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GPC3 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- GPC3 (HGNC:4451) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- glypican 3
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- SDYS
- Alias symbols
- OCI-5, SGBS, SGBS1, SGB, DGSX
- %HI
- 1.17(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.16(Read more about gnomAD LOEUF score)
- Cytoband
- Xq26.2
- Genomic Coordinates
-
GRCh37/hg19: chrX:132669773-133119621 NCBI Ensembl UCSC GRCh38/hg38: chrX:133535745-133985594 NCBI Ensembl UCSC - MANE Select Transcript
- NM_004484.4 ENST00000370818.8 (Read more about MANE Select)
- Function
- Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI- anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (By similarity). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (By similarity). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stim... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- Simpson-Golabi-Behmel syndrome type 1 Monarch
-
PUBMED:
30447178
Vuillaume et al. (2018) reviewed 57 previously described GPC3 variants identified in 71 unrelated families. In addition they identified and additional 38 GPC3 variants in tn a patient cohort of 49 unrelated families. Variant types included large deletions (34.9%) followed by frameshift mutations leading to a stop premature codon (24.4%), nonsense (16.3%), missense (8.1%), large intragenic duplications (8.1%), splice site mutations (4.7%), translocations (2.3%), and one in frame mutation (1.2%).
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PUBMED:
21362501
Weichert et al. (2011) reported the prenatal findings of a fetus with a 1 MB deletion that includes the entire GPC3 gene, arr Xq26.2(132191191_133257323)x0; NCBI Build 36.1) and encompassing GPC4, GPC3 and CCDC160 . The most commonly found antenatal features of postnatally confirmed cases of SGBS1 included craniofacial anomalies, marked macrosomia, increased nuchal translucency and polyhydramnios.
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PUBMED:
10814714
Veuglelers et al. (2000) identified 6 SBGS1 patients with variants predicted to result in loss of function (1 frameshift, 3 nonsense, 1 splice site, 1 intragenic deletion . Expression analysis studies of one missense variant W296R that changes a highly conserved amnio acid resulted in a poorly processed protein and failed to increase the cell surface expression of heparan sulfate, suggesting that this missense mutation is also a loss-of-function mutation.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
