GPR65
protein-codingG protein-coupled receptor 65, the group of G protein-coupled receptors, Class A orphans
Gene summary
Enables G protein-coupled receptor activity. Involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway; cellular response to acidic pH; and positive regulation of stress fiber assembly. Is active in early endosome membrane; late endosome membrane; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.7 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 GPR65 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003608.4. 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 | 0 | |||||
| missense | 32 | 3 | 35 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 32 | 3 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003599.2 | 1 | MANE Select | |
| Ensembl | ENSP00000267549.3 | 1 | MANE Select | |
| Ensembl | ENSP00000575224.1 | 1 | Standard | |
| Ensembl | ENSP00000575224.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gpr65 | Danio rerio | Structure: hemopoiesis Quality: increased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
- Class A/1 (Rhodopsin-like receptors)
- GPCR ligand binding
Biological Process
- apoptotic process
- immune response
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- multicellular organism development
Molecular Function
- G protein-coupled receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000267549
- Coding exons
- 1
- Length
- 6952
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125722
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.704 | 151 | 177 | 0.851 | 0.00000928 | 2222 |
| Missense (PolyPhen) | 50 | 64.869 | 0.77078 | 856 | ||
| Synonymous | 0.503 | 63 | 68.3 | 0.923 | 0.00000369 | 635 |
| Loss of Function | 1.92 | 3 | 9.31 | 0.322 | 4.84e-7 | 135 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00025 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000035 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (PubMed:11309421). Plays a role in immune response by maintaining lysosome function and supporting phagocytosis-mediated intracellular bacteria clearance (PubMed:27287411). May have a role in activation-induced cell death or differentiation of T-cells (By similarity). {ECO:0000250|UniProtKB:Q61038, ECO:0000269|PubMed:11309421, ECO:0000269|PubMed:27287411}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.511
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00562
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |