GPC4
protein-codingglypican 4, the group of Glypicans
Gene 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 GPC4 gene is adjacent to the 3' end of GPC3 and may also play a role in Simpson-Golabi-Behmel syndrome. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~115.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0009720
Submitter: Ambry Genetics
Inheritance Pattern: XL
Disease ID:MONDO:0009720
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0009720
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XLR
Disease ID:MONDO:0009720
Submitter: Ambry Genetics
Inheritance Pattern: XL
Disease ID:MONDO:0009720
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic
Intervention: Audiologic/Otolaryngologic; Cardiovascular
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001448.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 24 | 10 | 34 | |||
| missense | 2 | 138 | 12 | 152 | ||
| nonsense | 2 | 7 | 6 | 15 | ||
| start loss | 0 | |||||
| frameshift | 5 | 4 | 9 | |||
| splice donor/acceptor (+/-2bp) | 25 | 25 | ||||
| Total | 7 | 13 | 193 | 22 | 0 | 235 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001439.2 | 9 | MANE Select | |
| Ensembl | ENSP00000359864.3 | 9 | MANE Select | |
| Ensembl | ENSP00000557877.1 | 9 | Standard | |
| Ensembl | ENSP00000557877.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gpc4 | Danio rerio | Structure: slow muscle cell Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Wnt signaling pathway - Homo sapiens (human)
- Wnt Signaling Pathway
- Signaling by GPCR
- Signal Transduction
- Metabolism of fat-soluble vitamins
Biological Process
- retinoid metabolic process
- glycosaminoglycan biosynthetic process
- glycosaminoglycan catabolic process
- regulation of signal transduction
- Wnt signaling pathway, planar cell polarity pathway
Molecular Function
- coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway
Cellular Component
- nucleus
- Golgi lumen
- plasma membrane
- external side of plasma membrane
- lysosomal lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370828
- Coding exons
- 9
- Length
- 115388
- Individuals with no LoFs
- 125640
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 0
- Defined
- 125643
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 159 | 230 | 0.693 | 0.0000182 | 3706 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000037 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000025 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.160
Intolerance Scores
- LoFtool
- 0.0928
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.758
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |