Human Gene Module / Chromosome 13 / GPC6

GPC6glypican 6

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 8
Rare Variants / Common Variants
4 / 6
Aliases
GPC6, OMIMD1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
13q31.3-q32.1
Associated Disorders
-
Relevance to Autism

Rare variants in the GPC6 gene have been identified with autism (Pinto et al., 2010). In particular, that study found two individuals with deletions and one individual with a duplication that involve GPC6.

Molecular Function

A member of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan family with a putative function of cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases.

Reports related to GPC6 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited GPC6, a novel member of the glypican gene family, encodes a product structurally related to GPC4 and is colocalized with GPC5 on human chromosome 13. Paine-Saunders S , et al. (1999) No -
2 Highly Cited Glypican-6, a new member of the glypican family of cell surface heparan sulfate proteoglycans. Veugelers M , et al. (1999) No -
3 Recent Recommendation Mutations in the heparan-sulfate proteoglycan glypican 6 (GPC6) impair endochondral ossification and cause recessive omodysplasia. Campos-Xavier AB , et al. (2009) No -
4 Recent Recommendation An interstitial duplication of chromosome 13q31.3q32.1 further delineates the critical region for postaxial polydactyly type A2. van der Zwaag PA , et al. (2009) No -
5 Primary Functional impact of global rare copy number variation in autism spectrum disorders. Pinto D , et al. (2010) Yes -
6 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder. Prasad A , et al. (2013) Yes -
7 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Girirajan S , et al. (2013) Yes -
8 Positive Association Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations. Liu X , et al. (2015) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 20531469 Pinto D , et al. (2010)
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss Unknown - Multiplex 23375656 Girirajan S , et al. (2013)
Common Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.161-110733G>T - intron_variant - - - 26314684 Liu X , et al. (2015)
c.161-111707G>A - intron_variant - - - 26314684 Liu X , et al. (2015)
c.161-116368A>G - intron_variant - - - 26314684 Liu X , et al. (2015)
c.161-146590C>T - intron_variant - - - 26314684 Liu X , et al. (2015)
c.161-117422G>A;c.161-117422G>C - intron_variant - - - 26314684 Liu X , et al. (2015)
c.161-88262G>A;c.-51+6255G>A;c.-51+1563G>A - intron_variant - - - 26314684 Liu X , et al. (2015)
SFARI Gene score
3

Suggestive Evidence

Rare variants in the GPC6 gene have been identified with autism (Pinto et al., 2010). In particular, that study found two individuals with deletions and one individual with a duplication that involve GPC6.

Score Delta: Score remained at 4

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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare variants in the GPC6 gene have been identified with autism (Pinto et al., 2010). In particular, that study found two individuals with deletions and one individual with a duplication that involve GPC6.

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

Increased from No data to 4

Description

Rare variants in the GPC6 gene have been identified with autism (Pinto et al., 2010). In particular, that study found two individuals with deletions and one individual with a duplication that involve GPC6.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variants in the GPC6 gene have been identified with autism (Pinto et al., 2010). In particular, that study found two individuals with deletions and one individual with a duplication that involve GPC6.

Krishnan Probability Score

Score 0.49263131272549

Ranking 4461/25841 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.
ExAC Score

Score 0.33885461335406

Ranking 6293/18225 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
Sanders TADA Score

Score 0.94959454657202

Ranking 18154/18665 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).
Zhang D Score

Score -0.24763768939153

Ranking 16337/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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