28392909 Gupta AR , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

TUBGCP5 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012). A novel de novo possibly damaging missense variant in TUBGCP5 was observed in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012.

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

TUBGCP5 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012). A novel de novo possibly damaging missense variant in TUBGCP5 was observed in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

TUBGCP5 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012). A novel de novo possibly damaging missense variant in TUBGCP5 was observed in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012.

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

TUBGCP5 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012). A novel de novo possibly damaging missense variant in TUBGCP5 was observed in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012.

Krishnan Probability Score

Score 0.40475467910124

Ranking 23215/25841 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 0.0001261971671947

Ranking 12965/18225 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 0.93747130591936

Ranking 13536/18665 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 5

Ranking 295/461 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 0.18299284298496

Ranking 4546/20870 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
CNVs associated with TUBGCP5(1 CNVs)
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15q11.2 122 Deletion-Duplication 161  /  2259
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