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GPR20

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Target id: 91

Nomenclature: GPR20

Family: Class A Orphans

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 358 8q24.3 GPR20 G protein-coupled receptor 20 3
Mouse 7 358 15 D3 Gpr20 G protein-coupled receptor 20
Rat 6 353 7q34 Gpr20 G protein-coupled receptor 20
Previous and Unofficial Names Click here for help
Gpcr5-1 | P2Y4 | G protein-coupled receptor 5-1
Database Links Click here for help
Specialist databases
GPCRdb gpr20_human (Hs), gpr20_mouse (Mm), o35797_rat (Rn)
Other databases
Alphafold Q99678 (Hs), Q8BYC4 (Mm), O35797 (Rn)
ChEMBL Target CHEMBL4523912 (Hs)
Ensembl Gene ENSG00000204882 (Hs), ENSMUSG00000045281 (Mm), ENSRNOG00000007795 (Rn)
Entrez Gene 2843 (Hs), 239530 (Mm), 60667 (Rn)
Human Protein Atlas ENSG00000204882 (Hs)
KEGG Gene hsa:2843 (Hs), mmu:239530 (Mm), rno:60667 (Rn)
OMIM 601908 (Hs)
Pharos Q99678 (Hs)
RefSeq Nucleotide NM_005293 (Hs), NM_173365 (Mm), NM_022216 (Rn)
RefSeq Protein NP_005284 (Hs), NP_775541 (Mm), NP_071552 (Rn)
UniProtKB Q99678 (Hs), Q8BYC4 (Mm), O35797 (Rn)
Wikipedia GPR20 (Hs)
Antibody Comments
Based on evidence of GPR20's selective expression in gastrointestinal stromal tumours (GISTs), Daiichi Sankyo developed an anti-GPR20 antibody drug conjugate (DS-6157a) to deliver a derivative of the cytotoxic DNA topoisomerase I inhibitor exatecan to tumours [2]. DS-6157a was intended as an alternative to tyrosine kinase inhibitor class GIST therapeutics. Clinical development was discontinued in late 2021, following failure of DS-6157a treatment to demonstrate efficacy in a phase 1 study (NCT04276415) in patients with advanced GIST.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Comments:  GPR20 constitutively activates Gi proteins without ligand stimulation as confirmed by RNA interference and mitogenic response assays [1]
References:  1
Tissue Distribution Click here for help
Brain (thalamus, putamen, caudate), liver
Species:  Human
Technique:  Northern Blot
References:  3
Ubiquitous expression, highest expression small intestine (cell lines: U937, HL60, COLO320)
Species:  Human
Technique:  Real-time PCR
References:  1
Intestine, colon, spleen, testis, ovary (neuroblastoma cell line)
Species:  Mouse
Technique:  Real-time PCR
References:  1
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Disruption of conserved DRY motif by substitution of Asp for Ala at position 148
Species:  Human
Tissue:  HEK-293 cells
Response measured:  Attenuates [35S]GTPγS incorporation and inhibition of prostanglandin E2-induced cAMP production
References:  1
Treatment of cells with pertussis toxin
Species:  Human
Tissue:  HEK-293 cells
Response measured:  Increased basal and prostaglandin E2 induced cAMP production
References:  1
Physiological Functions Comments
Receptor may be involved in intracellular control of cAMP levels and mitogenic signalling [1]
Physiological Consequences of Altering Gene Expression Click here for help
GPR20 overexpression causes increased [35S]GTPγS binding to membrane preparations
Species:  Human
Tissue:  HEK-293 cells
Technique:  Gene over-expression
References:  1
GPR20 deficient mice exhibit hyperactivity disorder characterised by increased total distance travelled in an open field test
Species:  Mouse
Tissue: 
Technique: 
References:  1
GPR20 knockdown causes elevated basal cAMP levels
Species:  Rat
Tissue:  PC12h cells
Technique:  RNAi
References:  1
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  H230R
SNP accession:  rs10875472
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  G313S
Global MAF (%):  5
Subpopulation MAF (%):  AFR|AMR|EUR: 12|7|4
Minor allele count:  T=0.054/119
SNP accession:  VAR_055919, rs34591516
Validation:  1000 Genomes, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  R260C
Global MAF (%):  7
Subpopulation MAF (%):  AFR|AMR|EUR: 26|3|3
Minor allele count:  A=0.075/163
SNP accession:  VAR_055918, rs36092215
Validation:  1000 Genomes, Frequency

References

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1. Hase M, Yokomizo T, Shimizu T, Nakamura M. (2008) Characterization of an orphan G protein-coupled receptor, GPR20, that constitutively activates Gi proteins. J Biol Chem, 283 (19): 12747-55. [PMID:18347022]

2. Iida K, Abdelhamid Ahmed AH, Nagatsuma AK, Shibutani T, Yasuda S, Kitamura M, Hattori C, Abe M, Hasegawa J, Iguchi T et al.. (2021) Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody-Drug Conjugate. Cancer Discov, 11 (6): 1508-1523. [PMID:33579785]

3. O'Dowd BF, Nguyen T, Jung BP, Marchese A, Cheng R, Heng HH, Kolakowski LF, Lynch KR, George SR. (1997) Cloning and chromosomal mapping of four putative novel human G-protein-coupled receptor genes. Gene, 187 (1): 75-81. [PMID:9073069]

Contributors

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