GPRC5A
protein-codingG protein-coupled receptor class C group 5 member A, the group of G protein-coupled receptors, Class C orphans
Gene summary
This gene encodes a member of the type 3 G protein-coupling receptor family, characterized by the signature 7-transmembrane domain motif. The encoded protein may be involved in interaction between retinoid acid and G protein signalling pathways. Retinoic acid plays a critical role in development, cellular growth, and differentiation. This gene may play a role in embryonic development and epithelial cell differentiation. [provided by RefSeq, Jul 2008]
- RAI3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPRC5A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003979.4. 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 | 3 | 3 | 6 | |||
| missense | 56 | 4 | 1 | 61 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 7 | 1 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003970.1 | 3 | MANE Select | |
| Ensembl | ENSP00000014914.6 | 3 | MANE Select | |
| Ensembl | ENSP00000441627.1 | 1 | Standard | |
| Ensembl | ENSP00000439430.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Class C Metabotropic glutamate, pheromone
- EGFR1
Biological Process
- signal transduction
- negative regulation of epidermal growth factor-activated receptor activity
- G protein-coupled receptor signaling pathway
- activation of protein kinase activity
Molecular Function
- G protein-coupled receptor activity
- protein binding
- protein kinase activator activity
- cadherin binding
Cellular Component
- nucleolus
- plasma membrane
- integral component of plasma membrane
- cytoplasmic vesicle membrane
- vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000014914
- Coding exons
- 3
- Length
- 27156
- Individuals with no LoFs
- 125163
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 581
- Defined
- 125746
- p
- 0.00232
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.617 | 233 | 208 | 1.12 | 0.0000124 | 2323 |
| Missense (PolyPhen) | 81 | 74.079 | 1.0934 | 911 | ||
| Synonymous | -0.338 | 93 | 88.9 | 1.05 | 0.00000571 | 752 |
| Loss of Function | 0.000600 | 11 | 11.0 | 1.00 | 6.52e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00086 | rare |
| Latino/Admixed American | 0.00081 | 0.00081 | rare |
| Ashkenazi Jewish | 0.0032 | 0.0032 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.0012 | 0.0012 | notable |
| European (Non-Finnish) | 0.0039 | 0.0038 | notable |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.0023 | 0.0023 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218). {ECO:0000250|UniProtKB:Q8BHL4, ECO:0000269|PubMed:18000218}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.322
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.770
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |