GPC3

glypican 3, the group of Glypicans

Basic information

Region (hg38): X:133535745-133987100

Previous symbols: [ "SDYS" ]

Links

ENSG00000147257 ∙ NCBI:2719 ∙ OMIM:300037 ∙ HGNC:4451 ∙ Uniprot:P51654 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Simpson-Golabi-Behmel syndrome type 1 (Definitive), mode of inheritance: XLR
• Simpson-Golabi-Behmel syndrome type 1 (Strong), mode of inheritance: XL
• Simpson-Golabi-Behmel syndrome type 1 (Definitive), mode of inheritance: XL
• Simpson-Golabi-Behmel syndrome (Supportive), mode of inheritance: XL
• Simpson-Golabi-Behmel syndrome type 1 (Definitive), mode of inheritance: XL
• Simpson-Golabi-Behmel syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Simpson-Golabi-Behmel syndrome, type 1	XL	Cardiovascular; Oncologic	The disorder, which can include certain types of tumors, should be clinically recognizable, but surveillance for neoplasms may allow early diagnosis and treatment, which may ameliorate morbidity and mortality; Awareness of the risk of cardiac sequelae, which can include anatomic anomalies and dysrhythmias, may allow prompt detection and management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	1227524; 6490008; 6538755; 3177455; 1479609; 7909248; 8589713; 9950367; 10232747; 11477610; 16158429; 17850639; 17603795; 18203194; 2018065; 20301398; 20950395; 21434539; 21362501; 22807161; 23463737; 23606591

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPC3 gene.

• Wilms tumor 1 (23 variants)
• not provided (10 variants)
• Simpson-Golabi-Behmel syndrome type 1 (4 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPC3 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			3	185	17	205
missense		2	399	48	11	460
nonsense	13	4				17
start loss						0
frameshift	15	4	1			20
inframe indel			11			11
splice donor/acceptor (+/-2bp)	3	6				9
splice region			18	27	1	46
non coding			3	67	17	87
Total	31	16	417	300	45

Variants in GPC3

This is a list of pathogenic ClinVar variants found in the GPC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-133535890-TTTTC-T			Benign (Jul 03, 2018)
X-133536125-C-A		Wilms tumor 1	Uncertain significance (Mar 23, 2023)
X-133536128-T-C		Wilms tumor 1	Uncertain significance (Aug 17, 2019)
X-133536128-T-G		Wilms tumor 1	Uncertain significance (Apr 07, 2023)
X-133536129-G-A		Wilms tumor 1	Uncertain significance (Nov 28, 2016)
X-133536129-GCA-G		Simpson-Golabi-Behmel syndrome type 1	Uncertain significance (Mar 24, 2022)
X-133536130-C-G		Wilms tumor 1	Likely benign (Jan 30, 2023)
X-133536130-C-T		Wilms tumor 1	Likely benign (Nov 11, 2017)
X-133536131-A-C		Wilms tumor 1	Uncertain significance (Nov 01, 2023)
X-133536132-C-T		Wilms tumor 1	Uncertain significance (Sep 27, 2023)
X-133536133-C-T		Wilms tumor 1	Uncertain significance (Oct 16, 2021)
X-133536135-GGAA-G		Wilms tumor 1	Uncertain significance (Nov 17, 2023)
X-133536136-G-A		Wilms tumor 1	Likely benign (Mar 07, 2023)
X-133536138-A-G		Wilms tumor 1	Uncertain significance (Dec 20, 2019)
X-133536142-G-A		Wilms tumor 1	Likely benign (Oct 21, 2022)
X-133536143-A-C		Wilms tumor 1	Conflicting classifications of pathogenicity (Aug 05, 2023)
X-133536146-C-G		Hereditary cancer-predisposing syndrome	Uncertain significance (Apr 30, 2021)
X-133536148-C-T		Wilms tumor 1	Likely benign (May 28, 2023)
X-133536149-A-G		Wilms tumor 1	Uncertain significance (May 19, 2022)
X-133536151-C-G		Wilms tumor 1	Benign (Dec 25, 2023)
X-133536153-C-A		Wilms tumor 1	Uncertain significance (Nov 17, 2019)
X-133536153-C-T		Wilms tumor 1	Uncertain significance (Aug 01, 2021)
X-133536154-C-T		Wilms tumor 1 • GPC3-related disorder	Likely benign (Nov 06, 2023)
X-133536155-G-A		Wilms tumor 1	Uncertain significance (Oct 13, 2022)
X-133536156-A-G		Wilms tumor 1	Uncertain significance (Mar 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPC3	protein_coding	protein_coding	ENST00000394299	9	450150

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00180	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	161	222	0.726	0.0000161	4011
Missense in Polyphen		23	50.406	0.45629		948
Synonymous	0.0378	87	87.5	0.995	0.00000676	1121
Loss of Function	3.98	0	18.4	0.00	0.00000148	321

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cell surface proteoglycan that bears heparan sulfate (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (By similarity). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (By similarity). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (PubMed:16227623, PubMed:24496449). Positively regulates the non-canonical Wnt signaling pathway (By similarity). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Inhibits the dipeptidyl peptidase activity of DPP4 (PubMed:17549790). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (By similarity). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (By similarity). Required for coronary vascular development (By similarity). Plays a role in regulating cell movements during gastrulation (By similarity). {ECO:0000250|UniProtKB:Q6V9Y8, ECO:0000250|UniProtKB:Q8CFZ4, ECO:0000269|PubMed:14610063, ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:17549790, ECO:0000269|PubMed:24496449}.
• Disease: DISEASE: Simpson-Golabi-Behmel syndrome 1 (SGBS1) [MIM:312870]: A condition characterized by pre- and postnatal overgrowth (gigantism), facial dysmorphism and a variety of inconstant visceral and skeletal malformations. Characteristic dysmorphic features include macrocephaly with coarse, distinctive facies with a large protruding jaw, broad nasal bridge and cleft palate. Cardiac defects are frequent. {ECO:0000269|PubMed:10814714}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteoglycans in cancer - Homo sapiens (human);WNT-Ncore;HH-Ncore;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism of carbohydrates;Post-translational protein phosphorylation;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;Post-translational protein modification;Metabolism of proteins;Metabolism;Metabolism of vitamins and cofactors;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling;Glypican 3 network (Consensus)

Recessive Scores

• pRec: 0.362

Intolerance Scores

• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.19

Haploinsufficiency Scores

• pHI: 0.781
• hipred: Y
• hipred_score: 0.669
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.893

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gpc3
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; pigmentation phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype

Gene ontology

• Biological process: retinoid metabolic process;branching involved in ureteric bud morphogenesis;glycosaminoglycan biosynthetic process;glycosaminoglycan catabolic process;response to bacterium;anatomical structure morphogenesis;anterior/posterior axis specification;body morphogenesis;negative regulation of peptidase activity;bone mineralization;osteoclast differentiation;lung development;positive regulation of BMP signaling pathway;embryonic hindlimb morphogenesis;cell migration involved in gastrulation;post-translational protein modification;cellular protein metabolic process;positive regulation of protein catabolic process;positive regulation of endocytosis;negative regulation of smoothened signaling pathway;positive regulation of smoothened signaling pathway;negative regulation of growth;positive regulation of glucose import;negative regulation of epithelial cell proliferation;regulation of canonical Wnt signaling pathway;coronary vasculature development;cell proliferation involved in kidney development;mesenchymal cell proliferation involved in ureteric bud development;mesonephric duct morphogenesis;cell proliferation involved in metanephros development;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;regulation of non-canonical Wnt signaling pathway;positive regulation of Wnt signaling pathway, planar cell polarity pathway
• Cellular component: endoplasmic reticulum lumen;Golgi lumen;plasma membrane;intrinsic component of plasma membrane;lysosomal lumen;anchored component of plasma membrane;collagen-containing extracellular matrix
• Molecular function: protein binding;peptidyl-dipeptidase inhibitor activity