GPC2

Summary

GPC2 (glypican 2, HGNC:4450) is a protein-coding gene on chromosome 7q22.1, encoding Glypican-2 (Q8N158). Cell surface proteoglycan that bears heparan sulfate.

Predicted to be involved in several processes, including positive regulation of neuron projection development; regulation of protein localization to membrane; and smoothened signaling pathway. Located in endoplasmic reticulum.

Source: NCBI Gene 221914 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 96 total — 1 likely-pathogenic
• MANE Select transcript: NM_152742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4450
Approved symbol	GPC2
Name	glypican 2
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	cerebroglycan, FLJ38962, DKFZp547M109
Ensembl gene	ENSG00000213420
Ensembl biotype	protein_coding
OMIM	618446
Entrez	221914

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000292377, ENST00000471717, ENST00000480087, ENST00000486702, ENST00000490629, ENST00000893618, ENST00000919185

RefSeq mRNA: 1 — MANE Select: NM_152742 NM_152742

CCDS: CCDS5689

Canonical transcript exons

ENST00000292377 — 10 exons

Exon	Start	End
ENSE00001181053	100169606	100170483
ENSE00001181055	100177034	100177381
ENSE00003472417	100175572	100175894
ENSE00003488203	100171539	100171678
ENSE00003498178	100172087	100172217
ENSE00003553671	100174685	100174765
ENSE00003563118	100173835	100173997
ENSE00003620268	100176207	100176365
ENSE00003669867	100171261	100171436
ENSE00003694387	100171779	100171925

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1635 / max 182.7355, expressed in 1186 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85174	8.1635	1186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.78	gold quality
cortical plate	UBERON:0005343	95.44	gold quality
left ventricle myocardium	UBERON:0006566	89.58	gold quality
kidney epithelium	UBERON:0004819	89.23	gold quality
upper arm skin	UBERON:0004263	89.08	silver quality
cardiac muscle of right atrium	UBERON:0003379	88.62	gold quality
vena cava	UBERON:0004087	87.90	silver quality
nasal cavity epithelium	UBERON:0005384	86.65	gold quality
ventricular zone	UBERON:0003053	86.30	gold quality
cerebellar vermis	UBERON:0004720	85.88	silver quality
sperm	CL:0000019	85.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.16	gold quality
tendon of biceps brachii	UBERON:0008188	84.03	silver quality
pericardium	UBERON:0002407	83.22	silver quality
epithelial cell of pancreas	CL:0000083	83.04	gold quality
thymus	UBERON:0002370	82.69	gold quality
buccal mucosa cell	CL:0002336	82.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.74	gold quality
pons	UBERON:0000988	80.42	gold quality
cardia of stomach	UBERON:0001162	80.23	gold quality
left testis	UBERON:0004533	79.96	gold quality
vastus lateralis	UBERON:0001379	79.83	gold quality
skin of abdomen	UBERON:0001416	79.72	gold quality
ventral tegmental area	UBERON:0002691	79.68	silver quality
nipple	UBERON:0002030	79.66	silver quality
globus pallidus	UBERON:0001875	79.38	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.31	gold quality
right testis	UBERON:0004534	79.18	gold quality
medial globus pallidus	UBERON:0002477	79.07	gold quality
testis	UBERON:0000473	79.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	15.12
E-GEOD-93593	yes	12.88
E-ANND-3	no	1.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting GPC2, 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-3646	100.00	73.56	5283
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 6)

• Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). (PMID:28440309)
• these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target. (PMID:28898695)
• CAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice. (PMID:34195677)
• GPC2 Is a Potential Diagnostic, Immunological, and Prognostic Biomarker in Pan-Cancer. (PMID:35345673)
• Association between GPC2 polymorphisms and neuroblastoma risk in Chinese children. (PMID:36920409)
• GPC2 promotes prostate cancer progression via MDK-mediated activation of PI3K/AKT signaling pathway. (PMID:39014225)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpc2	ENSDARG00000104217
mus_musculus	Gpc2	ENSMUSG00000029510
rattus_norvegicus	Gpc2	ENSRNOG00000001367
drosophila_melanogaster	dlp	FBGN0041604

Paralogs (5): GPC1 (ENSG00000063660), GPC4 (ENSG00000076716), GPC3 (ENSG00000147257), GPC5 (ENSG00000179399), GPC6 (ENSG00000183098)

Protein

Protein identifiers

Glypican-2 — Q8N158 (reviewed: Q8N158)

All UniProt accessions (2): A0A0J9YXG7, Q8N158

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan that bears heparan sulfate. May fulfill a function related to the motile behaviors of developing neurons.

Subunit / interactions. Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2. Interacts (heparan sulfate chain) with MDK; this interaction is inhibited by heparin followed by chondroitin sulfate E; this interaction induces GPC2 clustering through heparan sulfate chain; this interaction induces neuronal cell adhesion and neurite outgrowth.

Subcellular location. Cell membrane Secreted. Extracellular space.

Similarity. Belongs to the glypican family.

RefSeq proteins (1): NP_689955* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001863	Glypican	Family
IPR019803	Glypican_CS	Conserved_site

Pfam: PF01153

UniProt features (42 total): helix 17, strand 7, glycosylation site 5, turn 4, chain 2, region of interest 2, signal peptide 1, sequence variant 1, propeptide 1, compositionally biased region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6WJL	X-RAY DIFFRACTION	3.3
7T62	ELECTRON MICROSCOPY	21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N158-F1	80.04	0.64

Antibody-complex structures (SAbDab): 2 — 6WJL, 7T62

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): 554

Glycosylation sites (5): 155, 500, 502, 55, 92

Function

Pathways and Gene Ontology

Reactome pathways

16 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-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-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: 112 (showing top): GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, GOBP_POSITIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOCC_LYSOSOMAL_LUMEN, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, TAATTA_CHX10_01

GO Biological Process (6): smoothened signaling pathway (GO:0007224), regulation of signal transduction (GO:0009966), positive regulation of neuron projection development (GO:0010976), cell migration (GO:0016477), neuron differentiation (GO:0030182), regulation of protein localization to membrane (GO:1905475)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), lysosomal lumen (GO:0043202), synapse (GO:0045202), side of membrane (GO:0098552), membrane (GO:0016020), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-9 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
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	4
membrane	2
cell surface receptor signaling pathway	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cell motility	1
cell differentiation	1
generation of neurons	1
regulation of protein localization	1
regulation of cellular localization	1
protein localization to membrane	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus	1
intracellular organelle lumen	1
cell periphery	1
lysosome	1
vacuolar lumen	1
cell junction	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPC2	MDK	P21741	791
GPC2	GPC3	P51654	716
GPC2	SDC3	O75056	605
GPC2	SDC2	P34741	601
GPC2	PTN	P21246	578
GPC2	SDC1	P18827	479
GPC2	GPC4	O75487	462
GPC2	HSPG2	P98160	454
GPC2	SDC4	P31431	448
GPC2	NDST3	O95803	442
GPC2	GLCE	O94923	440
GPC2	NDST2	P52849	439
GPC2	AGRN	O00468	438
GPC2	HS2ST1	Q7LGA3	426
GPC2	PGA4	P00790	425

IntAct

16 interactions, top by confidence:

A	B	Type	Score
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
Gpr158	AGRN	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
HADHB	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): GPC2 (Reconstituted Complex), GPC2 (Affinity Capture-MS), GPC2 (Affinity Capture-MS), GPC2 (Affinity Capture-MS), GPC2 (Affinity Capture-MS), GPC2 (Affinity Capture-MS), GPC2 (Affinity Capture-RNA), GPC2 (Affinity Capture-MS), GPC2 (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	85
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929826	GRCh37/hg19 7q22.1(chr7:99593346-102470275)x1	Likely pathogenic

SpliceAI

1312 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100171260:CCCG:C	donor_gain	1.0000
7:100171266:T:TA	donor_gain	1.0000
7:100171776:CA:C	donor_loss	1.0000
7:100171777:A:AC	donor_gain	1.0000
7:100171777:ACCAG:A	donor_gain	1.0000
7:100171778:C:CC	donor_gain	1.0000
7:100171778:C:CT	donor_loss	1.0000
7:100171778:CCAG:C	donor_gain	1.0000
7:100171778:CCAGC:C	donor_gain	1.0000
7:100171923:CAC:C	acceptor_gain	1.0000
7:100171926:C:CA	acceptor_loss	1.0000
7:100171927:T:G	acceptor_loss	1.0000
7:100172079:C:A	donor_gain	1.0000
7:100172086:C:CT	donor_loss	1.0000
7:100172105:A:AC	donor_gain	1.0000
7:100172106:C:CC	donor_gain	1.0000
7:100172213:ACCAT:A	acceptor_gain	1.0000
7:100172214:CCAT:C	acceptor_gain	1.0000
7:100172214:CCATC:C	acceptor_gain	1.0000
7:100172215:CAT:C	acceptor_gain	1.0000
7:100172215:CATCT:C	acceptor_gain	1.0000
7:100172216:AT:A	acceptor_gain	1.0000
7:100172217:TCTTA:T	acceptor_loss	1.0000
7:100172218:C:CC	acceptor_gain	1.0000
7:100172218:C:CG	acceptor_loss	1.0000
7:100172219:T:C	acceptor_gain	1.0000
7:100172219:T:TC	acceptor_gain	1.0000
7:100177028:CCTCA:C	donor_loss	1.0000
7:100177029:CTCAC:C	donor_loss	1.0000
7:100177030:TCACC:T	donor_loss	1.0000

AlphaMissense

3651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100171559:C:A	W430C	0.998
7:100171559:C:G	W430C	0.998
7:100173848:C:A	W293C	0.996
7:100173848:C:G	W293C	0.996
7:100171634:C:A	W405C	0.994
7:100171634:C:G	W405C	0.994
7:100173939:C:G	C263S	0.994
7:100173940:A:T	C263S	0.994
7:100176347:C:G	C62S	0.994
7:100176348:A:T	C62S	0.994
7:100176326:C:G	C69S	0.993
7:100176327:A:T	C69S	0.993
7:100171912:C:G	C346S	0.992
7:100171913:A:T	C346S	0.992
7:100172131:C:G	G327R	0.992
7:100173948:C:G	C260S	0.992
7:100173949:A:G	C260R	0.992
7:100173949:A:T	C260S	0.992
7:100176348:A:G	C62R	0.992
7:100175711:A:G	L170P	0.991
7:100176310:C:A	E74D	0.991
7:100176310:C:G	E74D	0.991
7:100176329:C:G	C68S	0.991
7:100176330:A:T	C68S	0.991
7:100176347:C:T	C62Y	0.991
7:100173899:G:C	C276W	0.990
7:100173912:C:T	C272Y	0.990
7:100177034:C:A	G56C	0.990
7:100172118:A:G	L331P	0.989
7:100173900:C:T	C276Y	0.989

dbSNP variants (sampled 300 via entrez): RS1000133510 (7:100178744 A>G), RS1000195303 (7:100176809 G>A,C,T), RS1000444312 (7:100170683 A>C,G), RS1000485949 (7:100179075 G>A), RS1000532578 (7:100175103 C>G), RS1000586580 (7:100175460 G>A), RS1001184521 (7:100169262 GCCATTGCACT>G), RS1001532546 (7:100175189 A>G), RS1001568685 (7:100174916 T>G), RS1002258936 (7:100173583 T>A,G), RS1002597686 (7:100177316 G>A), RS1002698598 (7:100169236 C>T), RS1002812191 (7:100169634 T>G), RS1003001511 (7:100172369 T>C), RS1003527727 (7:100178235 G>T)

Disease associations

OMIM: gene MIM:618446 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_259	Refractive error	3.000000e-16
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Valproic Acid	affects expression, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
exemestane	increases expression	1
CGP 52608	affects binding, increases reaction	1
dorsomorphin	decreases expression, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Ozone	affects expression, increases abundance	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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