ADGRE3

Summary

ADGRE3 (adhesion G protein-coupled receptor E3, HGNC:23647) is a protein-coding gene on chromosome 19p13.12, encoding Adhesion G protein-coupled receptor E3 (Q9BY15). Orphan receptor that may play a role myeloid-myeloid interactions during immune and inflammatory responses.

This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 2 on chromosome 19. This protein may play a role in myeloid-myeloid interactions during immune and inflammatory responses. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 84658 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_032571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23647
Approved symbol	ADGRE3
Name	adhesion G protein-coupled receptor E3
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131355
Ensembl biotype	protein_coding
OMIM	606101
Entrez	84658

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000253673, ENST00000344373, ENST00000443157, ENST00000595472, ENST00000599900, ENST00000718247, ENST00000961256

RefSeq mRNA: 3 — MANE Select: NM_032571 NM_001289158, NM_001289159, NM_032571

CCDS: CCDS12315, CCDS74296, CCDS74297

Canonical transcript exons

ENST00000253673 — 16 exons

Exon	Start	End
ENSE00001603254	14654982	14655165
ENSE00001648480	14644108	14644275
ENSE00001659550	14658513	14658550
ENSE00001665850	14632921	14633012
ENSE00001682951	14641419	14641616
ENSE00001712570	14638105	14638340
ENSE00001737640	14625492	14625599
ENSE00001743712	14633236	14633302
ENSE00001763527	14630039	14630207
ENSE00001764939	14647181	14647365
ENSE00002246165	14619117	14619471
ENSE00003512108	14651085	14651204
ENSE00003531382	14668802	14668852
ENSE00003573909	14663418	14663540
ENSE00003588901	14661963	14662118
ENSE00004034512	14674746	14674844

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 90.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.2178 / max 1217.4090, expressed in 151 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179673	3.7186	138
179674	0.3853	53
179675	0.1140	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	90.93	gold quality
monocyte	CL:0000576	87.53	gold quality
leukocyte	CL:0000738	87.40	gold quality
mononuclear cell	CL:0000842	87.19	gold quality
granulocyte	CL:0000094	82.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.15	gold quality
vermiform appendix	UBERON:0001154	70.30	gold quality
bone marrow	UBERON:0002371	70.06	gold quality
bone marrow cell	CL:0002092	65.61	gold quality
caecum	UBERON:0001153	65.49	gold quality
periodontal ligament	UBERON:0008266	64.20	gold quality
spleen	UBERON:0002106	63.26	gold quality
right lung	UBERON:0002167	60.96	gold quality
mucosa of urinary bladder	UBERON:0001259	60.10	gold quality
trabecular bone tissue	UBERON:0002483	60.06	gold quality
buccal mucosa cell	CL:0002336	59.86	gold quality
gall bladder	UBERON:0002110	59.54	gold quality
upper lobe of left lung	UBERON:0008952	57.98	gold quality
minor salivary gland	UBERON:0001830	57.17	gold quality
upper lobe of lung	UBERON:0008948	56.80	gold quality
smooth muscle tissue	UBERON:0001135	56.73	gold quality
mouth mucosa	UBERON:0003729	54.96	gold quality
saliva-secreting gland	UBERON:0001044	53.74	gold quality
ileal mucosa	UBERON:0000331	53.58	silver quality
lung	UBERON:0002048	53.48	gold quality
rectum	UBERON:0001052	52.51	gold quality
duodenum	UBERON:0002114	52.01	gold quality
pancreatic ductal cell	CL:0002079	50.05	silver quality
nasal cavity mucosa	UBERON:0001826	49.90	silver quality
epithelial cell of pancreas	CL:0000083	49.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting ADGRE3, 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-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6529-5P	97.85	66.47	673
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-4791	96.51	67.76	659
HSA-MIR-6514-5P	95.07	66.02	655

Literature-anchored findings (GeneRIF, showing 4)

• The expression of EGF-TM7 receptors on myeloid cells is differentially regulated. EMR3 is the first family member found mainly on granulocytes. (PMID:17108056)
• Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased EMR1&3. (PMID:20625511)
• Given the poor survival associated with high levels of EMR-3 expression in glioma patients, impetus is provided to explore EMR-3 as a potential therapeutic target. (PMID:20827226)
• [Peripheral blood EMR3 gene methylation level is correlated with breast cancer in Chinese women]. (PMID:34755660)

Cross-species orthologs

0 orthologs

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), 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), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G protein-coupled receptor E3 — Q9BY15 (reviewed: Q9BY15)

Alternative names: EGF-like module receptor 3, EGF-like module-containing mucin-like hormone receptor-like 3

All UniProt accessions (4): E7EW83, Q9BY15, M0QYN7, M0R1G2

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor that may play a role myeloid-myeloid interactions during immune and inflammatory responses. A ligand for the soluble form of this receptor is present at the surface of monocytes-derived macrophages and activated neutrophils.

Subunit / interactions. Forms a heterodimer, consisting of a large extracellular region (alpha subunit) non-covalently linked to a seven-transmembrane moiety (beta subunit).

Subcellular location. Cell membrane Secreted.

Tissue specificity. Displays a predominantly leukocyte-restricted expression, with highest levels in neutrophils, monocytes and macrophages.

Post-translational modifications. Proteolytically cleaved into 2 subunits, an extracellular alpha subunit and a seven-transmembrane subunit.

Miscellaneous. Has no murine ortholog. Due to a 40-nucleotide deletion (nucleotides 439-479) resulting in a frameshift leading to a premature stop codon and the production of a truncated soluble form.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BY15-1	1	yes
Q9BY15-2	2
Q9BY15-3	3

RefSeq proteins (3): NP_001276087, NP_001276088, NP_115960* (*=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 (45 total): glycosylation site 9, topological domain 8, disulfide bond 8, transmembrane region 7, domain 3, sequence variant 3, region of interest 2, splice variant 2, signal peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY15-F1	80.74	0.31

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 (1): 338–339 (cleavage; by autolysis)

Disulfide bonds (8): 28–37, 31–43, 45–65, 71–85, 79–94, 96–117, 304–333, 321–335

Glycosylation sites (9): 34, 39, 145, 189, 202, 250, 279, 327, 334

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-6798695	Neutrophil degranulation
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 90 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, SHEN_SMARCA2_TARGETS_DN, GOCC_SECRETORY_VESICLE, WU_HBX_TARGETS_2_UP, GOCC_SECRETORY_GRANULE_MEMBRANE, chr19p13, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOCC_TERTIARY_GRANULE, GOCC_FICOLIN_1_RICH_GRANULE, GOCC_FICOLIN_1_RICH_GRANULE_MEMBRANE

GO Biological Process (3): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), 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 (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), secretory granule membrane (GO:0030667), ficolin-1-rich granule membrane (GO:0101003)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
GPCR ligand binding	1
Innate Immune System	1
Immune System	1
Signal Transduction	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
cellular anatomical structure	2
G protein-coupled receptor activity	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
metal ion binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
secretory granule membrane	1
tertiary granule	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRE3	CD55	P08174	821
ADGRE3	EGF	P01133	540
ADGRE3	CCNB1IP1	Q9NPC3	448
ADGRE3	ARL14EP	Q8N8R7	447
ADGRE3	C19orf67	A6NJJ6	418
ADGRE3	CFHR4	Q92496	416
ADGRE3	BPIFA1	Q9NP55	398
ADGRE3	TDRD9	Q8NDG6	394
ADGRE3	ULBP3	Q9BZM4	385
ADGRE3	NTN5	Q8WTR8	383
ADGRE3	C3	P01024	379
ADGRE3	BRME1	Q0VDD7	374
ADGRE3	MAN2B2	Q9Y2E5	374
ADGRE3	DDX25	Q9UHL0	368
ADGRE3	BPIFA2	Q96DR5	366

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A7E2Z9, A8K7I4, B7ZSK1, C6KFA3, P07911, P15396, P17301, P19218, P52787, P53710, Q14CN2, Q16819, Q1WIM2, Q2TU62, Q5T601, Q5VV43, Q5Y4N8, Q61549, Q62469, Q62929, Q66IR0, Q6DJ83, Q6F3F9, Q6PT52, Q6Q473, Q6QMG1, Q6YHK3, Q70VB1, Q862Z3, Q86SQ4, Q8BGZ8, Q8BLQ9, Q8BM96, Q8CJ11, Q8CJ12, Q8IZP9, Q8K4Z6, Q8N3J6, Q8TCW7, Q91X17

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2777 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14600179:GCAC:G	donor_gain	1.0000
19:14600183:G:GG	donor_gain	1.0000
19:14630034:TTTA:T	donor_loss	1.0000
19:14630035:TTAC:T	donor_loss	1.0000
19:14630036:TACC:T	donor_loss	1.0000
19:14630037:ACCTG:A	donor_loss	1.0000
19:14630038:CCTG:C	donor_gain	1.0000
19:14630038:CCTGC:C	donor_loss	1.0000
19:14638337:GCACC:G	acceptor_loss	1.0000
19:14638338:CACCT:C	acceptor_loss	1.0000
19:14638339:ACC:A	acceptor_loss	1.0000
19:14638341:C:A	acceptor_loss	1.0000
19:14638342:T:A	acceptor_loss	1.0000
19:14640704:C:CA	donor_gain	1.0000
19:14641617:C:CA	acceptor_loss	1.0000
19:14641618:T:G	acceptor_loss	1.0000
19:14641624:C:CT	acceptor_gain	1.0000
19:14641624:C:T	acceptor_gain	1.0000
19:14641625:G:T	acceptor_gain	1.0000
19:14644107:CCTGG:C	donor_gain	1.0000
19:14644271:GTCAT:G	acceptor_gain	1.0000
19:14644273:CAT:C	acceptor_gain	1.0000
19:14644275:TCT:T	acceptor_loss	1.0000
19:14644276:C:CC	acceptor_gain	1.0000
19:14644276:CTG:C	acceptor_loss	1.0000
19:14651082:TA:T	donor_loss	1.0000
19:14651200:AATAG:A	acceptor_gain	1.0000
19:14651201:ATAG:A	acceptor_gain	1.0000
19:14651202:TAG:T	acceptor_gain	1.0000
19:14651202:TAGC:T	acceptor_loss	1.0000

AlphaMissense

4288 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14644210:C:A	W316C	0.994
19:14644210:C:G	W316C	0.994
19:14662106:C:G	C71S	0.989
19:14662107:A:T	C71S	0.989
19:14644212:A:G	W316R	0.988
19:14644212:A:T	W316R	0.988
19:14647250:A:C	S271R	0.988
19:14647250:A:T	S271R	0.988
19:14647252:T:G	S271R	0.988
19:14663423:C:G	C65S	0.985
19:14663424:A:T	C65S	0.985
19:14663483:C:G	C45S	0.985
19:14663484:A:T	C45S	0.985
19:14663489:C:G	C43S	0.983
19:14663490:A:T	C43S	0.983
19:14662037:C:G	C94S	0.982
19:14662038:A:T	C94S	0.982
19:14644135:G:C	F341L	0.981
19:14644135:G:T	F341L	0.981
19:14644137:A:G	F341L	0.981
19:14662064:C:G	C85S	0.980
19:14662065:A:T	C85S	0.980
19:14662031:C:G	C96S	0.978
19:14662032:A:T	C96S	0.978
19:14661968:C:G	C117S	0.977
19:14661969:A:T	C117S	0.977
19:14644138:G:C	S340R	0.976
19:14644138:G:T	S340R	0.976
19:14644140:T:G	S340R	0.976
19:14644160:C:G	C333S	0.976

dbSNP variants (sampled 300 via entrez): RS1000024725 (19:14615645 C>T), RS1000043822 (19:14649262 ATC>A), RS1000087526 (19:14609399 A>G), RS1000108708 (19:14655631 AT>A,ATT), RS1000140352 (19:14625316 G>A), RS1000175038 (19:14628478 G>T), RS1000206947 (19:14667605 C>A), RS1000227392 (19:14628184 A>G), RS1000252781 (19:14672264 G>A), RS1000275152 (19:14674258 A>C), RS1000299255 (19:14656877 A>T), RS1000306271 (19:14673910 G>A,C,T), RS1000357545 (19:14621801 T>G), RS1000532207 (19:14611283 A>G), RS1000542829 (19:14609060 A>C)

Disease associations

OMIM: gene MIM:606101 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007059_3	Response to antidepressants (symptom improvement)	5.000000e-06
GCST012490_474	Femur bone mineral density x serum urate levels interaction	9.000000e-10
GCST90000015_10	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0600011	Parkinson’s disease symptom measurement

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

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
PCI 5002	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	decreases expression	1
Calcitriol	increases expression	1
Nickel	decreases expression	1
Tretinoin	increases expression	1
Zinc	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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