GPC1
protein-codingglypican 1, the group of Glypicans|MicroRNA protein coding host genes
Gene summary
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. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002081.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 2 | 6 | ||
| missense | 125 | 4 | 129 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 130 | 6 | 2 | 138 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002072.2 | 9 | MANE Select | |
| Ensembl | ENSP00000264039.2 | 9 | MANE Select | |
| Ensembl | ENSP00000415077.2 | 8 | Standard | |
| Ensembl | ENSP00000415077.2 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gpc1a | Danio rerio | Structure: extrahepatic duct Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
- VEGFA-VEGFR2 Signaling Pathway
- Developmental Biology
- Signaling by GPCR
Biological Process
- retinoid metabolic process
- glycosaminoglycan biosynthetic process
- glycosaminoglycan catabolic process
- axon guidance
- Schwann cell differentiation
Molecular Function
- copper ion binding
- fibroblast growth factor binding
- laminin binding
Cellular Component
- extracellular region
- extracellular space
- nucleoplasm
- endosome
- Golgi lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264039
- Coding exons
- 9
- Length
- 32406
- Individuals with no LoFs
- 125356
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125364
- p
- 0.0000319
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.333 | 346 | 364 | 0.951 | 0.0000257 | 3542 |
| Missense (PolyPhen) | 130 | 142.45 | 0.91262 | 1348 | ||
| Synonymous | -0.650 | 177 | 166 | 1.06 | 0.0000122 | 1154 |
| Loss of Function | 2.87 | 7 | 21.3 | 0.328 | 9.99e-7 | 238 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000073 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling. {ECO:0000250, ECO:0000269|PubMed:19936054, ECO:0000269|PubMed:21642435}.;
- Disease
- DISEASE: Note=Associates (via the heparan sulfate side chains) with fibrillar APP amyloid-beta peptides in primitive and classic amyloid plaques and may be involved in the deposition of these senile plaques in the Alzheimer disease (AD) brain (PubMed:15084524). {ECO:0000269|PubMed:15084524}.; DISEASE: Note=Misprocessing of GPC1 is found in fibroblasts of patients with Niemann-Pick Type C1 disease. This is due to the defective deaminative degradation of heparan sulfate chains (PubMed:16645004). {ECO:0000269|PubMed:16645004}.;
Recessive Scores
- pRec
- 0.262
Intolerance Scores
- LoFtool
- 0.358
- RVIS EVS
- -1.02
- RVIS percentile EVS
- 8.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.531