GPC3 glypican 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GPC3provided by HGNC
Official Full Name: glypican 3provided by HGNC
Primary source: HGNC:HGNC:4451
See related: Ensembl:ENSG00000147257 MIM:300037
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SGB; DGSX; MXR7; SDYS; SGBS; OCI-5; SGBS1; GTR2-2
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. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
Expression: Biased expression in placenta (RPKM 205.3), lung (RPKM 44.2) and 3 other tissues See more
Orthologs: mouse all
NEW: Try the new Data Table view

Genomic context

Location:: Xq26.2

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (133535745..133985616, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (132669773..133119673, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression.
Title: Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression.
High glypican-3 expression characterizes a distinct subset of ovarian clear cell carcinomas in Canadian patients: an opportunity for targeted therapy.
Title: High glypican-3 expression characterizes a distinct subset of ovarian clear cell carcinomas in Canadian patients: an opportunity for targeted therapy.
rs2267531, a promoter SNP within glypican-3 gene in the X chromosome, is associated with hepatocellular carcinoma in Egyptians.
Title: rs2267531, a promoter SNP within glypican-3 gene in the X chromosome, is associated with hepatocellular carcinoma in Egyptians.
Intratumoral reciprocal expression of monocarboxylate transporter 4 and glypican-3 in hepatocellular carcinomas.
Title: Intratumoral reciprocal expression of monocarboxylate transporter 4 and glypican-3 in hepatocellular carcinomas.
the present study demonstrates that up-regulation of GPC3 accelerates the progression of lung squamous cell carcinoma (SCC) in a b-catenin-dependent manner. Our study provides a theoretical basis for GPC3/b-catenin as a novel diagnostic marker and therapeutic target for lung SCC
Title: Glypican-3 promotes cell proliferation and tumorigenesis through up-regulation of β-catenin expression in lung squamous cell carcinoma.
In biopsy specimens of hepatocellular carcinoma, RGS5 and GPC3 expression were useful molecular makers for predicting portal vein invasion
Title: Usefulness of Tumor Tissue Biopsy for Predicting the Biological Behavior of Hepatocellular Carcinoma.
Up-regulation of glypican-3 and alpha-smooth muscle actin mRNA expression was observed in biliary atresia livers, and it was positively associated with with poor outcomes after successful portoenterostomy. Moreover, glypican-3 and alpha-smooth muscle actin expressions were positively associated with fibrosis stage in biliary atresia livers.
Title: Hepatic glypican-3 and alpha-smooth muscle actin overexpressions reflect severity of liver fibrosis and predict outcome after successful portoenterostomy in biliary atresia.
Provides a strong line of evidence for GPC3 as an important therapeutic target.
Title: Glypican-3 Enhances Reprogramming of Glucose Metabolism in Liver Cancer Cells.
expression significantly reduced in first-trimester small for gestational age as well as in the third-trimester fetal growth restriction placentae compared to controls
Title: Decreased placental glypican expression is associated with human fetal growth restriction.
Results found that levels of plasma GPC3 could enable predicting intratumoral GPC3 expression in patients with HCV-related hepatocellular carcinomas.
Title: Plasma and tumoral glypican-3 levels are correlated in patients with hepatitis C virus-related hepatocellular carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (182)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. GeneReviews: Not available
Simpson-Golabi-Behmel syndrome type 1 MedGen: C0796154 OMIM: 312870 GeneReviews: Simpson-Golabi-Behmel Syndrome Type 1, Wilms Tumor Predisposition	Compare labs
Wilms tumor 1 MedGen: CN033288 OMIM: 194070 GeneReviews: Wilms Tumor Predisposition, PAX6-Related Aniridia, WT1 Disorder	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2012-04-26) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2012-04-26) ClinGen Genome Curation Page

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH16248 (e-PCR)
- UniSTS:75008

SHGC-52514 (e-PCR)
- UniSTS:11019

L77881 (e-PCR)
- UniSTS:44043

RH79181 (e-PCR)
- UniSTS:24

AL032559 (e-PCR)
- UniSTS:93210

DXS1414 (e-PCR)
- UniSTS:148771

L77880 (e-PCR)
- UniSTS:3642

DXS7764 (e-PCR)
- UniSTS:37434

NoName (e-PCR)
- UniSTS:99645

AL032585 (e-PCR)
- UniSTS:93260

G33003 (e-PCR)
- UniSTS:117580

AL032586 (e-PCR)
- UniSTS:93261

RH18522 (e-PCR)
- UniSTS:10581

AL008948 (e-PCR)
- UniSTS:72801

L76269 (e-PCR)
- UniSTS:47713

DXS9777 (e-PCR)
- UniSTS:18029

DXS7596 (e-PCR)
- UniSTS:75126

SHGC-35437 (e-PCR)
- UniSTS:58492

DXS7315 (e-PCR)
- UniSTS:39065

WI-16747 (e-PCR)
- UniSTS:38043

A009Z03 (e-PCR)
- UniSTS:5021

RH70004 (e-PCR)
- UniSTS:31416

SHGC-34872 (e-PCR)
- UniSTS:30914

DXS6842 (e-PCR)
- UniSTS:99778

RH17563 (e-PCR)
- UniSTS:37314

SHGC-35150 (e-PCR)
- UniSTS:81091

G66652 (e-PCR)
- UniSTS:166853

G66657 (e-PCR)
- UniSTS:166856

RH36204 (e-PCR)
- UniSTS:26313

G66656 (e-PCR)
- UniSTS:166858

G66651 (e-PCR)
- UniSTS:166859

DXS7314 (e-PCR)
- UniSTS:20177

L77882 (e-PCR)
- UniSTS:4819

L47619 (e-PCR)
- UniSTS:53459

RH68769 (e-PCR)
- UniSTS:48342

L77883 (e-PCR)
- UniSTS:18904

AL008945 (e-PCR)
- UniSTS:23776

SHGC-34460 (e-PCR)
- UniSTS:29920

G66688 (e-PCR)
- UniSTS:166883

G66690 (e-PCR)
- UniSTS:166885

G66691 (e-PCR)
- UniSTS:166886

G66692 (e-PCR)
- UniSTS:166889

RH45404 (e-PCR)
- UniSTS:54249

G18198 (e-PCR)
- UniSTS:1003

STS-H93110 (e-PCR)
- UniSTS:74476

L77878 (e-PCR)
- UniSTS:48364

L77879 (e-PCR)
- UniSTS:23277

GDB:182527 (e-PCR)
- UniSTS:155386

Homology

Homologs of the GPC3 gene: The GPC3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 251 organisms have orthologs with human gene GPC3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
peptidyl-dipeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
anterior/posterior axis specification	IEA Inferred from Electronic Annotation more info
body morphogenesis	IEA Inferred from Electronic Annotation more info
bone mineralization	IEA Inferred from Electronic Annotation more info
branching involved in ureteric bud morphogenesis	IEA Inferred from Electronic Annotation more info
cell migration	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell migration involved in gastrulation	ISS Inferred from Sequence or Structural Similarity more info
cell proliferation involved in kidney development	ISS Inferred from Sequence or Structural Similarity more info
cell proliferation involved in metanephros development	IEA Inferred from Electronic Annotation more info
cellular protein metabolic process	TAS Traceable Author Statement more info
coronary vasculature development	ISS Inferred from Sequence or Structural Similarity more info
embryonic hindlimb morphogenesis	IEA Inferred from Electronic Annotation more info
glycosaminoglycan biosynthetic process	TAS Traceable Author Statement more info
glycosaminoglycan catabolic process	TAS Traceable Author Statement more info
lung development	IEA Inferred from Electronic Annotation more info
mesenchymal cell proliferation involved in ureteric bud development	ISS Inferred from Sequence or Structural Similarity more info
mesonephric duct morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of growth	IEA Inferred from Electronic Annotation more info
negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info
negative regulation of smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
osteoclast differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of Wnt signaling pathway, planar cell polarity pathway	IEA Inferred from Electronic Annotation more info
positive regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endocytosis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of glucose import	IEA Inferred from Electronic Annotation more info
positive regulation of protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
post-translational protein modification	TAS Traceable Author Statement more info
regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
regulation of non-canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
regulation of protein localization to membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to bacterium	IEA Inferred from Electronic Annotation more info
retinoid metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi lumen	TAS Traceable Author Statement more info
anchored component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
anchored component of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
cell surface	IBA Inferred from Biological aspect of Ancestor more info	PubMed
collagen-containing extracellular matrix	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
extracellular region	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intrinsic component of plasma membrane	TAS Traceable Author Statement more info
lysosomal lumen	TAS Traceable Author Statement more info
plasma membrane	IDA Inferred from Direct Assay more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: glypican-3

Names: glypican proteoglycan 3; heparan sulphate proteoglycan; intestinal protein OCI-5; secreted glypican-3

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Data Table view

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009286.1 RefSeqGene

Range

4994..454894

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_505

mRNA and Protein(s)

NM_001164617.2 → NP_001158089.1 glypican-3 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK222766, AL009174, BX329946, DB107651, DQ349138

Consensus CDS

CCDS55496.1

UniProtKB/Swiss-Prot

P51654

UniProtKB/TrEMBL

Q53H15

Related

ENSP00000377836.2, ENST00000394299.7

Conserved Domains (1) summary

pfam01153
Location:14 → 600

Glypican; Glypican
NM_001164618.2 → NP_001158090.1 glypican-3 isoform 3 precursor

See identical proteins and their annotated locations for NP_001158090.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region and lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1.

Source sequence(s)

AK222766, AK300168

UniProtKB/TrEMBL

B4DTD8, Q53H15

Conserved Domains (1) summary

pfam01153
Location:14 → 561

Glypican; Glypican
NM_001164619.2 → NP_001158091.1 glypican-3 isoform 4 precursor

See identical proteins and their annotated locations for NP_001158091.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon in both the 5' and central coding regions, compared to variant 1, resulting in an isoform (4) that is shorter than isoform 1.

Source sequence(s)

AK222766, AL009174, BX329946, DB107651, DQ349136

Consensus CDS

CCDS55495.1

UniProtKB/Swiss-Prot

P51654

UniProtKB/TrEMBL

Q53H15

Related

ENSP00000486325.1, ENST00000631057.2

Conserved Domains (1) summary

pfam01153
Location:14 → 523

Glypican; Glypican
NM_004484.4 → NP_004475.1 glypican-3 isoform 2 precursor

See identical proteins and their annotated locations for NP_004475.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.

Source sequence(s)

AK222766, DB107651, L47176

Consensus CDS

CCDS14638.1

UniProtKB/Swiss-Prot

P51654

UniProtKB/TrEMBL

I6QTG3, Q53H15

Related

ENSP00000359854.3, ENST00000370818.8

Conserved Domains (1) summary

pfam01153
Location:14 → 577

Glypican; Glypican