ADGRE1

Summary

ADGRE1 (adhesion G protein-coupled receptor E1, HGNC:3336) is a protein-coding gene on chromosome 19p13.3-p13.2, encoding Adhesion G protein-coupled receptor E1 (Q14246). Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system.

This gene encodes a protein that has a domain resembling seven transmembrane G protein-coupled hormone receptors (7TM receptors) at its C-terminus. The N-terminus of the encoded protein has six EGF-like modules, separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2015 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 165 total — 1 pathogenic
• MANE Select transcript: NM_001974

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3336
Approved symbol	ADGRE1
Name	adhesion G protein-coupled receptor E1
Location	19p13.3-p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174837
Ensembl biotype	protein_coding
OMIM	600493
Entrez	2015

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000250572, ENST00000312053, ENST00000381404, ENST00000381407, ENST00000450315, ENST00000595026, ENST00000596944, ENST00000601198

RefSeq mRNA: 5 — MANE Select: NM_001974 NM_001256252, NM_001256253, NM_001256254, NM_001256255, NM_001974

CCDS: CCDS12175, CCDS58643, CCDS58644, CCDS58645, CCDS58646

Canonical transcript exons

ENST00000312053 — 21 exons

Exon	Start	End
ENSE00001203096	6924678	6924872
ENSE00001203108	6906433	6906521
ENSE00001203117	6937243	6937411
ENSE00001203124	6934987	6935078
ENSE00001203130	6928145	6928211
ENSE00001203136	6926366	6926601
ENSE00001203154	6921713	6921883
ENSE00001203160	6916249	6916368
ENSE00001203168	6908689	6908772
ENSE00001203176	6903810	6903950
ENSE00001203185	6901875	6902021
ENSE00001203197	6904036	6904182
ENSE00001315208	6913653	6913830
ENSE00001319344	6919548	6919747
ENSE00001369614	6890481	6890543
ENSE00001384292	6937544	6937648
ENSE00002312716	6887579	6887639
ENSE00003461925	6896398	6896541
ENSE00003553803	6897428	6897547
ENSE00003587006	6897149	6897304
ENSE00003848724	6940024	6940450

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 92.46.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8111 / max 260.1844, expressed in 278 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173519	3.5673	267
173517	0.1709	90
173518	0.0729	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	92.46	gold quality
mononuclear cell	CL:0000842	92.17	gold quality
leukocyte	CL:0000738	91.94	gold quality
blood	UBERON:0000178	89.09	gold quality
granulocyte	CL:0000094	88.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.00	gold quality
spleen	UBERON:0002106	80.32	gold quality
sperm	CL:0000019	77.62	gold quality
bone marrow	UBERON:0002371	76.81	gold quality
male germ cell	CL:0000015	75.35	gold quality
endometrium epithelium	UBERON:0004811	72.82	gold quality
vermiform appendix	UBERON:0001154	71.83	gold quality
right lung	UBERON:0002167	69.69	gold quality
bone marrow cell	CL:0002092	69.60	gold quality
caecum	UBERON:0001153	67.85	gold quality
palpebral conjunctiva	UBERON:0001812	65.82	silver quality
ileal mucosa	UBERON:0000331	64.00	silver quality
upper lobe of left lung	UBERON:0008952	63.79	gold quality
germinal epithelium of ovary	UBERON:0001304	63.65	gold quality
pancreatic ductal cell	CL:0002079	63.57	silver quality
upper lobe of lung	UBERON:0008948	62.86	gold quality
gall bladder	UBERON:0002110	62.66	gold quality
parietal pleura	UBERON:0002400	62.16	gold quality
lung	UBERON:0002048	61.80	gold quality
lymph node	UBERON:0000029	61.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.37	gold quality
tibialis anterior	UBERON:0001385	60.58	silver quality
paraflocculus	UBERON:0005351	60.10	gold quality
frontal pole	UBERON:0002795	59.58	gold quality
middle frontal gyrus	UBERON:0002702	59.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAF

miRNA regulators (miRDB)

22 targeting ADGRE1, 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-3185	99.99	68.12	1959
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1299	99.77	71.24	2389
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-4729	99.69	72.18	4233
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-6078	75.68	58.05	34

Literature-anchored findings (GeneRIF, showing 5)

• Highly specific marker for eosinophils. (PMID:17823986)
• Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased EMR1&3. (PMID:20625511)
• EMR1 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• The myeloid cell biomarker EMR1 is ectopically expressed in colon cancer. (PMID:34486997)
• Upregulation of EMR1 (ADGRE1) by Tumor-Associated Macrophages Promotes Colon Cancer Progression by Activating the JAK2/STAT1,3 Signaling Pathway in Tumor Cells. (PMID:38673975)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Adgre1	ENSMUSG00000004730
rattus_norvegicus	Adgre1	ENSRNOG00000046254

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G protein-coupled receptor E1 — Q14246 (reviewed: Q14246)

Alternative names: EGF-like module receptor 1, EGF-like module-containing mucin-like hormone receptor-like 1, EMR1 hormone receptor

All UniProt accessions (2): Q14246, M0R2G7

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development.

Subcellular location. Cell membrane.

Tissue specificity. Expression is restricted to eosinophils.

Miscellaneous. Most adhesion GPCRs proteins undergo autoproteolysis at the GPS region of the GAIN-B domain. ADGRE1 is predicted non-cleavable because of the lack of a consensus catalytic triad sequence within GPS region.

Similarity. Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q14246-1	1	yes
Q14246-2	2
Q14246-3	3
Q14246-4	4
Q14246-5	5

RefSeq proteins (5): NP_001243181, NP_001243182, NP_001243183, NP_001243184, NP_001965* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000203	GPS	Conserved_site
IPR000742	EGF	Domain
IPR000832	GPCR_2_secretin-like	Family
IPR001740	GPCR_2_EMR1-like_rcpt	Family
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF01825, PF07645

UniProt features (83 total): disulfide bond 20, sequence variant 14, glycosylation site 12, topological domain 8, transmembrane region 7, domain 7, splice variant 5, sequence conflict 5, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14246-F1	76.75	0.15

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 (20): 35–47, 41–56, 58–78, 84–97, 91–106, 108–130, 136–148, 142–157, 159–170, 176–188, 182–197, 199–219, 225–235, 229–244, 246–266, 272–285, 279–294, 296–315, 550–579, 567–581

Glycosylation sites (12): 94, 99, 127, 167, 189, 194, 232, 258, 312, 366, 375, 448

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 186 (showing top): MODULE_64, GOCC_CELL_SURFACE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, WIELAND_UP_BY_HBV_INFECTION, MODULE_70, GOLDRATH_ANTIGEN_RESPONSE, MODULE_289, RAMALHO_STEMNESS_DN, ROZANOV_MMP14_TARGETS_UP, GOBP_ADAPTIVE_IMMUNE_RESPONSE, RICKMAN_HEAD_AND_NECK_CANCER_A, BRUNO_HEMATOPOIESIS, BRACHAT_RESPONSE_TO_CISPLATIN, HAN_SATB1_TARGETS_DN, WESTON_VEGFA_TARGETS

GO Biological Process (6): adaptive immune response (GO:0002250), cell adhesion (GO:0007155), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), immune system process (GO:0002376), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), calcium ion binding (GO:0005509), transmembrane signaling receptor activity (GO:0004888)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
GPCR ligand binding	1
Signal Transduction	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
signal transduction	2
cellular anatomical structure	2
immune response	1
G protein-coupled receptor activity	1
biological_process	1
cell communication	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
metal ion binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRE1	SCT	P09683	707
ADGRE1	CD55	P08174	631
ADGRE1	CD68	P34810	627
ADGRE1	MRC1	P22897	534
ADGRE1	PTPRC	P08575	524
ADGRE1	CCL2	P13500	522
ADGRE1	TNF	P01375	522
ADGRE1	AIF1	P55008	510
ADGRE1	TREM2	Q9NZC2	504
ADGRE1	LY86	O95711	501
ADGRE1	IL1B	P01584	489
ADGRE1	CTSS	P25774	477
ADGRE1	CD4	P01730	470
ADGRE1	CSF1R	P07333	469
ADGRE1	ITGAM	P11215	453

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ADGRE1	fusA	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A2A259, A5X5Y0, H2Q5A1, O46547, O70212, O95264, O97741, P01906, P01909, P02713, P02715, P02716, P04758, P04759, P04760, P07510, P09660, P09690, P11230, P13536, P18916, P20782, P23979, P25109, P25110, P35563, P37088, P37089, P46098, P55270, P78334, Q04844, Q07001, Q14246, Q5Y4N8, Q60HE8, Q61180, Q61549, Q70Z44, Q7Z418

Diamond homologs: A6QLU6, C0HL12, D4A3T6, E9Q4J9, G5ECX0, G5EDW2, O14514, O35161, O60242, O88278, O88917, O88923, O94910, O95490, O97817, O97827, O97831, P30083, P48960, Q14246, Q2Q421, Q2Q426, Q3UHD1, Q54MC6, Q58Y75, Q59I63, Q5T601, Q5Y4N8, Q61549, Q6F3F9, Q6QNK2, Q7SY09, Q7Z7M1, Q80T32, Q80TR1, Q80TS3, Q80ZF8, Q86SQ3, Q86SQ4, Q8IZF2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	120
Likely benign	12
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2426564	NC_000019.9:g.(?6361586)(8212364_?)del	Pathogenic

SpliceAI

2827 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6887637:GGG:G	donor_gain	1.0000
19:6887638:GGG:G	donor_gain	1.0000
19:6890480:GGAT:G	acceptor_gain	1.0000
19:6896540:AGGTG:A	donor_loss	1.0000
19:6896542:G:T	donor_loss	1.0000
19:6896543:T:G	donor_loss	1.0000
19:6897545:AAG:A	donor_gain	1.0000
19:6897547:GGTAT:G	donor_loss	1.0000
19:6897548:GT:G	donor_loss	1.0000
19:6897549:T:G	donor_loss	1.0000
19:6901866:A:AG	acceptor_gain	1.0000
19:6901873:A:AG	acceptor_gain	1.0000
19:6901874:G:GG	acceptor_gain	1.0000
19:6901874:GAC:G	acceptor_gain	1.0000
19:6902017:TGAAG:T	donor_loss	1.0000
19:6902022:G:GA	donor_loss	1.0000
19:6904183:G:GG	donor_gain	1.0000
19:6906526:G:GG	donor_gain	1.0000
19:6908679:T:A	acceptor_gain	1.0000
19:6908680:G:A	acceptor_gain	1.0000
19:6913651:A:AG	acceptor_gain	1.0000
19:6913652:G:GG	acceptor_gain	1.0000
19:6913688:A:G	acceptor_gain	1.0000
19:6913828:TAG:T	donor_loss	1.0000
19:6913830:GGTA:G	donor_loss	1.0000
19:6916245:TTAG:T	acceptor_loss	1.0000
19:6916246:TAGAC:T	acceptor_loss	1.0000
19:6916247:A:AG	acceptor_gain	1.0000
19:6916248:G:GA	acceptor_gain	1.0000
19:6916248:G:T	acceptor_loss	1.0000

AlphaMissense

5907 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6921778:G:C	W562C	0.986
19:6921778:G:T	W562C	0.986
19:6937361:A:C	S834R	0.984
19:6937363:C:A	S834R	0.984
19:6937363:C:G	S834R	0.984
19:6921776:T:A	W562R	0.983
19:6921776:T:C	W562R	0.983
19:6896535:T:A	C78S	0.982
19:6896536:G:C	C78S	0.982
19:6937292:T:A	W811R	0.982
19:6937292:T:C	W811R	0.982
19:6897244:T:C	F112L	0.980
19:6897246:C:A	F112L	0.980
19:6897246:C:G	F112L	0.980
19:6937346:T:C	F829L	0.978
19:6937348:C:A	F829L	0.978
19:6937348:C:G	F829L	0.978
19:6928182:T:C	F754L	0.977
19:6928184:C:A	F754L	0.977
19:6928184:C:G	F754L	0.977
19:6896487:T:C	F62L	0.975
19:6896489:C:A	F62L	0.975
19:6896489:C:G	F62L	0.975
19:6937370:G:A	G837R	0.975
19:6937370:G:C	G837R	0.975
19:6897160:T:A	C84S	0.972
19:6897161:G:C	C84S	0.972
19:6928151:G:C	W743C	0.972
19:6928151:G:T	W743C	0.972
19:6921751:G:C	W553C	0.971

dbSNP variants (sampled 300 via entrez): RS1000016432 (19:6900686 A>T), RS1000070191 (19:6911471 T>C,G), RS1000072940 (19:6933169 C>T), RS1000182442 (19:6931764 C>T), RS1000200283 (19:6892246 G>A), RS1000322065 (19:6928397 G>A,T), RS1000355228 (19:6922883 C>T), RS1000376703 (19:6926784 A>C), RS1000459487 (19:6915671 T>C), RS1000492631 (19:6900298 G>A,C,T), RS1000615072 (19:6921609 C>A), RS1000718448 (19:6930868 A>C,G), RS1000831678 (19:6890864 C>G), RS1000867623 (19:6904853 C>G), RS1000934031 (19:6927077 A>C,G)

Disease associations

OMIM: gene MIM:600493 | disease phenotypes: MIM:252650

GenCC curated gene-disease

Mondo (1): mucolipidosis type IV (MONDO:0009653)

Orphanet (1): Mucolipidosis type IV (Orphanet:578)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001888_3	Periodontitis	8.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adhesion Class GPCRs

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation	2
Cisplatin	increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
cinnabarinic acid	decreases reaction, increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
tamibarotene	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Erlotinib Hydrochloride	affects cotreatment, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases response to substance	1
Cadmium	decreases expression	1
Copper	affects cotreatment, increases expression	1
Dietary Fats	increases expression, increases reaction	1
N-Nitrosopyrrolidine	increases expression	1
Ozone	affects expression, increases abundance	1
Valproic Acid	decreases methylation	1
Oleic Acid	increases expression, decreases reaction	1
Palmitic Acid	decreases reaction, increases expression	1
Okadaic Acid	increases expression	1
Interleukin 1 Receptor Antagonist Protein	decreases expression, affects cotreatment	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1R8	Abcam HeLa ADGRE1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07398872	PHASE1	ENROLLING_BY_INVITATION	Safety and Efficacy of AAV9. hMCOLN1co For Patients With Mucolipidosis Type IV
NCT00015782	Not specified	COMPLETED	The Natural History and Pathogenesis of Mucolipidosis Type IV
NCT01067742	Not specified	TERMINATED	The Natural History of Mucolipidosis Type IV
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05782387	Not specified	ACTIVE_NOT_RECRUITING	Mucolipidosis Type IV Natural History Study