ADGRF3

Summary

ADGRF3 (adhesion G protein-coupled receptor F3, HGNC:18989) is a protein-coding gene on chromosome 2p23.3, encoding Adhesion G-protein coupled receptor F3 (Q8IZF5). Orphan receptor.

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to be located in membrane.

Source: NCBI Gene 165082 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 204 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001321971

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18989
Approved symbol	ADGRF3
Name	adhesion G protein-coupled receptor F3
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	hGPCR37, PGR23
Ensembl gene	ENSG00000173567
Ensembl biotype	protein_coding
OMIM	620873
Entrez	165082

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000311519, ENST00000333478, ENST00000421160, ENST00000433584, ENST00000435303, ENST00000447444, ENST00000459892, ENST00000481960, ENST00000487878, ENST00000651242

RefSeq mRNA: 6 — MANE Select: NM_001321971 NM_001145168, NM_001145169, NM_001321971, NM_001321975, NM_001393343, NM_153835

CCDS: CCDS33159, CCDS46238, CCDS46239, CCDS92721

Canonical transcript exons

ENST00000651242 — 14 exons

Exon	Start	End
ENSE00001276981	26314414	26314623
ENSE00003478074	26316275	26316448
ENSE00003588974	26310043	26310105
ENSE00003605175	26313377	26313573
ENSE00003607733	26317496	26317562
ENSE00003609349	26310196	26310237
ENSE00003619067	26313760	26313903
ENSE00003649041	26309526	26309581
ENSE00003659465	26316912	26317055
ENSE00003662683	26310692	26312074
ENSE00003666183	26312943	26313122
ENSE00003843966	26315522	26315740
ENSE00003844669	26308175	26309107
ENSE00003849179	26346121	26346789

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 77.12.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2350 / max 54.2742, expressed in 656 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27419	1.0938	590
27420	0.1412	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.12	gold quality
islet of Langerhans	UBERON:0000006	69.08	gold quality
right testis	UBERON:0004534	68.06	gold quality
left testis	UBERON:0004533	67.45	gold quality
metanephros cortex	UBERON:0010533	66.20	gold quality
bone marrow cell	CL:0002092	65.93	gold quality
ventricular zone	UBERON:0003053	65.83	gold quality
testis	UBERON:0000473	65.53	gold quality
monocyte	CL:0000576	62.50	gold quality
leukocyte	CL:0000738	61.80	gold quality
pancreas	UBERON:0001264	61.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.70	gold quality
adult mammalian kidney	UBERON:0000082	60.60	gold quality
cerebellar cortex	UBERON:0002129	60.31	gold quality
cerebellar hemisphere	UBERON:0002245	60.27	gold quality
right uterine tube	UBERON:0001302	60.10	gold quality
upper leg skin	UBERON:0004262	59.67	silver quality
vermiform appendix	UBERON:0001154	59.35	gold quality
sural nerve	UBERON:0015488	59.32	silver quality
colonic epithelium	UBERON:0000397	59.03	gold quality
cerebellum	UBERON:0002037	59.03	gold quality
lymph node	UBERON:0000029	58.99	gold quality
left ovary	UBERON:0002119	58.79	gold quality
metanephros	UBERON:0000081	58.56	gold quality
cortex of kidney	UBERON:0001225	58.46	gold quality
adenohypophysis	UBERON:0002196	58.45	gold quality
right ovary	UBERON:0002118	58.26	gold quality
calcaneal tendon	UBERON:0003701	57.90	gold quality
spleen	UBERON:0002106	57.76	gold quality
body of pancreas	UBERON:0001150	57.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting ADGRF3, 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-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-499B-5P	98.35	68.39	988

Literature-anchored findings (GeneRIF, showing 1)

• Overexpression of GPR113 is associated with Small bowel primary and metastatic neuroendocrine tumors. (PMID:24114056)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Adgrf3	ENSMUSG00000067642
rattus_norvegicus	Adgrf3	ENSRNOG00000024766

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), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G-protein coupled receptor F3 — Q8IZF5 (reviewed: Q8IZF5)

Alternative names: G-protein coupled receptor 113, G-protein coupled receptor PGR23

All UniProt accessions (4): Q8IZF5, A0A494C083, C9JSE8, F8WE87

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor.

Subunit / interactions. Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked.

Subcellular location. Membrane.

Post-translational modifications. Autoproteolytically processed at the GPS region of the GAIN-B domain; this cleavage modulates receptor activity.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IZF5-1	1	yes
Q8IZF5-2	2
Q8IZF5-3	3

RefSeq proteins (6): NP_001138640, NP_001138641, NP_001308900, NP_001308904, NP_001380272, NP_722577 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR001879	GPCR_2_extracellular_dom	Domain
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR051587	Adhesion_GPCR	Family
IPR056274	Ig_ADGRF3	Domain
IPR057244	GAIN_B	Domain
IPR057400	ADGRF3/5_N	Domain

Pfam: PF00002, PF01825, PF02793, PF24528, PF25387

UniProt features (39 total): topological domain 8, transmembrane region 7, glycosylation site 6, splice variant 5, sequence conflict 5, disulfide bond 2, signal peptide 1, chain 1, domain 1, region of interest 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZF5-F1	74.07	0.29

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): 752–753 (cleavage; by autolysis)

Disulfide bonds (2): 715–747, 734–749

Glycosylation sites (6): 188, 264, 301, 382, 441, 648

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, WTGAAAT_UNKNOWN, AGCYRWTTC_UNKNOWN, GOBP_ADENYLATE_CYCLASE_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, FOSTER_KDM1A_TARGETS_UP, DLX4_TARGET_GENES, FEV_TARGET_GENES, HES4_TARGET_GENES, HOXC6_TARGET_GENES, ID1_TARGET_GENES, ID2_TARGET_GENES

GO Biological Process (4): 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), signal transduction (GO:0007165)

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator 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
signaling receptor activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRF3	ADGRA1	Q86SQ6	573
ADGRF3	CD164L2	Q6UWJ8	502
ADGRF3	OR51T1	Q8NGJ9	463
ADGRF3	OR10H3	O60404	446
ADGRF3	OR1N2	Q8NGR9	435
ADGRF3	OR6N1	Q8NGY5	419
ADGRF3	OR52N5	Q8NH56	419
ADGRF3	MEP1B	Q16820	418
ADGRF3	OR6X1	Q8NH79	400
ADGRF3	OR1L4	Q8NGR5	398
ADGRF3	OR2K2	Q8NGT1	397
ADGRF3	ADGRA3	Q8IWK6	394
ADGRF3	OR52K2	Q8NGK3	369
ADGRF3	ADGRV1	Q8WXG9	364
ADGRF3	ADGRG4	Q8IZF6	354

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ADGRF3	GPR89B	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): GPR113 (Affinity Capture-RNA), GPR113 (Affinity Capture-MS), GPR113 (Affinity Capture-MS), GPR113 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), MAVS (Affinity Capture-MS), GJC1 (Affinity Capture-MS), RAP1A (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), SRC (Affinity Capture-MS), GPR113 (Affinity Capture-MS), GPR113 (Affinity Capture-MS), GPR113 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	168
Likely benign	18
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
60106	GRCh38/hg38 2p23.3(chr2:26332971-26439657)x1	Pathogenic

SpliceAI

2033 predictions. Top by Δscore:

Variant	Effect	Δscore
2:26312937:TCTCA:T	donor_loss	1.0000
2:26312938:CTCAC:C	donor_loss	1.0000
2:26312939:TCA:T	donor_loss	1.0000
2:26312940:CACCT:C	donor_loss	1.0000
2:26312941:A:AT	donor_loss	1.0000
2:26312942:C:CA	donor_loss	1.0000
2:26313758:AC:A	donor_gain	1.0000
2:26313759:CC:C	donor_gain	1.0000
2:26314619:CTCAC:C	acceptor_gain	1.0000
2:26317494:ACC:A	donor_gain	1.0000
2:26317494:ACCC:A	donor_gain	1.0000
2:26317495:CCC:C	donor_gain	1.0000
2:26317495:CCCC:C	donor_gain	1.0000
2:26318964:A:AC	donor_gain	1.0000
2:26318965:C:CC	donor_gain	1.0000
2:26346279:A:AG	donor_gain	1.0000
2:26346279:A:G	donor_gain	1.0000
2:26312085:C:T	acceptor_gain	0.9900
2:26313904:C:CC	acceptor_gain	0.9900
2:26314621:CAC:C	acceptor_gain	0.9900
2:26315085:G:A	donor_gain	0.9900
2:26316445:CACT:C	acceptor_gain	0.9900
2:26317488:ACAC:A	donor_loss	0.9900
2:26317489:CACTC:C	donor_loss	0.9900
2:26317490:ACTCA:A	donor_loss	0.9900
2:26317491:CT:C	donor_loss	0.9900
2:26317492:TCACC:T	donor_loss	0.9900
2:26317493:C:CC	donor_loss	0.9900
2:26317494:AC:A	donor_gain	0.9900
2:26317495:C:G	donor_loss	0.9900

AlphaMissense

6463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:26313437:C:A	W471C	0.994
2:26313437:C:G	W471C	0.994
2:26316390:C:A	W187C	0.990
2:26316390:C:G	W187C	0.990
2:26311463:G:C	F755L	0.988
2:26311463:G:T	F755L	0.988
2:26311465:A:G	F755L	0.988
2:26311541:C:A	W729C	0.988
2:26311541:C:G	W729C	0.988
2:26311574:C:A	W718C	0.988
2:26311574:C:G	W718C	0.988
2:26311577:G:C	F717L	0.988
2:26311577:G:T	F717L	0.988
2:26311579:A:G	F717L	0.988
2:26313456:C:G	C465S	0.984
2:26313457:A:T	C465S	0.984
2:26313530:C:A	W440C	0.981
2:26313530:C:G	W440C	0.981
2:26310713:G:C	F1005L	0.980
2:26310713:G:T	F1005L	0.980
2:26310715:A:G	F1005L	0.980
2:26314604:G:C	F314L	0.976
2:26314604:G:T	F314L	0.976
2:26314606:A:G	F314L	0.976
2:26316392:A:G	W187R	0.976
2:26316392:A:T	W187R	0.976
2:26310996:T:C	Y911C	0.973
2:26314436:C:A	W370C	0.973
2:26314436:C:G	W370C	0.973
2:26316291:G:C	C220W	0.973

dbSNP variants (sampled 300 via entrez): RS1000038941 (2:26326369 G>A), RS1000044547 (2:26331320 C>T), RS1000075620 (2:26331607 G>A), RS1000137158 (2:26340694 A>G), RS1000163151 (2:26333208 A>G,T), RS1000201217 (2:26345974 C>T), RS1000303395 (2:26307724 A>T), RS1000335482 (2:26307918 T>A), RS1000338471 (2:26324261 A>G), RS1000421618 (2:26338951 C>A,T), RS1000444502 (2:26331058 C>A), RS1000529036 (2:26344219 A>C), RS1000538963 (2:26344434 G>A,T), RS1000734785 (2:26324439 C>A), RS1000873007 (2:26336567 A>G)

Disease associations

OMIM: gene MIM:620873 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001734_1	Non-small cell lung cancer	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523891 (SINGLE PROTEIN)

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

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Plant Extracts	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	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
CHEMBL4883397	Binding	PRESTO-Tango GPCRome screening (GPR113)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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