Nomenclature: MRGPRX4

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 


Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 322 11p15.1 MRGPRX4 MAS-related GPR, member X4
Previous and Unofficial Names
MAS-related GPR, member X4
Sensory neuron-specific G protein-coupled receptor 5/6
Sensory neuron-specific G-protein coupled receptor 5/6
G protein-coupled receptor SNSR5
G protein-coupled receptor SNSR6
G protein-coupled receptor MRGX4
Database Links
Ensembl Gene
Entrez Gene
Human Protein Reference Database
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
UniGene Hs.
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  2
Tissue Distribution
Dorsal root ganglion
Species:  Human
Technique:  RT-PCR
References:  6
Biologically Significant Variants
Type:  Naturally occurring SNPs.
Species:  Human
Description:  S150F, low frequency (<10% in all tested populations)
SNP accession: 
Type:  Naturally occurring SNPs.
Species:  Human
Description:  N25K
SNP accession: 
Type:  SNP
Species:  Human
Change:  F8L
Global MAF (%):  34
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 23|33|48|32
Minor allele count:  G=0.343/750
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  SNP
Species:  Human
Change:  Y54C
Global MAF (%):  38
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 37|34|48|32
Minor allele count:  G=0.377/823
SNP accession: 
Validation:  1000 Genomes, Frequency, Cluster
Type:  SNP
Species:  Human
Change:  L83S
Global MAF (%):  3
Subpopulation MAF (%):  AFR|AMR: 13|1
Minor allele count:  T=0.031/67
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  SNP
Species:  Human
Change:  V142M
Global MAF (%):  3
Subpopulation MAF (%):  AFR|AMR: 12|1
Minor allele count:  A=0.029/64
SNP accession: 
Validation:  1000 Genomes, Frequency, Cluster
Type:  SNP
Species:  Human
Change:  A182V
Global MAF (%):  14
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 6|17|3|27
Minor allele count:  T=0.141/307
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  SNP
Species:  Human
Change:  N245S
Global MAF (%):  2
Subpopulation MAF (%):  AFR|AMR: 10|1
Minor allele count:  G=0.023/51
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
General Comments
MRGPRX4 is a member of the sensory neuron-specific G protein-coupled receptors, which are uniquely expressed in small nociceptive sensory neurons [6].

Of the eight human Mas-related GPCRs (MRGs), four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) have clear orthologues in rodents, whereas the cluster of genes including human MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 is found only in primates and is replaced in rodents with a family of genes (>25 in mice, ~10 in rats) which have no obvious human counterparts [3]. Certain rodent MRGs have been reported to respond to adenine [1] and to RF-amide peptides including neuropeptide FF [4-5] but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch [7-8].
Available Assays
DiscoveRx PathHunter® CHO-K1 MRGPRX4 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0541C2A)
PathHunter® eXpress MRGPRX4 CHO-K1 β-Arrestin Orphan GPCR Assay (Cat no. 93-0541E2ACP1M)
more info


1. Bender E, Buist A, Jurzak M, Langlois X, Baggerman G, Verhasselt P, Ercken M, Guo HQ, Wintmolders C, Van den Wyngaert I et al.. (2002) Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc. Natl. Acad. Sci. U.S.A.99 (13): 8573-8. [PMID:12084918]

2. Burstein ES, Ott TR, Feddock M, Ma JN, Fuhs S, Wong S, Schiffer HH, Brann MR, Nash NR. (2006) Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors. Br. J. Pharmacol.147 (1): 73-82. [PMID:16284629]

3. Dong X, Han S, Zylka MJ, Simon MI, Anderson DJ. (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell106 (5): 619-32. [PMID:11551509]

4. Han SK, Dong X, Hwang JI, Zylka MJ, Anderson DJ, Simon MI. (2002) Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc. Natl. Acad. Sci. U.S.A.99 (23): 14740-5. [PMID:12397184]

5. Lee MG, Dong X, Liu Q, Patel KN, Choi OH, Vonakis B, Undem BJ. (2008) Agonists of the MAS-related gene (Mrgs) orphan receptors as novel mediators of mast cell-sensory nerve interactions. J. Immunol.180 (4): 2251-5. [PMID:18250432]

6. Lembo PM, Grazzini E, Groblewski T, O'Donnell D, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M et al.. (2002) Proenkephalin A gene products activate a new family of sensory neuron--specific GPCRs. Nat. Neurosci.5 (3): 201-9. [PMID:11850634]

7. Liu Q, Tang Z, Surdenikova L, Kim S, Patel KN, Kim A, Ru F, Guan Y, Weng HJ, Geng Y, Undem BJ, Kollarik M, Chen ZF, Anderson DJ, Dong X. (2009) Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell139 (7): 1353-65. [PMID:20004959]

8. Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM. (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat. Neurosci.14 (5): 595-602. [PMID:21460831]

To cite this database page, please use the following:

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: MRGPRX4. Last modified on 09/08/2013. Accessed on 31/10/2014. IUPHAR database (IUPHAR-DB),

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