Human Gene Module / Chromosome 13 / GPC5

GPC5glypican 5

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
31 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
13q31.3
Associated Disorders
-
Relevance to Autism

De novo variants in the GPC gene have been identified in ASD probands, including de novo missense variants in probands from the Simons Simplex Collection and the Autism Sequencing Consortium (Kong et al., 2012; De Rubeis et al., 2014; Iossifov et al., 2014; Yuen et al., 216; Yuen et al., 2017; Turner et al., 2017). Functional assessment of the ASD-associated p.Met133Thr missense variant, which was originally identified in a proband from the Simons Simplex Collection, in Drosophila using an overexpression-based strategy in Macrogliese et al., 2022 demonstrated that flies overexpressing GPC5-p.Met133Thr exhibited increased lethality when compared with reference protein, indicating a gain-of-function effect.

Molecular Function

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GPC5 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Rate of de novo mutations and the importance of father's age to disease risk Kong A , et al. (2012) Yes -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
5 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
6 Support Genomic Patterns of De Novo Mutation in Simplex Autism Turner TN et al. (2017) Yes -
7 Recent Recommendation - Marcogliese PC et al. (2022) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Wang J et al. (2023) Yes -
Rare Variants   (31)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1561+3637C>T - intron_variant De novo - Simplex 22914163 Kong A , et al. (2012)
c.304C>T p.Arg102Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.1281-49306T>C - intron_variant De novo - Simplex 22914163 Kong A , et al. (2012)
c.1281-52725C>T - intron_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.1562-125313T>C - intron_variant De novo - Simplex 22914163 Kong A , et al. (2012)
c.1562-158138T>A - intron_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.1561+6983T>C - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.326-21446A>G - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.326-41070C>T - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1281-57674C>T - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1401+85263C>T - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1561+85485A>G - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.326-104875A>G - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1401+90476A>G - intron_variant De novo - Simplex 28965761 Turner TN et al. (2017)
c.163+7130T>A - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-266106T>C - intron_variant De novo - Simplex 28965761 Turner TN et al. (2017)
c.1280+8246C>G - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1154+13782A>G - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1561+47588T>A - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-49776A>G - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-67354A>C - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1561+129204T>C - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-136741T>C - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-186669T>A - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-336044A>C - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1562-353771C>T - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1292G>A p.Arg431His missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1352T>C p.Ile451Thr missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1513G>A p.Gly505Arg missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.398T>C p.Met133Thr missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.304C>A p.Arg102%3D synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
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.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.57265335745392

Ranking 702/25841 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 1.9911393973656E-5

Ranking 13887/18225 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 0.94542089763295

Ranking 16463/18665 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 -0.124490690121

Ranking 13293/20870 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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