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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GPC6
glypican 6
Chromosome 13 Β· 13q31.3-q32.1
NCBI Gene: 10082Ensembl: ENSG00000183098.12HGNC: HGNC:4454UniProt: Q9Y625
57PubMed Papers
21Diseases
0Drugs
9Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleusprotein bindingcell migrationextracellular matrixautosomal recessive omodysplasiaCOVID-19dengue diseasesmoking initiation
✦AI Summary

GPC6 (glypican 6) is a cell surface heparan sulfate proteoglycan anchored to the plasma membrane by a glycosyl-phosphatidylinositol linkage 1. As a member of the glypican family, GPC6 primarily functions as a coreceptor regulating growth factor signaling pathways, particularly Wnt, Hedgehog, fibroblast growth factors, and bone morphogenetic proteins 1. The protein can facilitate Wnt signaling by stabilizing interactions between Wnts and their Frizzled receptors, and this regulatory activity is only partially dependent on heparan sulfate chains 1. GPC6 demonstrates tissue-specific expression, being most abundant in ovary, liver, and kidney 2. The gene is located on chromosome 13 in a tandem cluster with GPC5, forming one of the largest human genes at approximately 1-2 Mb 3. Clinically, GPC6 is associated with omodysplasia-1, a skeletal dysplasia caused by loss-of-function variants that impair bone growth through reduced Hedgehog signaling activity 4. Additionally, GPC6 expression correlates with CD8+ T-lymphocyte infiltration in early-stage ovarian cancer and serves as a favorable prognostic marker for patient survival 5. The protein has also been implicated in Alzheimer disease risk in African American populations 6.

Sources cited
1
GPC6 is a GPI-anchored heparan sulfate proteoglycan that regulates Wnt, Hedgehog, FGF, and BMP signaling pathways
PMID: 18505598
2
GPC6 encodes a 554 amino acid protein most highly expressed in ovary, liver, and kidney
PMID: 10329016
3
GPC6 is located on chromosome 13q32 in tandem with GPC5 and is one of the largest human genes
PMID: 11566272
4
Loss-of-function variants in GPC6 cause omodysplasia-1 skeletal dysplasia through impaired Hedgehog signaling
PMID: 37353964
5
GPC6 expression correlates with CD8+ T-cell infiltration and improved survival in early-stage ovarian cancer
PMID: 26448945
6
GPC6 variants are associated with Alzheimer disease risk in African American populations
PMID: 33074286
Disease Associationsβ“˜21
autosomal recessive omodysplasiaOpen Targets
0.75Strong
COVID-19Open Targets
0.54Moderate
dengue diseaseOpen Targets
0.46Moderate
smoking initiationOpen Targets
0.41Moderate
omodysplasiaOpen Targets
0.41Moderate
refractive errorOpen Targets
0.40Weak
alcohol drinkingOpen Targets
0.40Weak
insomniaOpen Targets
0.40Weak
Abnormality of the skeletal systemOpen Targets
0.35Weak
Abnormality of refractionOpen Targets
0.33Weak
major depressive disorderOpen Targets
0.31Weak
Lower limb asymmetryOpen Targets
0.29Weak
chronic laryngitisOpen Targets
0.29Weak
femur fractureOpen Targets
0.28Weak
narcolepsyOpen Targets
0.28Weak
pernicious anemiaOpen Targets
0.28Weak
Tietze syndromeOpen Targets
0.27Weak
type 2 diabetes mellitusOpen Targets
0.27Weak
bone remodeling diseaseOpen Targets
0.25Weak
protozoa infectious diseaseOpen Targets
0.25Weak
Omodysplasia 1UniProt
Pathogenic Variants9
NM_005708.5(GPC6):c.511C>T (p.Arg171Trp)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 171
NM_005708.5(GPC6):c.433_451del (p.Glu145fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 145
NC_000013.11:g.94252984_94352299del99316insCTAPathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009
NM_005708.5(GPC6):c.700C>T (p.Arg234Ter)Pathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009β†’ Residue 234
NM_005708.5(GPC6):c.778del (p.Leu260fs)Pathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009β†’ Residue 260
NM_005708.3(GPC6):c.320_711delPathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009
NM_005708.3(GPC6):c.320_711delPathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009
NM_005708.3(GPC6):c.712_877dupPathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009
NC_000013.11:g.93997007_94063501del66495insATAAATCACTTAGAGATGTPathogenic
Autosomal recessive omodysplasia
β˜†β˜†β˜†β˜†2009
View on ClinVar β†—
Related Genes
SDC2Protein interaction78%GPC4Protein interaction67%GPC5Protein interaction56%GPC2Shared pathway33%TMEM18Shared pathway33%LRRIQ1Shared pathway33%
Tissue Expression6 tissues
Liver
100%
Brain
63%
Ovary
49%
Heart
44%
Lung
20%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
GPC6SDC2GPC4GPC5GPC2TMEM18LRRIQ1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9Y625
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.38Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.24 [0.16–0.38]
RankingsWhere GPC6 stands among ~20K protein-coding genes
  • #7,966of 20,598
    Most Researched57
  • #2,962of 5,498
    Most Pathogenic Variants9
  • #1,865of 17,882
    Most Constrained (LOEUF)0.38 Β· top quartile
Genes detectedGPC6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Glypicans.
PMID: 18505598
Genome Biol Β· 2008
1.00
2
Wnt3a-Loaded Extracellular Vesicles Promote Alveolar Epithelial Regeneration after Lung Injury.
PMID: 37072558
Adv Sci (Weinh) Β· 2023
0.90
3
GPC6, a novel member of the glypican gene family, encodes a product structurally related to GPC4 and is colocalized with GPC5 on human chromosome 13.
PMID: 10329016
Genomics Β· 1999
0.80
4
A 4-Mb BAC/PAC contig and complete genomic structure of the GPC5/GPC6 gene cluster on chromosome 13q32.
PMID: 11566272
Matrix Biol Β· 2001
0.70
5
Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis.
PMID: 33074286
JAMA Neurol Β· 2021
0.60