GPC1

glypican 1, the group of Glypicans|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:240435663-240468076

Links

ENSG00000063660 ∙ NCBI:2817 ∙ OMIM:600395 ∙ HGNC:4449 ∙ Uniprot:P35052 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			46	4		50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	46	5	2

Variants in GPC1

This is a list of pathogenic ClinVar variants found in the GPC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-240435928-C-T		not specified	Uncertain significance (May 18, 2022)
2-240435937-G-A		not specified	Uncertain significance (May 30, 2023)
2-240435955-G-A		not specified	Uncertain significance (Feb 16, 2023)
2-240436006-C-G		not specified	Uncertain significance (Nov 23, 2024)
2-240436021-G-A		not specified	Uncertain significance (Aug 27, 2024)
2-240436051-A-G		not specified	Uncertain significance (Jul 19, 2023)
2-240459101-C-T		not specified	Uncertain significance (Dec 03, 2021)
2-240459125-G-A		not specified	Uncertain significance (Dec 18, 2023)
2-240459146-G-A		not specified	Uncertain significance (Feb 15, 2023)
2-240459161-C-T		not specified	Uncertain significance (Sep 17, 2021)
2-240462202-C-T		not specified	Uncertain significance (May 06, 2024)
2-240462227-C-T		not specified	Uncertain significance (Aug 27, 2024)
2-240462243-C-G		not specified	Uncertain significance (Nov 24, 2024)
2-240462244-C-T		not specified	Uncertain significance (Apr 17, 2024)
2-240462246-C-T			Benign (Dec 31, 2019)
2-240462290-G-A		not specified	Uncertain significance (Apr 07, 2022)
2-240462292-G-A		not specified	Uncertain significance (Feb 07, 2023)
2-240462292-G-T		not specified	Uncertain significance (Sep 27, 2024)
2-240462310-C-T		not specified	Uncertain significance (Jul 05, 2023)
2-240462311-G-A			Likely benign (Apr 03, 2018)
2-240462383-G-A		not specified	Uncertain significance (Aug 02, 2022)
2-240462437-G-A		not specified	Uncertain significance (Jun 07, 2024)
2-240462473-G-C		not specified	Uncertain significance (Nov 24, 2024)
2-240462479-C-T		not specified	Uncertain significance (Jul 14, 2021)
2-240462493-C-T		not specified	Uncertain significance (Jun 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPC1	protein_coding	protein_coding	ENST00000264039	9	32406

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0155	0.983	125356	0	8	125364	0.0000319

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.333	346	364	0.951	0.0000257	3542
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000102	0.0000912
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000884
Middle Eastern	0.00	0.00
South Asian	0.000168	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Fluid shear stress and atherosclerosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);VEGFA-VEGFR2 Signaling Pathway;Developmental Biology;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism of carbohydrates;A tetrasaccharide linker sequence is required for GAG synthesis;HS-GAG biosynthesis;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Metabolism;Metabolism of vitamins and cofactors;Integrin;Cell surface interactions at the vascular wall;Hemostasis;Retinoid metabolism and transport;Signaling by ROBO receptors;G alpha (i) signalling events;Axon guidance;Visual phototransduction;GPCR downstream signalling;Wnt Canonical;Glypican 1 network;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.262

Intolerance Scores

• loftool: 0.358
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.14

Haploinsufficiency Scores

• pHI: 0.184
• hipred: Y
• hipred_score: 0.824
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.531

Mouse Genome Informatics

• Gene name: Gpc1
• Phenotype: homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); neoplasm

Zebrafish Information Network

• Gene name: gpc1a
• Affected structure: extrahepatic duct
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: retinoid metabolic process;glycosaminoglycan biosynthetic process;glycosaminoglycan catabolic process;axon guidance;Schwann cell differentiation;heparan sulfate proteoglycan catabolic process;myelin assembly;negative regulation of fibroblast growth factor receptor signaling pathway;leukocyte migration;positive regulation of skeletal muscle cell differentiation
• Cellular component: extracellular region;extracellular space;nucleoplasm;endosome;Golgi lumen;cytosol;plasma membrane;extracellular matrix;intrinsic component of plasma membrane;lysosomal lumen;membrane raft;synapse;anchored component of plasma membrane;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: copper ion binding;fibroblast growth factor binding;laminin binding