GPR18
protein-codingG protein-coupled receptor 18, the group of G protein-coupled receptors, Class A orphans
Gene summary
Enables G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within T cell differentiation; negative regulation of leukocyte chemotaxis; and negative regulation of tumor necrosis factor production. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.0 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 GPR18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001098200.2. 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 | 1 | 1 | ||||
| missense | 47 | 3 | 50 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 47 | 4 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001091670.1 | 1 | MANE Select | |
| Ensembl | ENSP00000380610.2 | 1 | MANE Select | |
| RefSeq | NP_005283.1 | 1 | Standard | |
| Ensembl | ENSP00000343428.3 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Other
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
- Class A/1 (Rhodopsin-like receptors)
Biological Process
- CD8-positive, alpha-beta intraepithelial T cell differentiation
- CD8-positive, gamma-delta intraepithelial T cell differentiation
- negative regulation of leukocyte chemotaxis
- G protein-coupled receptor signaling pathway
- negative regulation of tumor necrosis factor production
Molecular Function
- G protein-coupled receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
- cytoplasmic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340807
- Coding exons
- 1
- Length
- 7031
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125744
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.423 | 176 | 193 | 0.914 | 0.0000107 | 2178 |
| Missense (PolyPhen) | 54 | 71.902 | 0.75103 | 817 | ||
| Synonymous | -1.11 | 89 | 76.6 | 1.16 | 0.00000478 | 654 |
| Loss of Function | -0.603 | 13 | 10.9 | 1.20 | 7.22e-7 | 115 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for endocannabinoid N-arachidonyl glycine (NAGly) (PubMed:16844083, PubMed:24762058, PubMed:27572937). However, conflicting results about the role of NAGly as an agonist are reported (PubMed:27018161). Can also be activated by plant- derived and synthetic cannabinoid agonists (PubMed:24762058). The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase (PubMed:16844083). May contribute to regulation of the immune system. Is required for normal homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs)in small intstine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant (By similarity). Plays a role in hypotensive responses, mediating reduction in intraocular and blood pressure (By similarity). Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis (PubMed:27572937). {ECO:0000250|UniProtKB:Q8K1Z6, ECO:0000269|PubMed:16844083, ECO:0000269|PubMed:24762058, ECO:0000269|PubMed:27572937}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.922
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.445
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |