GPC1

Summary

GPC1 (glypican 1, HGNC:4449) is a protein-coding gene on chromosome 2q37.3, encoding Glypican-1 (P35052). Cell surface proteoglycan that bears heparan sulfate.

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.

Source: NCBI Gene 2817 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 145 total — 1 pathogenic
• MANE Select transcript: NM_002081

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4449
Approved symbol	GPC1
Name	glypican 1
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	glypican
Ensembl gene	ENSG00000063660
Ensembl biotype	protein_coding
OMIM	600395
Entrez	2817

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264039, ENST00000420138, ENST00000425056, ENST00000426280, ENST00000427506, ENST00000455111, ENST00000466624, ENST00000469694, ENST00000495100, ENST00000897332, ENST00000897333, ENST00000943307, ENST00000943308

RefSeq mRNA: 1 — MANE Select: NM_002081 NM_002081

CCDS: CCDS2534

Canonical transcript exons

ENST00000264039 — 9 exons

Exon	Start	End
ENSE00001259901	240466058	240468076
ENSE00001259907	240435663	240436084
ENSE00001259922	240464616	240464746
ENSE00001259944	240463347	240463512
ENSE00003492854	240459030	240459188
ENSE00003495334	240465473	240465648
ENSE00003542120	240465077	240465210
ENSE00003602748	240464856	240464975
ENSE00003607727	240462191	240462582

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.6129 / max 438.4567, expressed in 1491 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26394	30.0054	1460
26401	3.3094	600
26398	2.0600	1014
26397	1.8720	1013
26396	1.4018	857
26399	1.1933	757
26400	0.5948	326
26402	0.5124	190
26395	0.3715	234
26405	0.1294	29

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.40	gold quality
apex of heart	UBERON:0002098	98.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.65	gold quality
skin of abdomen	UBERON:0001416	97.60	gold quality
stromal cell of endometrium	CL:0002255	97.53	gold quality
right frontal lobe	UBERON:0002810	97.51	gold quality
lower esophagus mucosa	UBERON:0035834	97.51	gold quality
tibial nerve	UBERON:0001323	97.24	gold quality
skin of leg	UBERON:0001511	97.19	gold quality
heart left ventricle	UBERON:0002084	97.08	gold quality
cerebellar hemisphere	UBERON:0002245	96.97	gold quality
cardiac ventricle	UBERON:0002082	96.90	gold quality
cerebellar cortex	UBERON:0002129	96.90	gold quality
periodontal ligament	UBERON:0008266	96.86	gold quality
tibia	UBERON:0000979	96.63	gold quality
gastrocnemius	UBERON:0001388	96.55	gold quality
ganglionic eminence	UBERON:0004023	96.48	gold quality
sural nerve	UBERON:0015488	96.25	gold quality
left adrenal gland cortex	UBERON:0035825	96.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.13	gold quality
esophagus mucosa	UBERON:0002469	96.11	gold quality
left adrenal gland	UBERON:0001234	96.10	gold quality
right adrenal gland cortex	UBERON:0035827	96.02	gold quality
right adrenal gland	UBERON:0001233	95.91	gold quality
descending thoracic aorta	UBERON:0002345	95.87	gold quality
zone of skin	UBERON:0000014	95.75	gold quality
right atrium auricular region	UBERON:0006631	95.55	gold quality
muscle of leg	UBERON:0001383	95.54	gold quality
adenohypophysis	UBERON:0002196	95.31	gold quality
cerebellum	UBERON:0002037	95.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	74.75
E-ANND-3	yes	9.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FGF2, RUNX2

miRNA regulators (miRDB)

74 targeting GPC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-3P	99.47	65.24	1811

Literature-anchored findings (GeneRIF, showing 40)

• Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. (PMID:11968010)
• S-nitrosylation and Copper-dependent autocleavage of glypican 1 (PMID:12084716)
• inhibition of Gpc-1 expression abrogates spermine uptake and intracellular delivery; ascorbate released NO, which degraded heparan sulfate side chains and liberated the bound spermine (PMID:12972423)
• glypican-1 is required for efficient TGF-beta1 signaling in pancreatic cancer cells (PMID:15249209)
• syndecan-1 and glypican-1 have roles in progression of ovarian cancer (PMID:15297422)
• glypican 1 (GPC1) is deleted in both reported patients suffering from Albright hereditary osteodystrophy-like (AHO-like) syndrome (PMID:15547662)
• altered HSPGs contribute to enhanced signaling of FGF-2 via FGFR1c in gliomas with glypican-1 playing a significant role in this mitogenic pathway (PMID:16723715)
• Enhanced GPC1 expression correlates with BMP and activin receptors in pancreatic cancer. (PMID:17016645)
• cancer cell- and host-derived GPC1 are crucial for full mitogenic, angiogenic, and metastatic potential of cancer cells (PMID:18064304)
• Glypican-3 can be especially useful in the identification of poorly differentiated hepatocellular carcinoma. (PMID:18536657)
• study concludes that Abeta can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these heparan sulfate proteoglycans in Alzheimer’s disease lesions (PMID:19166823)
• The N-unsubstituted glucosamine residues are formed during biosynthesis of glypican-1 and the content increased upon inhibition of polyamine synthesis. (PMID:19479373)
• High glucose can decrease the expression of core protein Sydecan-1 and Glypican-1 in cultured human renal glomerular endothelial cells. (PMID:21265098)
• Mutagenesis and enzymatic cleavage indicated that the potential N-glycosylation sites are invariably occupied. (PMID:21932778)
• Crystal structure of N-glycosylated human glypican-1 core protein shows the structure of two loops evolutionarily conserved in vertebrate glypican-1 (PMID:22351761)
• We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media (PMID:23624389)
• DNA from 4 HPV positive and 4 HPV negative fresh frozen primary HNSCC were subject to comprehensive genome-wide methylation profiling.Pathway analysis of 1168 methylated genes showed 8 signal transduction pathways (GPC1) of which 62% are hypermethylated. (PMID:23736812)
• GPC1 and FGFR1 are targets for regulation of their gene expression by miR-149. (PMID:24463821)
• differences in expression among different subtypes of ameloblastomas (PMID:25046223)
• GPC1(+) crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease in patients with early-and late-stage pancreatic cancer. (PMID:26106858)
• The C terminus is shown to be highly flexible in solution, but it orients the core protein transverse to the membrane, directing a surface evolutionarily conserved in Gpc1 orthologs toward the membrane, where it may interact with signaling molecules (PMID:26203194)
• Data show that notum and glypican-1 and glypican-3 gene expression during colorectal cancer (CRC) development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis. (PMID:26517809)
• independent case-control study implicated that common SNPs in GPC1 gene contributed to biliary atresia susceptibility in Chinese population (PMID:27373597)
• Glypican-1 was validated as a novel substrate for ADAM17, with important function in adhesion, proliferation and migration of carcinoma cells. (PMID:27576135)
• The role of glypican-1 in mediating the eNOS activation under shear stress might involve in protecting the endothelial function against disturbed flow. (PMID:27688027)
• Exosomal miR signature is superior to exosomal GPC1 or plasma CA 19-9 levels in establishing a diagnosis of pancreatic ductal carcinoma and differentiating between PDAC and chronic pancreatitis. (PMID:28232049)
• The results demonstrated that the GPC1 gene was re-expressed in pancreatic ductal adenocarcinoma (PDAC) mainly due to promoter hypomethylation, even for early-stage PDAC. High levels of GPC1 were associated with poorer pathological differentiation and worse biological behaviors. GPC1 could serve as an independent unfavorable prognostic factor in PDAC. (PMID:28440066)
• High GPC1 expression is associated with uterine cervical cancer. (PMID:29055044)
• This protein may play a role in the control of cell division and growth regulation. It may be a positive marker of epithelioid mesothelioma. (PMID:29327712)
• glypican-1 IHC does not differentiate mesothelioma from pulmonary adenocarcinoma. (PMID:29785020)
• Results indicate that high levels of serum GPC1 predict poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients. Serum GPC1 may be a prognosis factor for PDAC patients. (PMID:30358133)
• Glypican-1 promotes the aggressive proliferation of esophageal squamous carcinoma cells by regulating the PTEN/Akt/beta-catenin signaling pathway. (PMID:30730015)
• expression significantly reduced in first-trimester small for gestational age as well as in the third-trimester fetal growth restriction placentae compared to controls (PMID:30803713)
• Clinical significance of glypican-3-positive circulating tumor cells of hepatocellular carcinoma patients. (PMID:31141571)
• Highly (SN12L1) and low (SN12C) metastatic renal carcinoma cell line were analyzed. There was significant elevation of Glypican-1 protein expression in the SN12L1 cells relative to the SN12C cells while there were no significant differences in Syndecan-1 or CD44. Knock down of Glypican-1 by siRNA completely blocked flow induced migration in SN12L1 cells. MAPK inhibitors also blocked flow induced migration in SN12L1 cells. (PMID:31256115)
• Paradoxical Role of Glypican-1 in Prostate Cancer Cell and Tumor Growth. (PMID:31391540)
• Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer. (PMID:32152502)
• Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility. (PMID:32315284)
• The glycocalyx core protein Glypican 1 protects vessel wall endothelial cells from stiffness-mediated dysfunction and disease. (PMID:32647868)
• Structure, Dynamics, and Interactions of GPI-Anchored Human Glypican-1 with Heparan Sulfates in a Membrane. (PMID:33021626)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpc1a	ENSDARG00000019341
danio_rerio	gpc1b	ENSDARG00000090585
mus_musculus	Gpc1	ENSMUSG00000034220
rattus_norvegicus	Gpc1	ENSRNOG00000049437
drosophila_melanogaster	dlp	FBGN0041604

Paralogs (5): GPC4 (ENSG00000076716), GPC3 (ENSG00000147257), GPC5 (ENSG00000179399), GPC6 (ENSG00000183098), GPC2 (ENSG00000213420)

Protein

Protein identifiers

Glypican-1 — P35052 (reviewed: P35052)

All UniProt accessions (7): P35052, A0A384NPH9, C9J4Y6, H7BZE9, H7BZL4, H7C024, H7C410

UniProt curated annotations — full annotation on UniProt →

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. 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.

Subcellular location. Cell membrane. Endosome Secreted. Extracellular space.

Post-translational modifications. S-nitrosylated in a Cu(2+)-dependent manner. Nitric acid (NO) is released from the nitrosylated cysteines by ascorbate or by some other reducing agent, in a Cu(2+) or Zn(2+) dependent manner. This free nitric oxide is then capable of cleaving the heparan sulfate side chains. N- and O-glycosylated. N-glycosylation is mainly of the complex type containing sialic acid. O-glycosylated with heparan sulfate. The heparan sulfate chains can be cleaved either by the action of heparanase or, degraded by a deaminative process that uses nitric oxide (NO) released from the S-nitrosylated cysteines. This process is triggered by ascorbate, or by some other reducing agent, in a Cu(2+)- or Zn(2+) dependent manner. Cu(2+) ions are provided by ceruloproteins such as APP, PRNP or CP which associate with GCP1 in intracellular compartments or lipid rafts. This cell-associated glypican is further processed to give rise to a medium-released species.

Disease relevance. 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. 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.

Similarity. Belongs to the glypican family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35052-1	1	yes
P35052-2	2

RefSeq proteins (1): NP_002072* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001863	Glypican	Family
IPR019803	Glypican_CS	Conserved_site

Pfam: PF01153

UniProt features (59 total): helix 23, disulfide bond 7, strand 7, glycosylation site 5, splice variant 3, chain 2, sequence variant 2, mutagenesis site 2, turn 2, region of interest 2, signal peptide 1, propeptide 1, compositionally biased region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4YWT	X-RAY DIFFRACTION	2.38
4BWE	X-RAY DIFFRACTION	2.46
4ACR	X-RAY DIFFRACTION	2.55
4AD7	X-RAY DIFFRACTION	2.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35052-F1	83.14	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 530

Disulfide bonds (7): 32–68, 62–256, 69–259, 191–343, 246–279, 268–415, 272–401

Glycosylation sites (5): 486, 488, 490, 79, 116

Mutagenesis-validated functional residues (2):

Position	Phenotype
79	protein yield reduced by half. protein yield reduced by 90%, abolishes n-glycosylation but no effect on secondary struct
116	no effect on protein yield. protein yield reduced by 90%, abolishes n-glycosylation but no effect on secondary structure

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-376176	Signaling by ROBO receptors
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 273 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOLDRATH_IMMUNE_MEMORY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, HEIDENBLAD_AMPLICON_8Q24_DN, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, BRUECKNER_TARGETS_OF_MIRLET7A3_DN

GO Biological Process (8): Schwann cell differentiation (GO:0014037), cell migration (GO:0016477), heparan sulfate proteoglycan catabolic process (GO:0030200), myelin assembly (GO:0032288), negative regulation of fibroblast growth factor receptor signaling pathway (GO:0040037), regulation of protein localization to membrane (GO:1905475), positive regulation of skeletal muscle cell differentiation (GO:2001016), regulation of signal transduction (GO:0009966)

GO Molecular Function (4): copper ion binding (GO:0005507), fibroblast growth factor binding (GO:0017134), laminin binding (GO:0043236), protein binding (GO:0005515)

GO Cellular Component (16): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), endosome (GO:0005768), Golgi lumen (GO:0005796), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular matrix (GO:0031012), lysosomal lumen (GO:0043202), membrane raft (GO:0045121), synapse (GO:0045202), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Dengue Virus Infection	2
Glycosaminoglycan metabolism	1
Hemostasis	1
Axon guidance	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
membrane	2
peripheral nervous system development	1
glial cell differentiation	1
cell motility	1
proteoglycan catabolic process	1
heparan sulfate proteoglycan metabolic process	1
cellular component assembly involved in morphogenesis	1
myelination	1
fibroblast growth factor receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of fibroblast growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
regulation of protein localization	1
regulation of cellular localization	1
protein localization to membrane	1
skeletal muscle cell differentiation	1
positive regulation of cell differentiation	1
regulation of skeletal muscle cell differentiation	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
transition metal ion binding	1
growth factor binding	1
protein binding	1
extracellular matrix binding	1
binding	1
nuclear lumen	1
endomembrane system	1
cytoplasmic vesicle	1
Golgi apparatus	1
intracellular organelle lumen	1
cytoplasm	1
cell periphery	1
external encapsulating structure	1
lysosome	1
vacuolar lumen	1
membrane microdomain	1
cell junction	1

Protein interactions and networks

STRING

2086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPC1	COL18A1	P39060	965
GPC1	SDC1	P18827	962
GPC1	SLIT3	O75094	890
GPC1	FGF2	P09038	875
GPC1	SDC2	P34741	875
GPC1	FGF17	O60258	834
GPC1	CD44	P16070	832
GPC1	EPCAM	P16422	822
GPC1	HSPG2	P98160	820
GPC1	PTPRS	Q13332	812
GPC1	EGFR	P00533	778
GPC1	FGF16	O43320	773
GPC1	FGF9	P31371	773
GPC1	SDC4	P31431	773
GPC1	NOTUM	Q6P988	773

IntAct

94 interactions, top by confidence:

A	B	Type	Score
GPC1	HADHB	psi-mi:“MI:0914”(association)	0.740
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
HADHB	POTEI	psi-mi:“MI:0914”(association)	0.530
FGF1	SDC4	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
CAVIN1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
HADHA	GPC4	psi-mi:“MI:0914”(association)	0.530
GPR183	GPC1	psi-mi:“MI:0914”(association)	0.530
LRRTM4	SGPL1	psi-mi:“MI:0914”(association)	0.530
GPC1	SEC11A	psi-mi:“MI:0914”(association)	0.530
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
Gpr158	GPC1	psi-mi:“MI:0915”(physical association)	0.500
FAM20B	GPC1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
APP	GPC1	psi-mi:“MI:0407”(direct interaction)	0.440
EXT1	GPC1	psi-mi:“MI:0559”(glycosylation reaction)	0.440

BioGRID (206): GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), GPC1 (Reconstituted Complex), GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), USP3 (Affinity Capture-MS), FANCE (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), TMEM245 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS)

ESM2 similar proteins: A2BDP1, A4IFM1, A4IHZ3, A5A6P7, B1AL88, F1QCC6, G3X745, L7VG99, O14525, O75487, O75949, O93279, P05067, P12023, P13265, P15943, P35052, P35053, P50593, P51653, P51654, P51655, P53601, P78333, P79307, P86009, Q06335, Q06481, Q0V9W0, Q14DG7, Q24114, Q32LT7, Q568B8, Q5EGE1, Q5IS80, Q5RE54, Q60495, Q61137, Q6P1U2, Q6V9Y8

Diamond homologs: F1QCC6, G3X745, O75487, P35052, P35053, P50593, P51653, P51655, Q0V9W0, Q5RE54, Q8BKV1, Q8N158, Q9QZF2, Q9R087, Q9Y625

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLIT1	up-regulates	GPC1	binding
SLIT2	up-regulates	GPC1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Glycosaminoglycan-protein linkage region biosynthesis	5	27.4×	2e-04
Regulation of clotting cascade	6	19.4×	2e-04
Protein-protein interactions at synapses	5	18.4×	6e-04
Neurexins and neuroligins	5	13.7×	2e-03
PIP3 activates AKT signaling	7	6.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

145 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	122
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1711534	GRCh37/hg19 2q37.3(chr2:239229304-243199373)x1	Pathogenic

SpliceAI

1945 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240436083:GG:G	donor_gain	1.0000
2:240436084:GG:G	donor_gain	1.0000
2:240436085:G:GG	donor_gain	1.0000
2:240436085:GTG:G	donor_loss	1.0000
2:240436086:T:A	donor_loss	1.0000
2:240459025:CACAG:C	acceptor_loss	1.0000
2:240459027:CA:C	acceptor_loss	1.0000
2:240459028:A:T	acceptor_loss	1.0000
2:240459029:G:GC	acceptor_loss	1.0000
2:240459029:GGT:G	acceptor_gain	1.0000
2:240459029:GGTGA:G	acceptor_gain	1.0000
2:240459185:GATG:G	donor_gain	1.0000
2:240459186:ATG:A	donor_gain	1.0000
2:240459186:ATGG:A	donor_loss	1.0000
2:240459187:TG:T	donor_gain	1.0000
2:240459188:GG:G	donor_gain	1.0000
2:240459189:G:GG	donor_gain	1.0000
2:240459190:T:A	donor_loss	1.0000
2:240462571:A:T	donor_gain	1.0000
2:240462580:CAGG:C	donor_loss	1.0000
2:240462581:AGGTG:A	donor_loss	1.0000
2:240462583:G:GC	donor_loss	1.0000
2:240462584:T:A	donor_loss	1.0000
2:240464602:AAC:A	acceptor_gain	1.0000
2:240464604:C:CA	acceptor_gain	1.0000
2:240464729:G:T	donor_gain	1.0000
2:240464744:AAG:A	donor_loss	1.0000
2:240464745:AGGT:A	donor_loss	1.0000
2:240464746:GGTGC:G	donor_loss	1.0000
2:240464747:GT:G	donor_loss	1.0000

AlphaMissense

3620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240465521:C:A	N439K	0.999
2:240465521:C:G	N439K	0.999
2:240465190:G:C	W416C	0.998
2:240465190:G:T	W416C	0.998
2:240459047:T:A	C62S	0.997
2:240459047:T:C	C62R	0.997
2:240459048:G:A	C62Y	0.997
2:240459048:G:C	C62S	0.997
2:240459068:T:A	C69S	0.997
2:240459069:G:C	C69S	0.997
2:240463396:G:A	C256Y	0.997
2:240463397:T:G	C256W	0.997
2:240465583:T:C	L460P	0.997
2:240463404:T:A	C259S	0.996
2:240463405:G:C	C259S	0.996
2:240463451:T:A	N274K	0.996
2:240463451:T:G	N274K	0.996
2:240463464:T:C	C279R	0.996
2:240463497:T:A	W290R	0.996
2:240463497:T:C	W290R	0.996
2:240459049:T:G	C62W	0.995
2:240459068:T:C	C69R	0.995
2:240459069:G:A	C69Y	0.995
2:240459070:C:G	C69W	0.995
2:240463395:T:A	C256S	0.995
2:240463396:G:C	C256S	0.995
2:240463461:G:C	G278R	0.995
2:240463499:G:C	W290C	0.995
2:240463499:G:T	W290C	0.995
2:240464868:T:A	C343S	0.995

dbSNP variants (sampled 300 via entrez): RS1000087580 (2:240457918 T>C), RS1000129114 (2:240438139 T>C), RS1000205312 (2:240455237 C>T), RS1000283780 (2:240442527 C>A), RS1000524489 (2:240441685 T>G), RS1000555968 (2:240455110 A>G), RS1000567761 (2:240441703 T>A,C,G), RS1000576671 (2:240441930 G>T), RS1000693090 (2:240436830 G>T), RS1000699050 (2:240465761 C>T), RS1000729798 (2:240465554 C>G), RS1000734328 (2:240436997 C>G), RS1000735426 (2:240445907 G>A), RS1000892946 (2:240461916 C>G,T), RS1000941104 (2:240454536 G>A)

Disease associations

OMIM: gene MIM:600395 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000271_6	Brain imaging in schizophrenia (dorsolateral prefrontal cortex interaction)	4.000000e-06
GCST012331_1	BMI x SSRI levels interaction in schizophrenia or bipolar disorder	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005658	response to selective serotonin reuptake inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	6
sodium arsenite	affects cotreatment, increases abundance, increases expression	4
Smoke	increases abundance, increases expression	3
Aflatoxin B1	increases methylation, increases expression	3
Acetaminophen	increases expression	2
Cadmium	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Lead	affects expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	increases expression	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sulforaphane	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
ochratoxin A	increases acetylation, increases expression	1
cupric chloride	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
bicalutamide	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
monomethylarsonous acid	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8GY	Abcam HCT 116 GPC1 KO	Cancer cell line	Male
CVCL_B9J7	Abcam A-549 GPC1 KO	Cancer cell line	Male
CVCL_D7QU	Ubigene A-549 GPC1 KO	Cancer cell line	Male
CVCL_D8F1	Ubigene BxPC-3 GPC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.