GPC4

glypican 4, the group of Glypicans

Basic information

Region (hg38): X:133300102-133415489

Links

ENSG00000076716 ∙ NCBI:2239 ∙ OMIM:300168 ∙ HGNC:4452 ∙ Uniprot:O75487 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Keipert syndrome (Definitive), mode of inheritance: XLR
• Keipert syndrome (Moderate), mode of inheritance: AR
• Keipert syndrome (Definitive), mode of inheritance: XL
• Keipert syndrome (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Keipert syndrome (Nasodigitoacoustic syndrome)	XL	Audiologic/Otolaryngologic; Cardiovascular	In affected individuals, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with pulmonic stenosis (among other features), and awareness may allow prompt diagnosis and management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	30982611

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPC4 gene.

• not provided (36 variants)
• Keipert syndrome (10 variants)
• Inborn genetic diseases (10 variants)
• not specified (3 variants)
• GPC4-related condition (2 variants)
• Wilms tumor 1;Keipert syndrome;Simpson-Golabi-Behmel syndrome type 1 (1 variants)
• Distal shortening of limbs (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPC4 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				4		4
missense		1	30	3	2	36
nonsense	2	1				3
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	2	1	4
non coding					6	6
Total	3	2	31	7	8

Variants in GPC4

This is a list of pathogenic ClinVar variants found in the GPC4 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-133302915-G-C			Likely benign (Aug 01, 2023)
X-133302929-G-A		Keipert syndrome • GPC4-related disorder	Conflicting classifications of pathogenicity (Aug 28, 2023)
X-133302940-C-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
X-133302957-G-A			Likely benign (Dec 31, 2019)
X-133302977-T-C		Inborn genetic diseases	Uncertain significance (Mar 17, 2023)
X-133302983-C-A			Uncertain significance (Feb 27, 2022)
X-133302997-T-C		Inborn genetic diseases	Uncertain significance (Dec 15, 2022)
X-133303016-G-GGCAC		Keipert syndrome	Pathogenic (Feb 01, 2019)
X-133303022-G-A		Keipert syndrome	Pathogenic (Oct 02, 2019)
X-133303048-C-A			Uncertain significance (Apr 26, 2023)
X-133303052-C-A		Keipert syndrome	Pathogenic (Oct 02, 2019)
X-133303069-C-T		GPC4-related disorder	Uncertain significance (Apr 12, 2023)
X-133303073-G-A			Likely benign (Jul 21, 2018)
X-133303074-T-C			Uncertain significance (Feb 01, 2019)
X-133303076-T-TA			Benign (Aug 27, 2017)
X-133303171-T-C		Inborn genetic diseases	Uncertain significance (Jan 06, 2017)
X-133303187-C-T			Uncertain significance (Jul 15, 2022)
X-133303203-ATTC-A		Keipert syndrome	Uncertain significance (May 06, 2021)
X-133303222-A-G			Uncertain significance (Feb 19, 2023)
X-133303282-T-C			Uncertain significance (Mar 11, 2023)
X-133303309-G-A		Keipert syndrome	Benign (Aug 10, 2021)
X-133304736-T-C			Likely benign (-)
X-133304741-C-T			Uncertain significance (Mar 27, 2023)
X-133304782-C-T		Distal shortening of limbs	Likely pathogenic (Jun 01, 2017)
X-133304789-C-T		Inborn genetic diseases	Uncertain significance (Feb 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPC4	protein_coding	protein_coding	ENST00000370828	9	115388

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.926	0.0739	125640	3	0	125643	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	159	230	0.693	0.0000182	3706
Missense in Polyphen		40	95.762	0.4177		1585
Synonymous	0.552	82	88.6	0.925	0.00000726	1031
Loss of Function	3.39	2	17.1	0.117	0.00000129	291

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000365	0.0000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000246	0.0000176
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. May be involved in the development of kidney tubules and of the central nervous system (By similarity). {ECO:0000250}.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway;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;Integrin;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.160

Intolerance Scores

• loftool: 0.0928
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.35

Haploinsufficiency Scores

• pHI: 0.875
• hipred: Y
• hipred_score: 0.642
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.758

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Gpc4
• Phenotype: hematopoietic system phenotype

Zebrafish Information Network

• Gene name: gpc4
• Affected structure: slow muscle cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: retinoid metabolic process;glycosaminoglycan biosynthetic process;glycosaminoglycan catabolic process;regulation of signal transduction;Wnt signaling pathway, planar cell polarity pathway;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane;synaptic membrane adhesion;regulation of presynapse assembly
• Cellular component: nucleus;Golgi lumen;plasma membrane;external side of plasma membrane;lysosomal lumen;collagen-containing extracellular matrix;extracellular exosome;glutamatergic synapse;anchored component of presynaptic membrane
• Molecular function: coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway