MRGPRX1

Summary

MRGPRX1 (MAS related GPR family member X1, HGNC:17962) is a protein-coding gene on chromosome 11p15.1, encoding Mas-related G-protein coupled receptor member X1 (Q96LB2). G protein-coupled receptor specifically expressed in sensory neurons of dorsal root ganglion, and which is involved in itch perception and pain transmission.

Enables transmembrane signaling receptor activity. Involved in cell surface receptor signaling pathway and response to chloroquine. Predicted to be located in cell surface. Predicted to be active in plasma membrane.

Source: NCBI Gene 259249 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 77 total
• Druggable target: yes
• MANE Select transcript: NM_001393578

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17962
Approved symbol	MRGPRX1
Name	MAS related GPR family member X1
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	MRGX1
Ensembl gene	ENSG00000170255
Ensembl biotype	protein_coding
OMIM	607227
Entrez	259249

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000302797, ENST00000526914

RefSeq mRNA: 2 — MANE Select: NM_001393578 NM_001393578, NM_147199

CCDS: CCDS7846

Canonical transcript exons

ENST00000526914 — 2 exons

Exon	Start	End
ENSE00002141941	18933499	18934809
ENSE00002167556	18939280	18939414

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 59.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0711 / max 108.1532, expressed in 6 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118977	0.0568	5
206222	0.0073	2
118978	0.0070	2

Top tissues by expression

230 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.22	gold quality
tendon of biceps brachii	UBERON:0008188	56.09	gold quality
lower lobe of lung	UBERON:0008949	53.82	silver quality
buccal mucosa cell	CL:0002336	50.63	gold quality
upper leg skin	UBERON:0004262	48.62	gold quality
skin of hip	UBERON:0001554	46.20	gold quality
oviduct epithelium	UBERON:0004804	45.70	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

• analysis of the functional interactions between MRGPR-X1 and TRPV1 (PMID:23074220)
• MRGPRX1 is a promising target for pain inhibition, a humanized mouse model expressing this receptor has been described. (PMID:28223516)
• Der p1 also induced the release of IL-6 from heterologous cells expressing MRGPRX1. In summary, activation of Mrgprs by the allergen Der p1 may contribute to inflammation. (PMID:28768771)
• Study reports that a cysteine protease mucunain, active component of cowhage (itch-inducing spicules or trichomes that cover the seedpods of the tropical plant Mucuna pruriens) that is routinely used in human studies of histamine-independent itch, activates human MRGPRX1 and MRGPRX2 receptors and induces degranulation of human mast cells. (PMID:28988117)
• Our findings established a novel function for Mrgprc11 in the gut nociceptive innervation (PMID:31119828)
• BAM8-22 and its receptor MRGPRX1 may attribute to cholestatic pruritus. (PMID:31350433)
• Pruriception and neuronal coding in nociceptor subtypes in human and nonhuman primates. (PMID:33891544)
• Mechanism of agonist-induced activation of the human itch receptor MRGPRX1. (PMID:37347749)
• Ligand recognition and G protein coupling of the human itch receptor MRGPRX1. (PMID:37591889)

Cross-species orthologs

26 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mrgprb2	ENSMUSG00000050425
mus_musculus	Mrgpra1	ENSMUSG00000050650
mus_musculus	Mrgprb8	ENSMUSG00000050870
mus_musculus	Mrgpra6	ENSMUSG00000052303
mus_musculus	Mrgpra4	ENSMUSG00000067173
mus_musculus	Mrgprb3	ENSMUSG00000070546
mus_musculus	Mrgprb1	ENSMUSG00000070547
mus_musculus	Mrgprb4	ENSMUSG00000070550
mus_musculus	Mrgprb5	ENSMUSG00000070551
mus_musculus	Mrgprx1	ENSMUSG00000070552
mus_musculus	Mrgprx2	ENSMUSG00000074109
mus_musculus	Mrgpra9	ENSMUSG00000074111
mus_musculus	Mrgpra3	ENSMUSG00000078698
mus_musculus	Mrgpra2a	ENSMUSG00000093973
mus_musculus	Mrgpra2b	ENSMUSG00000096719
rattus_norvegicus	Mrgprx3	ENSRNOG00000014227
rattus_norvegicus	Mrgprx1	ENSRNOG00000014242
rattus_norvegicus	Mrgprb3l	ENSRNOG00000014266
rattus_norvegicus	Mrgprb5	ENSRNOG00000022703
rattus_norvegicus	Mrgprx2l	ENSRNOG00000022729
rattus_norvegicus	Mrgprb3	ENSRNOG00000028982
rattus_norvegicus	Mrgprb4	ENSRNOG00000033021
rattus_norvegicus	Mrgprb2	ENSRNOG00000037156
rattus_norvegicus	Mrgprb13	ENSRNOG00000074277
rattus_norvegicus		ENSRNOG00000081169
rattus_norvegicus		ENSRNOG00000084911

Paralogs (10): MAS1 (ENSG00000130368), MRGPRF (ENSG00000172935), MRGPRD (ENSG00000172938), GPR152 (ENSG00000175514), MRGPRX4 (ENSG00000179817), MRGPRX3 (ENSG00000179826), MRGPRG (ENSG00000182170), MRGPRX2 (ENSG00000183695), MRGPRE (ENSG00000184350), MAS1L (ENSG00000204687)

Protein

Protein identifiers

Mas-related G-protein coupled receptor member X1 — Q96LB2 (reviewed: Q96LB2)

Alternative names: Sensory neuron-specific G-protein coupled receptor 3/4

All UniProt accessions (3): Q96LB2, A0A494C1K4, W8W3P5

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor specifically expressed in sensory neurons of dorsal root ganglion, and which is involved in itch perception and pain transmission. Specifically activated by a variety of enkephalin (PENK) neuropeptides, such as BAM22 and BAM8-22, which induce itch in a histamine-independent manner. Activated by some tick defensins, such as I.persulcatus Def1 and I.ricinus Def2, evoking itch. Also activated by conotoxin CNF-Tx2, inducing itch sensation. Activated by the antimalarial drug chloroquine; however, activation requires concentrations that exceed the chloroquine concentrations observed in plasma of patients undergoing chloroquine treatment. Also activated following cleavage by the dust mite cysteine protease Der p1. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. MRGPRX1 is both coupled to G(q) and G(i) G proteins: G(q) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, leading to sensitize TRPV1 in pruriceptors, while G(i) coupling mediates inhibition of adenylate cyclase activity. Activation of MRGPRX1 in the peripheral nervous system elicits itch, evoking scratching. MRGPRX1 activation in sensory neurons of the nasal mucosa mediates sneezing responses to irritants or influenza-virus. Activation in the central nervous system dampens chronic pain: BAM8-22-binding at the central terminals prevents pain signals passing to spinal cord neurons, attenuating spinal nociceptive transmission.

Subcellular location. Cell membrane.

Tissue specificity. Specifically expressed in small-diameter sensory neurons of dorsal root ganglion and trigeminal sensory neurons.

Post-translational modifications. Cleavage by D.pteronyssinus cysteine protease Der p1 leads to activation.

Activity regulation. Activated by the positive allosteric modulator ML382 (2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide). Activated by the synthetic small-molecule agonist compound-16 (N-(2-(1-aminoisoquinolin-6-yloxy)-4-methylphenyl)-2-methoxybenzenesulfonamide).

Similarity. Belongs to the G-protein coupled receptor 1 family. Mas subfamily.

RefSeq proteins (3): NP_001380507, NP_001409554, NP_671732 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR026234	MRGPCRFAMILY	Family

Pfam: PF00001

UniProt features (91 total): mutagenesis site 37, helix 13, topological domain 8, transmembrane region 7, sequence variant 7, sequence conflict 6, site 3, strand 3, turn 3, disulfide bond 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8JGF	ELECTRON MICROSCOPY	2.7
8DWG	ELECTRON MICROSCOPY	2.71
8JGB	ELECTRON MICROSCOPY	2.84
8DWC	ELECTRON MICROSCOPY	2.87
8HJ5	ELECTRON MICROSCOPY	3
8JGG	ELECTRON MICROSCOPY	3
8DWH	ELECTRON MICROSCOPY	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LB2-F1	82.85	0.51

Antibody-complex structures (SAbDab): 6 — 8DWC, 8DWG, 8HJ5, 8JGB, 8JGF, 8JGG

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 2–3 (cleavage; by d.pteronyssinus der p 1); 11–12 (cleavage; by d.pteronyssinus der p 1); 22–23 (cleavage; by d.pteronyssinus der p 1)

Disulfide bonds (2): 23–251, 161–173

Glycosylation sites (1): 16

Mutagenesis-validated functional residues (37):

Position	Phenotype
2	does not affect activation by the dust mite cysteine protease der p1.
11	abolished activation by the dust mite cysteine protease der p1.
22	abolished activation by the dust mite cysteine protease der p1.
33	abolished g protein-coupled receptor signaling in response to bam8-22-binding.
59	decreased g(q) g protein-mediated signaling.
61	decreased g(i) g protein-mediated signaling.
82	strongly reduced g protein-coupled receptor signaling in response to bam8-22-binding.
96	strongly reduced g(q) g protein-mediated signaling.
99	strongly reduced activation by the synthetic small-molecule agonist compound-16. strongly reduced activation by conotoxi
106	strongly reduced activation by the synthetic small-molecule agonist compound-16.
119	decreased g(q) g protein-mediated signaling.
124	decreased g(q) g protein-mediated signaling.
130	decreased g(q) g protein-mediated signaling.
131	decreased g(q) g protein-mediated signaling.
132	decreased g(i) g protein-mediated signaling.
134	decreased g(i) g protein-mediated signaling.
157	strongly reduced g protein-coupled receptor signaling in response to cnf-tx2- and bam8-22-binding. strongly reduced acti
160	strongly reduced activation by conotoxin cnf-tx2.
161	abolished g(q) g protein-mediated signaling.
173	abolished g(q) g protein-mediated signaling.
177	abolished g protein-coupled receptor signaling in response to bam8-22-binding. strongly reduced activation by the synthe
198	decreased g(q) g protein-mediated signaling.
213	decreased g(q) g protein-mediated signaling.
214	decreased g(q) g protein-mediated signaling.
217	decreased g(q) g protein-mediated signaling.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_INFLAMMATORY_RESPONSE, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_REFLEX, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_SENSORY_PERCEPTION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION, GOBP_ADENYLATE_CYCLASE_INHIBITING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (10): acute-phase response (GO:0006953), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), sneeze reflex (GO:0160023), sensory perception of itch (GO:0160025), response to chloroquine (GO:1902349), negative regulation of sensory perception of pain (GO:1904057)

GO Molecular Function (2): transmembrane signaling receptor activity (GO:0004888), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor signaling pathway	2
cellular anatomical structure	2
acute inflammatory response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
reflex	1
sensory perception	1
response to nitrogen compound	1
sensory perception of pain	1
negative regulation of nervous system process	1
regulation of sensory perception of pain	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRGPRX1	NPFF	O15130	836
MRGPRX1	GRP	P07491	785
MRGPRX1	AP1B1	P78436	742
MRGPRX1	PENK	P01210	482
MRGPRX1	TRPA1	O75762	468
MRGPRX1	TRPV1	Q8NER1	425
MRGPRX1	CORT	O00230	417
MRGPRX1	MORF4L2	Q15014	370
MRGPRX1	GPR139	Q6DWJ6	368
MRGPRX1	LNP1	A1A4G5	359
MRGPRX1	LPAR3	Q9UBY5	336
MRGPRX1	GNAQ	P50148	317
MRGPRX1	TAC1	P20366	312
MRGPRX1	GPR22	Q99680	310
MRGPRX1	GPR42	O15529	308

IntAct

3 interactions, top by confidence:

A	B	Type	Score
RAMP1	MRGPRX1	psi-mi:“MI:0915”(physical association)	0.400
MRGPRX1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
MRGPRX1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): GNAQ (FRET), GNAI2 (FRET), GNB1 (FRET), GNG2 (FRET)

ESM2 similar proteins: Q2LL16, Q3KNA1, Q3UG50, Q3UG61, Q4QXU0, Q4QXU2, Q4QXU3, Q4QXU4, Q4QXU5, Q4QXU6, Q4QXX9, Q5U9D9, Q645T2, Q645T7, Q645V2, Q645V8, Q645Z2, Q646A2, Q646C4, Q646D6, Q646F4, Q646F6, Q67ES0, Q6L786, Q7TN39, Q7TN41, Q7TN44, Q7TN45, Q7TN49, Q7TN50, Q86SM5, Q8CIP3, Q8R4G1, Q8TDS7, Q91WW2, Q91WW3, Q91WW4, Q91WW5, Q91ZB5, Q91ZB9

Diamond homologs: A4FUQ5, B1PHQ8, B9VR26, E9QJ73, O08726, O08790, O35786, O42179, O70129, O88536, O88634, O88680, O88854, O97571, P0C7U4, P0C7U5, P21109, P21462, P21730, P25024, P25025, P25089, P25090, P30680, P30874, P30875, P30992, P30993, P32299, P32303, P33766, P34993, P34994, P35343, P35344, P35407, P35414, P46090, P46091, P49681

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
MRGPRX1	“up-regulates activity”	GNAS	binding
MRGPRX1	“up-regulates activity”	GNAL	binding
MRGPRX1	“up-regulates activity”	GNAI1	binding
MRGPRX1	“up-regulates activity”	GNAI3	binding
MRGPRX1	“up-regulates activity”	GNAO1	binding
MRGPRX1	“up-regulates activity”	GNAZ	binding
MRGPRX1	“up-regulates activity”	GNAQ	binding
MRGPRX1	“up-regulates activity”	GNA14	binding
QYDAFJUKVGVEKO-PKOVDKIBSA-N	“up-regulates activity”	MRGPRX1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

77 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	19
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

205 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18934532:A:C	donor_gain	1.0000
11:18934888:T:TA	donor_gain	0.9900
11:18934919:A:AC	donor_gain	0.9900
11:18934920:C:CC	donor_gain	0.9900
11:18934938:T:C	donor_gain	0.9900
11:18934685:TCAGC:T	donor_gain	0.9800
11:18934808:CC:C	acceptor_gain	0.9800
11:18934809:CC:C	acceptor_gain	0.9800
11:18934810:C:CC	acceptor_gain	0.9800
11:18934610:T:A	donor_gain	0.9700
11:18934810:C:G	acceptor_loss	0.9700
11:18934530:TA:T	donor_gain	0.9400
11:18934531:AA:A	donor_gain	0.9400
11:18934889:C:A	donor_gain	0.9300
11:18934920:CAG:C	donor_gain	0.9300
11:18934916:CTCA:C	donor_loss	0.9200
11:18934917:TCA:T	donor_loss	0.9200
11:18934918:C:CG	donor_loss	0.9200
11:18934919:ACAG:A	donor_loss	0.9200
11:18934920:CAGAG:C	donor_gain	0.9200
11:18934937:A:AC	donor_gain	0.9200
11:18934531:A:AC	donor_gain	0.9100
11:18934805:TGACC:T	acceptor_gain	0.9100
11:18934806:GACC:G	acceptor_gain	0.9100
11:18934914:GAC:G	donor_loss	0.9100
11:18934807:ACC:A	acceptor_gain	0.9000
11:18934808:CCC:C	acceptor_gain	0.9000
11:18934810:C:T	acceptor_gain	0.9000
11:18934920:CA:C	donor_gain	0.9000
11:18934920:CAGA:C	donor_gain	0.9000

AlphaMissense

1363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18934443:A:C	S114R	0.944
11:18934443:A:T	S114R	0.944
11:18934445:T:G	S114R	0.944
11:18934434:G:C	S117R	0.935
11:18934434:G:T	S117R	0.935
11:18934436:T:G	S117R	0.935
11:18934200:G:C	S195R	0.927
11:18934200:G:T	S195R	0.927
11:18934202:T:G	S195R	0.927
11:18934452:G:C	S111R	0.904
11:18934452:G:T	S111R	0.904
11:18934454:T:G	S111R	0.904
11:18934346:A:G	W147R	0.865
11:18934346:A:T	W147R	0.865
11:18934584:G:C	N67K	0.851
11:18934584:G:T	N67K	0.851
11:18934650:G:C	N45K	0.845
11:18934650:G:T	N45K	0.845
11:18934602:G:C	F61L	0.835
11:18934602:G:T	F61L	0.835
11:18934604:A:G	F61L	0.835
11:18934560:G:C	F75L	0.826
11:18934560:G:T	F75L	0.826
11:18934562:A:G	F75L	0.826
11:18934358:A:G	C143R	0.817
11:18934569:G:C	D72E	0.815
11:18934569:G:T	D72E	0.815
11:18934664:C:G	G41R	0.815
11:18934664:C:T	G41R	0.815
11:18934554:G:C	S77R	0.810

dbSNP variants (sampled 300 via entrez): RS1000000303 (11:18938457 A>C), RS1000286628 (11:18936545 G>A,T), RS1000605735 (11:18934657 G>A,C), RS1001123347 (11:18939314 C>T), RS1001573347 (11:18936028 T>G), RS1001604406 (11:18935689 G>A), RS1002008739 (11:18940521 C>A), RS1002526627 (11:18940333 G>T), RS1002616746 (11:18936980 G>C), RS1003505118 (11:18938152 A>G), RS1003731046 (11:18933456 T>C,G), RS1003763764 (11:18933165 A>G), RS1004241943 (11:18938837 C>T), RS1004512967 (11:18936721 C>G,T), RS1005822251 (11:18937910 A>G)

Disease associations

OMIM: gene MIM:607227 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5850 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class A Orphans with emerging pharmacology

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
bovine adrenal medulla peptide 8-22	Full agonist	7.68	pKi
compound 16 [PMID: 31498617]	Agonist	7.3	pEC50
GPR15L	Agonist	4.74	pEC50
chloroquine	Agonist	3.53	pEC50

ChEMBL bioactivities

158 potent at pChembl≥5 of 168 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.20	EC50	6.31	nM	CHEMBL475965
7.89	EC50	13	nM	CHEMBL5195160
7.85	EC50	14	nM	CHEMBL5172913
7.85	IC50	14	nM	CHEMBL1762707
7.70	EC50	19.95	nM	CHEMBL477008
7.70	IC50	20	nM	CHEMBL1762698
7.66	IC50	22	nM	CHEMBL1762699
7.62	EC50	23.99	nM	CHEMBL474473
7.62	IC50	24	nM	CHEMBL1762700
7.60	EC50	25.12	nM	CHEMBL475965
7.60	EC50	25.12	nM	CHEMBL3716029
7.51	EC50	31	nM	CHEMBL5205606
7.40	IC50	40	nM	CHEMBL1762701
7.30	EC50	50.12	nM	CHEMBL3343989
7.30	IC50	50	nM	CHEMBL1762707
7.30	IC50	50	nM	CHEMBL3343995
7.30	EC50	50	nM	CHEMBL3343989
7.30	EC50	50	nM	CHEMBL4460098
7.28	EC50	52.48	nM	CHEMBL474474
7.27	EC50	54	nM	CHEMBL5202767
7.26	EC50	55	nM	CHEMBL5185447
7.20	EC50	63.1	nM	CHEMBL502132
7.19	IC50	64	nM	CHEMBL3727438
7.16	EC50	69	nM	CHEMBL5194692
7.11	IC50	77	nM	CHEMBL1760000
7.10	IC50	80	nM	CHEMBL3730717
7.10	EC50	80	nM	CHEMBL5177145
7.09	EC50	81.28	nM	CHEMBL475077
7.06	IC50	88	nM	CHEMBL1762702
7.05	IC50	90	nM	CHEMBL3730500
7.01	EC50	98	nM	CHEMBL5171656
7.00	EC50	100	nM	CHEMBL4565294
7.00	EC50	100	nM	CHEMBL5084093
6.99	EC50	103	nM	CHEMBL5200001
6.97	EC50	107.2	nM	CHEMBL448975
6.97	IC50	108	nM	CHEMBL1762705
6.91	IC50	124	nM	CHEMBL3730405
6.91	EC50	124	nM	CHEMBL5177388
6.91	EC50	123	nM	CHEMBL475282
6.90	EC50	125.9	nM	CHEMBL458220
6.88	EC50	131.8	nM	CHEMBL449189
6.85	IC50	140	nM	CHEMBL3730599
6.84	EC50	144.5	nM	CHEMBL477432
6.82	EC50	150	nM	CHEMBL4455263
6.80	EC50	158.5	nM	CHEMBL3717681
6.80	EC50	160	nM	CHEMBL4541091
6.79	IC50	163	nM	CHEMBL3731811
6.78	IC50	165	nM	CHEMBL3727861
6.76	EC50	173	nM	CHEMBL5208855
6.74	IC50	182	nM	CHEMBL3730717

PubChem BioAssay actives

116 with measured affinity, of 308 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-(6-methoxy-3-pyridinyl)-N-[2-methyl-3-[(6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]phenyl]benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0063	uM
2-(cyclopropylsulfonylamino)-N-(2-ethoxy-5-fluorophenyl)-5-fluorobenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0130	uM
2-(cyclopropylsulfonylamino)-N-(2-ethoxy-5-fluorophenyl)benzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0140	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-[(3,5-dichloro-4-pyridinyl)methyl]-N-(3-morpholin-4-ylpropyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0140	uM
N-[2-methyl-3-[(6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]phenyl]-4-phenylbenzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0199	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-(furan-2-ylmethyl)-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0200	uM
N-benzyl-2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0220	uM
N-[3-[(5-chloro-6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]-2-methylphenyl]-4-(6-methoxy-3-pyridinyl)benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0240	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-[(3,5-dichloro-4-pyridinyl)methyl]-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0240	uM
N-(2-ethoxy-5-fluorophenyl)-2-(ethylsulfonylamino)-5-fluorobenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0310	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-(oxolan-2-ylmethyl)-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0400	uM
N-[2-(1-aminoisoquinolin-6-yl)oxy-4-methylphenyl]-2-methoxybenzenesulfonamide	1540483: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay	ec50	0.0500	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-6-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-(carboxymethylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-1-[(2S)-2-[[2-[[(2S)-2-amino-3-methylbutanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid	1540477: Agonist activity at human MrgprX1	ec50	0.0500	uM
3-[4-[[3-[(5-chloro-6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]-2-methylphenyl]carbamoyl]phenyl]benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0525	uM
5-chloro-2-(cyclopropylsulfonylamino)-N-(2-ethoxyphenyl)benzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0540	uM
5-chloro-2-(cyclopropylsulfonylamino)-N-(2-ethoxy-5-fluorophenyl)benzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0550	uM
(7S)-7-butan-2-yl-2-[3-(dimethylamino)propylamino]-6-oxo-N-[[3-(trifluoromethyl)phenyl]methyl]-5,7-dihydrobenzimidazolo[1,2-d][1,4]benzodiazepine-11-carboxamide	414289: Agonist activity at human MrgX1 receptor	ec50	0.0631	uM
2-(cyclopropylsulfonylamino)-N-(2-ethoxy-5-fluorophenyl)-5-methylbenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0690	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-[(3,5-dichloro-4-pyridinyl)methyl]-N-ethylacetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0770	uM
N-(2-ethoxy-5-fluorophenyl)-2-(ethylsulfonylamino)-5-methylbenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0800	uM
N-[3-[[5-chloro-4-(1,4-diazepan-1-yl)-6-oxopyridazin-1-yl]methyl]-2-methylphenyl]-4-(6-methoxy-3-pyridinyl)benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.0813	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-(3-methoxypropyl)-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.0880	uM
N-(2-ethoxyphenyl)-2-(ethylsulfonylamino)-5-fluorobenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.0980	uM
4-[2-[(2-methoxyphenyl)sulfonylamino]-5-methylphenoxy]benzenecarboximidamide	1540483: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay	ec50	0.1000	uM
6-tert-butyl-5-(3,4-dichlorophenyl)-4-[2-(trifluoromethoxy)phenoxy]thieno[2,3-d]pyrimidine	1819424: Positive allosteric modulator activity at human MRGPRX1 transfected in HEK293 cells in presence of BAM8-22 by Fulo4AM dye based FLIPR assay	ec50	0.1000	uM
2-(cyclopropylsulfonylamino)-N-(2-ethoxyphenyl)-5-methylbenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.1030	uM
N-[3-[[5-chloro-4-[(1S,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-6-oxopyridazin-1-yl]methyl]-2-methylphenyl]-4-(6-methoxy-3-pyridinyl)benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.1071	uM
N-[(3-bromo-4-pyridinyl)methyl]-2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-ethylacetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.1080	uM
N-[3-[[5-chloro-4-(4-methylpiperazin-1-yl)-6-oxopyridazin-1-yl]methyl]-2-methylphenyl]-4-(6-methoxy-3-pyridinyl)benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.1230	uM
2-(cyclopropylsulfonylamino)-N-(2-ethoxyphenyl)benzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.1240	uM
N-[3-[(5-chloro-6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]-2-methylphenyl]-4-phenylbenzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.1259	uM
N-[3-[(5-chloro-6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]-2-methylphenyl]-4-quinolin-6-ylbenzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.1318	uM
N-[3-[(5-chloro-6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]-2-methylphenyl]-4-thiophen-3-ylbenzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.1445	uM
4-[5-methyl-2-[[2-(trifluoromethoxy)phenyl]sulfonylamino]phenoxy]benzenecarboximidamide	1540483: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay	ec50	0.1500	uM
4-[5-methyl-2-[(4-methylphenyl)sulfonylamino]phenoxy]benzenecarboximidamide	1540483: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay	ec50	0.1600	uM
2-(cyclopropylsulfonylamino)-N-(2-ethoxyphenyl)-5-fluorobenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.1730	uM
(7S)-7-butan-2-yl-6-oxo-2-(2-piperidin-1-ylethylamino)-N-[[3-(trifluoromethyl)phenyl]methyl]-5,7-dihydrobenzimidazolo[1,2-d][1,4]benzodiazepine-11-carboxamide	414289: Agonist activity at human MrgX1 receptor	ec50	0.1995	uM
5-chloro-N-(2-ethoxy-5-fluorophenyl)-2-(ethylsulfonylamino)benzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.2060	uM
N-(2-ethoxyphenyl)-2-(ethylsulfonylamino)-5-methylbenzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.2170	uM
4-(2-fluorophenoxy)-5,6-dimethylthieno[2,3-d]pyrimidine	1819424: Positive allosteric modulator activity at human MRGPRX1 transfected in HEK293 cells in presence of BAM8-22 by Fulo4AM dye based FLIPR assay	ec50	0.2200	uM
6-tert-butyl-5-(4-fluorophenyl)-4-[2-(trifluoromethoxy)phenoxy]thieno[2,3-d]pyrimidine	1819424: Positive allosteric modulator activity at human MRGPRX1 transfected in HEK293 cells in presence of BAM8-22 by Fulo4AM dye based FLIPR assay	ec50	0.2300	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-ethyl-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.2440	uM
N-(2-ethoxy-5-fluorophenyl)-2-(ethylsulfonylamino)benzamide	1910835: Positive allosteric modulator activity at human MRGPRX1 expressed in HEK293 cells in presence of BAM8-22 by Fluo4-dye based FLIPR assay	ec50	0.2850	uM
N-[3-[(5-chloro-6-oxo-4-piperazin-1-ylpyridazin-1-yl)methyl]-2-methylphenyl]-4-quinolin-8-ylbenzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.2884	uM
4-[[3-methoxy-4-(thiophen-3-ylmethoxy)phenyl]methylamino]benzenecarboximidamide	1540483: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay	ec50	0.2900	uM
2-[4-[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]piperazin-1-yl]-N-(cyclopropylmethyl)-N-(pyridin-4-ylmethyl)acetamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.2950	uM
N-[3-[[5-chloro-4-[2-(methylamino)ethylamino]-6-oxopyridazin-1-yl]methyl]-2-methylphenyl]-4-(6-methoxy-3-pyridinyl)benzamide	368592: Agonist activity at human MrgX1 receptor expressed in HEK293 cells assessed as intracellular calcium mobilization by FLIPR assay	ec50	0.2951	uM
4-[2-(butylsulfonylamino)phenoxy]benzenecarboximidamide	1540483: Agonist activity at human MrgprX1 expressed in HEK293 cells incubated for 2 mins by Fluo4AM dye based FLIPR assay	ec50	0.3000	uM
6-tert-butyl-4-(2-fluorophenoxy)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine	1819424: Positive allosteric modulator activity at human MRGPRX1 transfected in HEK293 cells in presence of BAM8-22 by Fulo4AM dye based FLIPR assay	ec50	0.3000	uM
4-[2-[[2-[2-(4-chlorophenyl)ethylamino]pyrimidin-4-yl]amino]ethyl]benzenesulfonamide	590493: Antagonist activity at SNSR4 in human HEK293 cells by FLIPR assay	ic50	0.3010	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Endosulfan	increases expression	2
ethyl-p-hydroxybenzoate	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

33 unique, capped per target: 20 binding, 12 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015292	Functional	Agonist activity at human MrgX1 receptor	Discovery of non-peptidergic MrgX1 and MrgX2 receptor agonists and exploration of an initial SAR using solid-phase synthesis. — Bioorg Med Chem Lett
CHEMBL3388384	Binding	Agonist activity at human MrgX1 transfected in HEK293 cells by FLIPR assay	Peptidomimetics of Arg-Phe-NH2 as small molecule agonists of Mas-related gene C (MrgC) receptors. — Bioorg Med Chem
CHEMBL4673571	ADMET	Activation of human MrgprX1 expressed in BAM 8-22 activated-rat KNRK cells by fura2-AM dye based calcium imaging assay	Hormone-like conopeptides - new tools for pharmaceutical design — RSC Med Chem

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E5JS	CHO-K1/Galpha15/MRGPRX1	Spontaneously immortalized cell line	Female
CVCL_KU65	RBL-2H3 MRGPRX1 Gq	Cancer cell line
CVCL_KY48	PathHunter CHO-K1 MRGPRX1 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.