MRGPRE

Summary

MRGPRE (MAS related GPR family member E, HGNC:30694) is a protein-coding gene on chromosome 11p15.4, encoding Mas-related G-protein coupled receptor member E (Q86SM8). G protein-coupled receptor for L-tryptophanocholate (Trp-CA), an amino-acid-conjugated bile acid produced by the microbiome, which regulates glucose homeostasis.

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 116534 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• MANE Select transcript: NM_001039165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30694
Approved symbol	MRGPRE
Name	MAS related GPR family member E
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	mrgE
Ensembl gene	ENSG00000184350
Ensembl biotype	protein_coding
OMIM	607232
Entrez	116534

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000389832

RefSeq mRNA: 1 — MANE Select: NM_001039165 NM_001039165

CCDS: CCDS41603

Canonical transcript exons

ENST00000389832 — 2 exons

Exon	Start	End
ENSE00001303728	3225030	3228860
ENSE00001562442	3232141	3232417

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 92.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0833 / max 35.6319, expressed in 33 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118288	0.0383	16
118286	0.0217	9
118290	0.0104	2
118289	0.0080	2
118287	0.0049	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	92.12	gold quality
trigeminal ganglion	UBERON:0001675	85.93	gold quality
kidney epithelium	UBERON:0004819	74.97	gold quality
pons	UBERON:0000988	74.46	gold quality
vena cava	UBERON:0004087	66.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	64.17	gold quality
epithelial cell of pancreas	CL:0000083	62.42	gold quality
islet of Langerhans	UBERON:0000006	61.62	gold quality
nasal cavity epithelium	UBERON:0005384	61.44	gold quality
superior vestibular nucleus	UBERON:0007227	61.09	gold quality
substantia nigra pars compacta	UBERON:0001965	60.98	gold quality
quadriceps femoris	UBERON:0001377	60.88	gold quality
vastus lateralis	UBERON:0001379	60.77	gold quality
decidua	UBERON:0002450	59.84	silver quality
medulla oblongata	UBERON:0001896	59.54	gold quality
left ventricle myocardium	UBERON:0006566	59.25	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.86	gold quality
endocervix	UBERON:0000458	58.25	gold quality
pylorus	UBERON:0001166	57.76	gold quality
tibialis anterior	UBERON:0001385	56.90	silver quality
apex of heart	UBERON:0002098	56.80	gold quality
inferior vagus X ganglion	UBERON:0005363	56.54	gold quality
body of tongue	UBERON:0011876	56.54	gold quality
cartilage tissue	UBERON:0002418	56.33	gold quality
hypothalamus	UBERON:0001898	56.29	gold quality
saphenous vein	UBERON:0007318	56.07	gold quality
nipple	UBERON:0002030	56.04	gold quality
mammalian vulva	UBERON:0000997	56.03	silver quality
uterine cervix	UBERON:0000002	55.98	gold quality
pericardium	UBERON:0002407	55.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mrgpre	ENSMUSG00000048965
rattus_norvegicus	Mrgpre	ENSRNOG00000065330

Paralogs (10): MAS1 (ENSG00000130368), MRGPRX1 (ENSG00000170255), MRGPRF (ENSG00000172935), MRGPRD (ENSG00000172938), GPR152 (ENSG00000175514), MRGPRX4 (ENSG00000179817), MRGPRX3 (ENSG00000179826), MRGPRG (ENSG00000182170), MRGPRX2 (ENSG00000183695), MAS1L (ENSG00000204687)

Protein

Protein identifiers

Mas-related G-protein coupled receptor member E — Q86SM8 (reviewed: Q86SM8)

Alternative names: G-protein coupled receptor 167

All UniProt accessions (2): Q86SM8, W4VSQ4

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for L-tryptophanocholate (Trp-CA), an amino-acid-conjugated bile acid produced by the microbiome, which regulates glucose homeostasis. Expressed in enteroendocrine L cells of the gut epithelium: Trp-CA binding causes a conformation change that triggers signaling via G(s) G protein, mediating activation of adenylate cyclase activity. In addition to G(s), MRGPRE also associates with beta-arrestin-1 (ARRB1), promoting phosphorylation of ALDOA. Both G(s) and beta-arrestin-1 signaling pathways improves glucose tolerance by enhancing GLP-1 secretion.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_001034254* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR026230	MRGPCRE	Family
IPR026234	MRGPCRFAMILY	Family

Pfam: PF00001

UniProt features (26 total): topological domain 8, transmembrane region 7, mutagenesis site 7, sequence variant 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SM8-F1	85.21	0.58

Functional residue map

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

Disulfide bonds (1): 162–174

Mutagenesis-validated functional residues (7):

Position	Phenotype
99	decreased g(s)-mediated signaling in response to trp-ca.
103	decreased g(s)-mediated signaling in response to trp-ca. abolished trp-ca-induced glp-1 secretion.
107	decreased g(s)-mediated signaling in response to trp-ca. abolished trp-ca-induced glp-1 secretion.
232	decreased g(s)-mediated signaling in response to trp-ca.
233	decreased g(s)-mediated signaling in response to trp-ca.
251	decreased g(s)-mediated signaling in response to trp-ca.
261	decreased g(s)-mediated signaling in response to trp-ca.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, GOBP_POSITIVE_REGULATION_OF_HORMONE_SECRETION, GOBP_SIGNAL_RELEASE

GO Biological Process (7): intracellular glucose homeostasis (GO:0001678), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway (GO:0038184), signal transduction (GO:0007165)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), G protein-coupled bile acid receptor activity (GO:0038182)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor activity	2
glucose homeostasis	1
intracellular chemical homeostasis	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
cell surface receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
G protein-coupled bile acid receptor activity	1
bile acid signaling pathway	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
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRGPRE	NPFF	O15130	710
MRGPRE	GPR139	Q6DWJ6	481
MRGPRE	GHRH	P01286	468
MRGPRE	MRGPRD	Q8TDS7	452
MRGPRE	STMND1	H3BQB6	418
MRGPRE	ZNF195	O14628	398
MRGPRE	OPN1SW	P03999	365
MRGPRE	MORF4L2	Q15014	358
MRGPRE	GPR149	Q86SP6	316
MRGPRE	SAAL1	Q96ER3	300
MRGPRE	ANKDD1B	A6NHY2	290
MRGPRE	QTGAL	Q67FW5	277
MRGPRE	EFHB	Q8N7U6	276
MRGPRE	CORT	O00230	275
MRGPRE	GPR158	Q5T848	264

IntAct

8 interactions, top by confidence:

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

BioGRID (1): S (Reconstituted Complex)

ESM2 similar proteins: O75388, P04201, P12526, P23749, P30554, P35410, P59536, Q3UG50, Q3UG61, Q5U9D7, Q5Y4Z0, Q645U0, Q645Y3, Q645Z1, Q646B2, Q646C7, Q646E6, Q646F3, Q6L786, Q7TN38, Q7TN39, Q7TN40, Q7TN41, Q7TN44, Q7TN45, Q7TN50, Q7TN51, Q7TQA6, Q86SM5, Q86SM8, Q8CIP3, Q8NGA4, Q8R4G1, Q8TDS7, Q8VCJ6, Q91WW2, Q91WW3, Q91WW4, Q91ZB5, Q91ZB7

Diamond homologs: O55197, P04201, P12526, P23749, P30554, P35410, Q16581, Q2LL16, Q3KNA1, Q3UG50, Q3UG61, Q4QXU0, Q4QXU2, Q4QXU3, Q4QXU4, Q4QXU5, Q4QXU6, Q4QXX9, Q5REI5, Q5U9D7, Q5U9D9, Q6L786, Q6TAC8, Q7TN38, Q7TN39, Q7TN40, Q7TN41, Q7TN44, Q7TN45, Q7TN49, Q7TN50, Q7TN51, Q86SM5, Q86SM8, Q8CIP3, Q8NGA4, Q8R4G1, Q8TDS7, Q8TDT2, Q8VCJ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

229 predictions. Top by Δscore:

Variant	Effect	Δscore
11:3228858:CCC:C	acceptor_gain	1.0000
11:3228859:CC:C	acceptor_gain	1.0000
11:3228859:CCC:C	acceptor_gain	1.0000
11:3228860:CC:C	acceptor_gain	1.0000
11:3228861:C:CC	acceptor_gain	1.0000
11:3228861:CTGTA:C	acceptor_loss	1.0000
11:3228862:T:G	acceptor_loss	1.0000
11:3228856:TGCCC:T	acceptor_gain	0.9900
11:3232136:CTCA:C	donor_loss	0.9900
11:3232137:TCAC:T	donor_loss	0.9900
11:3232138:CACC:C	donor_loss	0.9900
11:3232139:A:AC	donor_gain	0.9900
11:3232139:A:AT	donor_loss	0.9900
11:3232139:AC:A	donor_gain	0.9900
11:3232140:C:CA	donor_loss	0.9900
11:3232140:C:CC	donor_gain	0.9900
11:3232140:CC:C	donor_gain	0.9900
11:3228857:GCCC:G	acceptor_gain	0.9800
11:3228858:CCCC:C	acceptor_gain	0.9800
11:3232140:CCG:C	donor_gain	0.9800
11:3232140:CCGT:C	donor_gain	0.9800
11:3228112:C:CT	acceptor_gain	0.9700
11:3228869:C:CT	acceptor_gain	0.9700
11:3232140:CCGTT:C	donor_gain	0.9700
11:3232170:G:A	donor_gain	0.9700
11:3228869:C:T	acceptor_gain	0.9600
11:3232179:G:T	donor_gain	0.8900
11:3228863:G:GC	acceptor_gain	0.8700
11:3231257:A:C	acceptor_gain	0.8400
11:3231909:A:AC	donor_gain	0.8200

AlphaMissense

1980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:3228038:G:C	S254R	0.987
11:3228038:G:T	S254R	0.987
11:3228040:T:G	S254R	0.987
11:3228584:G:C	F72L	0.979
11:3228584:G:T	F72L	0.979
11:3228586:A:G	F72L	0.979
11:3228484:A:G	C106R	0.975
11:3228464:A:C	S112R	0.974
11:3228464:A:T	S112R	0.974
11:3228466:T:G	S112R	0.974
11:3228580:C:G	G74R	0.973
11:3228212:G:C	S196R	0.969
11:3228212:G:T	S196R	0.969
11:3228214:T:G	S196R	0.969
11:3228577:A:G	C75R	0.966
11:3228358:A:G	W148R	0.959
11:3228358:A:T	W148R	0.959
11:3228488:G:C	F104L	0.958
11:3228488:G:T	F104L	0.958
11:3228490:A:G	F104L	0.958
11:3228674:A:C	N42K	0.958
11:3228674:A:T	N42K	0.958
11:3228122:G:C	F226L	0.956
11:3228122:G:T	F226L	0.956
11:3228124:A:G	F226L	0.956
11:3228349:A:G	C151R	0.955
11:3228506:G:C	S98R	0.953
11:3228506:G:T	S98R	0.953
11:3228508:T:G	S98R	0.953
11:3228672:C:T	G43E	0.953

dbSNP variants (sampled 300 via entrez): RS1000248344 (11:3227964 C>A,T), RS1000908550 (11:3231643 G>A), RS1001054068 (11:3232669 G>A), RS1001402656 (11:3227843 G>A,C,T), RS1001406903 (11:3234028 C>T), RS1001992092 (11:3225530 G>A), RS1002597734 (11:3230250 G>A), RS1002668931 (11:3231175 A>G), RS1003121909 (11:3230428 A>G), RS1003132378 (11:3229718 C>G), RS1003517912 (11:3231084 A>G), RS1003853023 (11:3229406 T>A), RS1003947887 (11:3229656 G>T), RS1005081190 (11:3225992 C>A,T), RS1005181786 (11:3229024 T>C)

Disease associations

OMIM: gene MIM:607232 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001860_1	Multiple sclerosis	2.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523882 (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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tebuconazole	decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Silicon Dioxide	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883532	Binding	PRESTO-Tango GPCRome screening (MRGPRE)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KY46	PathHunter CHO-K1 MRGPRE beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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