GPC6

glypican 6, the group of Glypicans

Basic information

Region (hg38): 13:93226807-94408020

Links

ENSG00000183098

∙ NCBI:10082 ∙ OMIM:604404 ∙ HGNC:4454 ∙ Uniprot:Q9Y625 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive omodysplasia (Strong), mode of inheritance: AR
autosomal recessive omodysplasia (Moderate), mode of inheritance: AR
autosomal recessive omodysplasia (Supportive), mode of inheritance: AR
autosomal recessive omodysplasia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Omodysplasia 1	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	19481194

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPC6 gene.

not_provided (140 variants)
Inborn_genetic_diseases (71 variants)
Autosomal_recessive_omodysplasia (37 variants)
GPC6-related_disorder (6 variants)
not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPC6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005708.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	47 clinvar	3 clinvar	55
missense	1 clinvar		111 clinvar	3 clinvar	3 clinvar	118
nonsense	1 clinvar					1
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)						0
Total	4	0	116	50	6

Highest pathogenic variant AF is 0.0000563908

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPC6	protein_coding	protein_coding	ENST00000377047	9	1180561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.142	0.858	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.901	276	321	0.859	0.0000185	3665
Missense in Polyphen		51	92.25	0.55284		1051
Synonymous	-1.17	136	120	1.14	0.00000680	1062
Loss of Function	3.31	6	23.2	0.259	0.00000116	278

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases (By similarity). Enhances migration and invasion of cancer cells through WNT5A signaling. {ECO:0000250, ECO:0000269|PubMed:21871017}.;
Disease: DISEASE: Omodysplasia 1 (OMOD1) [MIM:258315]: A rare autosomal recessive skeletal dysplasia characterized by facial dysmorphism and severe congenital micromelia with shortening and distal tapering of the humeri and femora, to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin. {ECO:0000269|PubMed:19481194}. Note=The disease is caused by mutations affecting the gene represented in this entry. Point mutations leading to protein truncation, as well as larger genomic rearrangements resulting in exon deletions, have been found in family segregating omodysplasia type 1. All mutations identified in individuals affected by omodysplasia could lead to the absence of a functional protein, the mutant RNAs being suspected to be nonsense-mediated mRNA decay (NMD) targets. Even if the mRNA escapes NMD and is translated, all mutations are expected to disrupt the three-dimensional protein structure and often to abolish multiple highly conserved cysteine residues.;
Pathway: miR-509-3p alteration of YAP1-ECM axis;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism of carbohydrates;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;Metabolism;Metabolism of vitamins and cofactors;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Intolerance Scores

loftool: 0.417
rvis_EVS: 0.02
rvis_percentile_EVS: 55.61

Haploinsufficiency Scores

pHI: 0.685
hipred: Y
hipred_score: 0.605
ghis: 0.519

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.579

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Gpc6
Phenotype: limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; respiratory 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); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype;

Gene ontology

Biological process: retinoid metabolic process;glycosaminoglycan biosynthetic process;glycosaminoglycan catabolic process;regulation of signal transduction;cell migration;Wnt signaling pathway, planar cell polarity pathway;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
Cellular component: extracellular space;nucleus;Golgi lumen;plasma membrane;lysosomal lumen;anchored component of plasma membrane;collagen-containing extracellular matrix;glutamatergic synapse
Molecular function: protein binding;coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway