MRGPRX3

Summary

MRGPRX3 (MAS related GPR family member X3, HGNC:17980) is a protein-coding gene on chromosome 11p15.1, encoding Mas-related G-protein coupled receptor member X3 (Q96LB0). Orphan receptor.

This gene encodes a member of the mas-related/sensory neuron specific subfamily of G protein coupled receptors. The encoded protein may be involved in sensory neuron regulation and in the modulation of pain.

Source: NCBI Gene 117195 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 95 total
• Druggable target: yes
• MANE Select transcript: NM_001370464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17980
Approved symbol	MRGPRX3
Name	MAS related GPR family member X3
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	MRGX3
Ensembl gene	ENSG00000179826
Ensembl biotype	protein_coding
OMIM	607229
Entrez	117195

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000396275, ENST00000621697

RefSeq mRNA: 2 — MANE Select: NM_001370464 NM_001370464, NM_054031

CCDS: CCDS7830

Canonical transcript exons

ENST00000621697 — 2 exons

Exon	Start	End
ENSE00003742132	18137178	18138488
ENSE00003749219	18132571	18132739

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 56.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3626 / max 34.3212, expressed in 109 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113303	0.3203	100
113302	0.0423	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
minor salivary gland	UBERON:0001830	56.83	gold quality
saliva-secreting gland	UBERON:0001044	55.58	gold quality
mouth mucosa	UBERON:0003729	54.67	gold quality
lower esophagus mucosa	UBERON:0035834	53.64	gold quality
esophagus mucosa	UBERON:0002469	46.89	gold quality
middle temporal gyrus	UBERON:0002771	46.21	gold quality
bone marrow cell	CL:0002092	45.09	gold quality
upper leg skin	UBERON:0004262	44.01	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	43.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
nasal cavity mucosa	UBERON:0001826	42.14	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
colonic epithelium	UBERON:0000397	40.93	gold quality
thoracic mammary gland	UBERON:0005200	40.89	gold quality
mammary gland	UBERON:0001911	40.88	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
sural nerve	UBERON:0015488	40.56	gold quality
stromal cell of endometrium	CL:0002255	40.55	silver 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

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	991.13
E-ENAD-21	yes	770.91
E-ANND-3	no	1.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting MRGPRX3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-1262	98.17	66.52	757

Literature-anchored findings (GeneRIF, showing 4)

• overexpression of the human MrgX3 gene causes a disturbance of the normal cell-differentiation process (PMID:15809047)
• Potential of GPCRs to modulate MAPK and mTOR pathways in different stages of the neurodegenerative disease. (PMID:28189739)
• Our data demonstrate that GPR182 is an endothelial subtype-specific marker for human sinusoidal EC of the liver, spleen, lymph node and bone marrow. In addition, we provide evidence for GPR182-dependent downstream signaling via ERK and SRF pathways that may be involved in regulating endothelial subtype-specific sinusoidal differentiation and sinusoidal functions such as permeability. (PMID:29408502)
• GPCR-mediated EGFR transactivation ameliorates skin toxicities induced by afatinib. (PMID:34552215)

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), MRGPRX1 (ENSG00000170255), MRGPRF (ENSG00000172935), MRGPRD (ENSG00000172938), GPR152 (ENSG00000175514), MRGPRX4 (ENSG00000179817), MRGPRG (ENSG00000182170), MRGPRX2 (ENSG00000183695), MRGPRE (ENSG00000184350), MAS1L (ENSG00000204687)

Protein

Protein identifiers

Mas-related G-protein coupled receptor member X3 — Q96LB0 (reviewed: Q96LB0)

Alternative names: Sensory neuron-specific G-protein coupled receptor 1/2

All UniProt accessions (1): Q96LB0

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain. Potently activated by enkephalins.

Subcellular location. Cell membrane.

Tissue specificity. Uniquely localized in a subset of small dorsal root and trigeminal sensory neurons.

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

RefSeq proteins (2): NP_001357393, NP_473372 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00001

UniProt features (32 total): sequence conflict 14, topological domain 8, transmembrane region 7, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LB0-F1	81.99	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): BILD_HRAS_ONCOGENIC_SIGNATURE, DOUGLAS_BMI1_TARGETS_DN, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MIR148A_3P, MIR152_3P, MIR148B_3P, MIR5700, MIR10523_5P, BLANCO_MELO_COVID19_BRONCHIAL_EPITHELIAL_CELLS_SARS_COV_2_INFECTION_UP, BLANCO_MELO_BRONCHIAL_EPITHELIAL_CELLS_INFLUENZA_A_DEL_NS1_INFECTION_UP, GSE29615_CTRL_VS_DAY3_LAIV_IFLU_VACCINE_PBMC_UP, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY, GSE25088_IL4_VS_IL4_AND_ROSIGLITAZONE_STIM_STAT6_KO_MACROPHAGE_DAY10_DN

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRGPRX3	NPFF	O15130	851
MRGPRX3	TMEM69	Q5SWH9	464
MRGPRX3	TRPA1	O75762	411
MRGPRX3	CCDC137	Q6PK04	407
MRGPRX3	CLRN1	P58418	398
MRGPRX3	ARRB2	P32121	376
MRGPRX3	C1QTNF7	Q9BXJ2	373
MRGPRX3	HTR1D	P28221	373
MRGPRX3	TRPM8	Q7Z2W7	365
MRGPRX3	TAS2R38	P59533	353
MRGPRX3	ZP4	Q12836	353
MRGPRX3	SPICE1	Q8N0Z3	342
MRGPRX3	CYYR1	Q96J86	338
MRGPRX3	MORF4L2	Q15014	336
MRGPRX3	MAB21L4	Q08AI8	331

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TTMP	MRGPRX3	psi-mi:“MI:0915”(physical association)	0.560
RAMP1	MRGPRX3	psi-mi:“MI:0915”(physical association)	0.400
MRGPRX3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
MRGPRX3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	MRGPRX3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	MRGPRX3	psi-mi:“MI:0915”(physical association)	0.400
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
TTMP	MRGPRX3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): MRGPRX3 (Two-hybrid), MRGPRX3 (Affinity Capture-MS)

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: B9VR26, O55197, O88680, P04201, P12526, P23749, P30554, P35410, Q16581, Q2LL16, Q3KNA1, Q3UG50, Q3UG61, Q4QXU0, Q4QXU2, Q4QXU3, Q4QXU4, Q4QXU5, Q4QXU6, Q4QXX9, Q5REI5, Q5U9D9, Q6L786, Q6TAC8, Q6XKD3, Q7TN38, Q7TN39, Q7TN40, Q7TN41, Q7TN44, Q7TN45, Q7TN49, Q7TN50, Q7TN51, Q86SM5, Q8CIP3, Q8NGA4, Q8R4G1, Q8TDS7, Q8VCJ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

676 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18137173:TCCA:T	acceptor_loss	1.0000
11:18137174:CCA:C	acceptor_loss	1.0000
11:18137175:CA:C	acceptor_loss	1.0000
11:18137176:A:AC	acceptor_loss	1.0000
11:18137176:A:AG	acceptor_gain	1.0000
11:18137176:AG:A	acceptor_gain	1.0000
11:18137177:G:GG	acceptor_gain	1.0000
11:18137177:GG:G	acceptor_gain	1.0000
11:18137177:GGGTC:G	acceptor_gain	1.0000
11:18121279:G:GT	donor_gain	0.9900
11:18121279:G:T	donor_gain	0.9900
11:18137176:AGG:A	acceptor_gain	0.9900
11:18137177:GGG:G	acceptor_gain	0.9900
11:18137177:GGGT:G	acceptor_gain	0.9900
11:18121046:G:GT	donor_gain	0.9800
11:18121006:G:GT	donor_gain	0.9700
11:18121092:G:T	donor_gain	0.9700
11:18121242:G:GG	donor_gain	0.9700
11:18121282:G:GG	donor_gain	0.9700
11:18121288:A:T	donor_gain	0.9700
11:18121323:G:T	donor_gain	0.9700
11:18137169:T:TA	acceptor_gain	0.9700
11:18121239:G:GT	donor_gain	0.9600
11:18121239:GAA:G	donor_gain	0.9600
11:18121403:G:T	donor_gain	0.9600
11:18132610:TCAG:T	acceptor_gain	0.9600
11:18132611:CAGC:C	acceptor_gain	0.9600
11:18132613:G:T	acceptor_gain	0.9600
11:18121204:G:T	donor_gain	0.9500
11:18132612:AG:A	acceptor_gain	0.9500

AlphaMissense

2077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18137875:T:C	F225L	0.876
11:18137877:C:A	F225L	0.876
11:18137877:C:G	F225L	0.876
11:18137542:A:C	S114R	0.813
11:18137544:C:A	S114R	0.813
11:18137544:C:G	S114R	0.813
11:18137785:A:C	S195R	0.775
11:18137787:C:A	S195R	0.775
11:18137787:C:G	S195R	0.775
11:18137551:A:C	S117R	0.759
11:18137553:C:A	S117R	0.759
11:18137553:C:G	S117R	0.759
11:18137533:A:C	S111R	0.734
11:18137535:C:A	S111R	0.734
11:18137535:C:G	S111R	0.734
11:18138019:T:C	F273L	0.712
11:18138021:C:A	F273L	0.712
11:18138021:C:G	F273L	0.712
11:18137998:A:C	S266R	0.689
11:18138000:T:A	S266R	0.689
11:18138000:T:G	S266R	0.689
11:18137641:T:A	W147R	0.682
11:18137641:T:C	W147R	0.682
11:18138034:T:C	F278L	0.663
11:18138036:T:A	F278L	0.663
11:18138036:T:G	F278L	0.663
11:18137425:T:C	F75L	0.630
11:18137427:C:A	F75L	0.630
11:18137427:C:G	F75L	0.630
11:18137431:A:C	S77R	0.610

dbSNP variants (sampled 300 via entrez): RS1000034070 (11:18124905 G>A,C), RS1000076297 (11:18135603 G>A,T), RS1000122906 (11:18124360 C>T), RS1000239421 (11:18124172 C>T), RS1000414119 (11:18122019 G>A,C), RS1000636399 (11:18126556 T>A), RS1000678755 (11:18129431 A>T), RS1000705385 (11:18138610 G>A), RS1000899978 (11:18127029 A>G), RS1000901806 (11:18133547 G>A), RS1001257228 (11:18135995 C>G), RS1001326945 (11:18138816 C>T), RS1001449750 (11:18119361 T>TG), RS1001557015 (11:18119640 AG>A), RS1002342018 (11:18119842 C>T)

Disease associations

OMIM: gene MIM:607229 | 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): CHEMBL4523905 (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 no pharmacology

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
terbufos	increases methylation	1
sodium arsenite	increases expression	1
abrine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Parathion	increases methylation	1
Quercetin	increases expression	1
Asbestos, Serpentine	affects expression	1
Asbestos, Crocidolite	affects expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883537	Binding	PRESTO-Tango GPCRome screening (MRGPRX3)	Data for DCP probe UCSF924
CHEMBL5376125	Functional	Agonist activity at MRGPRX3 (unknown origin) by beta-arrestin recruitment assay	Discovery of Potent Agonists for the Predominant Variant of the Orphan MAS-Related G Protein-Coupled Receptor X4 (MRGPRX4). — J Med Chem

Clinical trials (associated diseases)

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