GPR18

G protein-coupled receptor 18, the group of G protein-coupled receptors, Class A orphans

Basic information

Region (hg38): 13:99254731-99261744

Links

ENSG00000125245 ∙ NCBI:2841 ∙ OMIM:602042 ∙ HGNC:4472 ∙ Uniprot:Q14330 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPR18 gene.

• Inborn genetic diseases (14 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPR18 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						0
missense			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	1	0

Variants in GPR18

This is a list of pathogenic ClinVar variants found in the GPR18 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-99254885-T-G		not specified	Uncertain significance (Apr 28, 2023)
13-99254926-C-A		not specified	Uncertain significance (Aug 28, 2023)
13-99254941-C-A		not specified	Uncertain significance (Dec 01, 2022)
13-99254970-C-T		not specified	Uncertain significance (Jun 28, 2022)
13-99254986-C-T		not specified	Uncertain significance (Dec 16, 2023)
13-99255034-C-G		not specified	Uncertain significance (Feb 13, 2024)
13-99255079-T-A		not specified	Uncertain significance (Oct 06, 2021)
13-99255182-T-G		not specified	Uncertain significance (Dec 18, 2023)
13-99255217-G-A		not specified	Uncertain significance (Oct 27, 2022)
13-99255224-C-T		not specified	Uncertain significance (Feb 23, 2023)
13-99255245-T-C		not specified	Uncertain significance (Jun 24, 2022)
13-99255314-G-T			Likely benign (Jul 29, 2018)
13-99255430-A-G		not specified	Uncertain significance (Jul 15, 2021)
13-99255446-C-T		not specified	Uncertain significance (Oct 04, 2022)
13-99255452-C-G		not specified	Uncertain significance (Nov 08, 2022)
13-99255542-G-A		not specified	Uncertain significance (Jan 09, 2024)
13-99255655-A-G		not specified	Uncertain significance (Nov 30, 2021)
13-99255657-T-C		not specified	Uncertain significance (Nov 30, 2021)
13-99255712-C-A		not specified	Uncertain significance (Nov 10, 2022)
13-99255769-A-G		not specified	Uncertain significance (Jul 14, 2023)
13-99255796-A-G		not specified	Uncertain significance (May 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPR18	protein_coding	protein_coding	ENST00000340807	1	7031

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.35e-10	0.0337	125712	0	32	125744	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.423	176	193	0.914	0.0000107	2178
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000420	0.000420
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.000294	0.000294
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: GPCRs, Other;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.922
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.25

Haploinsufficiency Scores

• pHI: 0.0708
• hipred: N
• hipred_score: 0.350
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.445

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gpr18
• Phenotype: hematopoietic system phenotype; immune system phenotype; homeostasis/metabolism phenotype

Gene ontology

• 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;positive regulation of Rho protein signal transduction;positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;cytoplasmic vesicle membrane
• Molecular function: G protein-coupled receptor activity