ADGRF1

Summary

ADGRF1 (adhesion G protein-coupled receptor F1, HGNC:18990) is a protein-coding gene on chromosome 6p12.3, encoding Adhesion G-protein coupled receptor F1 (Q5T601). Adhesion G-protein coupled receptor (aGPCR) for N-docosahexaenoylethanolamine (synaptamide), an omega-3 fatty acid lipid highly enriched in the brain.

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in several processes, including adenylate cyclase-activating G protein-coupled receptor signaling pathway; fat cell differentiation; and nervous system development. Predicted to act upstream of or within memory and positive regulation of CREB transcription factor activity. Predicted to be located in membrane. Predicted to be active in cytoplasmic vesicle and plasma membrane.

Source: NCBI Gene 266977 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 168 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_153840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18990
Approved symbol	ADGRF1
Name	adhesion G protein-coupled receptor F1
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	hGPCR36, PGR19
Ensembl gene	ENSG00000153292
Ensembl biotype	protein_coding
OMIM	617430
Entrez	266977

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000283297, ENST00000371243, ENST00000371253, ENST00000419892, ENST00000449332, ENST00000471487, ENST00000474800, ENST00000475745, ENST00000477771, ENST00000477858, ENST00000487323, ENST00000491283, ENST00000493249, ENST00000890243, ENST00000890244

RefSeq mRNA: 2 — MANE Select: NM_153840 NM_025048, NM_153840

CCDS: CCDS34471, CCDS4920

Canonical transcript exons

ENST00000371253 — 15 exons

Exon	Start	End
ENSE00001454753	46997708	47000295
ENSE00001947349	47042191	47042332
ENSE00003463339	47020731	47020789
ENSE00003507282	47008945	47010318
ENSE00003514333	47005817	47005876
ENSE00003518214	47024044	47024217
ENSE00003527763	47014681	47014844
ENSE00003591678	47012007	47012195
ENSE00003597175	47025854	47026003
ENSE00003598672	47021958	47022058
ENSE00003612242	47016617	47016768
ENSE00003615404	47027704	47027761
ENSE00003660909	47001501	47001567
ENSE00003661983	47007253	47007294
ENSE00003680509	47028993	47029104

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 95.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9632 / max 348.7857, expressed in 154 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73878	1.3762	131
73876	0.4501	105
73877	0.0870	44
73879	0.0168	2
73875	0.0144	6
73874	0.0121	4
73881	0.0038	1
73880	0.0028	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	95.88	gold quality
amniotic fluid	UBERON:0000173	95.42	gold quality
metanephros cortex	UBERON:0010533	93.01	gold quality
lower esophagus mucosa	UBERON:0035834	92.89	gold quality
epithelium of nasopharynx	UBERON:0001951	90.24	gold quality
nasopharynx	UBERON:0001728	90.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.89	gold quality
esophagus mucosa	UBERON:0002469	89.35	gold quality
buccal mucosa cell	CL:0002336	88.40	gold quality
esophagus squamous epithelium	UBERON:0006920	87.97	gold quality
epithelium of esophagus	UBERON:0001976	87.18	gold quality
bronchial epithelial cell	CL:0002328	87.06	gold quality
renal medulla	UBERON:0000362	85.91	gold quality
right lobe of thyroid gland	UBERON:0001119	84.09	gold quality
gall bladder	UBERON:0002110	83.52	gold quality
oral cavity	UBERON:0000167	82.94	gold quality
left lobe of thyroid gland	UBERON:0001120	82.49	gold quality
adult mammalian kidney	UBERON:0000082	82.09	gold quality
epithelium of bronchus	UBERON:0002031	81.94	gold quality
bronchus	UBERON:0002185	81.70	gold quality
thyroid gland	UBERON:0002046	81.23	gold quality
islet of Langerhans	UBERON:0000006	81.09	gold quality
squamous epithelium	UBERON:0006914	79.37	gold quality
urinary bladder	UBERON:0001255	78.25	gold quality
nasal cavity mucosa	UBERON:0001826	77.54	gold quality
nasal cavity epithelium	UBERON:0005384	76.94	gold quality
sperm	CL:0000019	75.72	gold quality
kidney	UBERON:0002113	75.62	gold quality
vagina	UBERON:0000996	75.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.14	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	47.09
E-CURD-119	yes	37.36
E-ANND-3	yes	20.03
E-MTAB-6678	yes	8.51
E-HCAD-30	no	28.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting ADGRF1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-875-3P	99.63	69.47	2548

Literature-anchored findings (GeneRIF, showing 11)

• GPR110 is an oncogene overexpressed in lung and prostate cancer (PMID:20149256)
• GPR56 and GPR110 are activated by exposure of a cryptic tethered agonist (PMID:25918380)
• Study demonstrated orphan G-protein coupled receptor 110 (GPR110, ADGRF1) as the synaptamide receptor, mediating synaptamide-induced bioactivity in a cAMP-dependent manner. (PMID:27759003)
• The results suggested the possible participation of STAT3 instead of ERK in the GPR110 signaling pathways and progression of glioma. (PMID:28728843)
• High GPR110 expression is associated with CRLF2-rearranged acute lymphoblastic leukemia. (PMID:28866095)
• ADGRF1 single-nucleotide polymorphisms role in susceptibility to non-small cell lung cancer (PMID:28968839)
• This signaling pathway leads to the expression of neurogenic and synaptogenic genes and suppresses the expression of proinflammatory genes. The GPR110-dependent cellular effects of synaptamide are recapitulated in animal models, suggesting that synaptamide-derived mechanisms may have translational implications. (PMID:29572109)
• we found that GPR110 knockdown significantly reduced anchorage-dependent/independent cell growth as well as migration/invasion of parental and LTR cells and mammosphere formation in LTR derivatives and not in parental cells. (PMID:29574636)
• Our study revealed that high expression of GPR110 predicts the poor prognosis of gastric cancer patients, and GPTR110 may function as a potential biomarker for the diagnosis of gastric cancer. (PMID:30638950)
• A novel role of ADGRF1 (GPR110) in promoting cellular quiescence and chemoresistance in human epidermal growth factor receptor 2-positive breast cancer. (PMID:34110646)
• GPR110, a receptor for synaptamide, expressed in osteoclasts negatively regulates osteoclastogenesis. (PMID:35690003)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrf11	ENSDARG00000075134
danio_rerio	adgrf7	ENSDARG00000086445
danio_rerio	adgrf6	ENSDARG00000091757
danio_rerio	adgrf8	ENSDARG00000093316
mus_musculus	Adgrf1	ENSMUSG00000041293
rattus_norvegicus	Adgrf1	ENSRNOG00000062544

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), 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 F1 — Q5T601 (reviewed: Q5T601)

Alternative names: G protein-coupled receptor 110, G protein-coupled receptor KPG_012

All UniProt accessions (4): Q5T601, A0A0C4DH10, H7C4N3, H7C570

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion G-protein coupled receptor (aGPCR) for N-docosahexaenoylethanolamine (synaptamide), an omega-3 fatty acid lipid highly enriched in the brain. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. ADGRF1 is coupled to G(s) G proteins and mediates activation of adenylate cyclase activity. Also able to couple to G(q), G(i) and G(12)/G(13) G proteins; additional evidence is however required to confirm this result in vivo. Involved in the development of neurons and cognitive function. In liver, involved in fat accumulation.

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. Cell membrane Secreted.

Tissue specificity. Mainly expressed in the kidney. Up-regulated in lung adenocarcinomas and prostate cancers.

Post-translational modifications. Autoproteolytically processed at the GPS region of the GAIN-B domain; this cleavage modulates receptor activity. Glycosylated. Glycosylation at Asn-389 is required for secretion or folding.

Activity regulation. Forms a heterodimer of 2 chains generated by proteolytic processing that remain associated through non-covalent interactions mediated by the GAIN-B domain. In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation. On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling. The cleaved GAIN-B and N-terminal domains can then dissociate from the rest of the receptor.

Domain organisation. The Stachel sequence (also named stalk) in the C-terminal part of the extracellular domain (ECD) functions as a tethered agonist. In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation. On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T601-1	1	yes
Q5T601-2	2

RefSeq proteins (2): NP_079324, NP_722582* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR008078	GPCR_2_Ig-hepta-like_rcpt	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR051587	Adhesion_GPCR	Family
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF01390, PF01825

UniProt features (152 total): helix 31, mutagenesis site 30, strand 28, glycosylation site 19, topological domain 8, turn 8, transmembrane region 7, disulfide bond 5, sequence conflict 4, chain 3, domain 2, region of interest 2, splice variant 2, signal peptide 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7WY0	ELECTRON MICROSCOPY	2.83
7WZ7	ELECTRON MICROSCOPY	2.83
7WXW	ELECTRON MICROSCOPY	2.84
7WXU	ELECTRON MICROSCOPY	2.85
8HC0	X-RAY DIFFRACTION	2.9
7WU5	ELECTRON MICROSCOPY	3
7X2V	ELECTRON MICROSCOPY	3.09
7WU3	ELECTRON MICROSCOPY	3.1
7WU4	ELECTRON MICROSCOPY	3.4
8G2Y	ELECTRON MICROSCOPY	3.44

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T601-F1	77.05	0.35

Antibody-complex structures (SAbDab): 7 — 7WU3, 7WXU, 7WXW, 7WY0, 7WZ7, 7X2V, 8G2Y

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): 566–567 (cleavage; by autolysis)

Disulfide bonds (5): 257–287, 275–299, 534–561, 549–563, 657–733

Glycosylation sites (19): 139, 168, 205, 282, 310, 317, 329, 354, 368, 389, 410, 423, 437, 455, 512, 528, 553, 736, 739

Mutagenesis-validated functional residues (30):

Position	Phenotype
310	no effect.
389	decreased expression.
565–567	abolished autprocessing, impairing g protein-coupled signaling.
569	strongly decreased g protein-coupled receptor signaling.
570	strongly decreased g protein-coupled receptor signaling.
572	strongly decreased g protein-coupled receptor signaling.
573	strongly decreased g protein-coupled receptor signaling.
589	decreased g protein-coupled receptor signaling.
627	strongly decreased g protein-coupled receptor signaling.
630	strongly decreased g protein-coupled receptor signaling.
672	strongly decreased g protein-coupled receptor signaling.
675	strongly decreased g protein-coupled receptor signaling.
678	strongly decreased g protein-coupled receptor signaling.
681	retains g protein-coupled receptor activity.
682	strongly decreased g protein-coupled receptor signaling.
683	strongly decreased g protein-coupled receptor signaling.
729	decreased g protein-coupled receptor signaling.
755	strongly decreased g protein-coupled receptor signaling.
761	strongly decreased g protein-coupled receptor signaling.
764	strongly decreased g protein-coupled receptor signaling.
765	strongly decreased g protein-coupled receptor signaling.
798	strongly decreased g protein-coupled receptor signaling.
799	strongly decreased g protein-coupled receptor signaling.
800	strongly decreased g protein-coupled receptor signaling.
801	strongly decreased g protein-coupled receptor signaling.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_NEUROGENESIS, FOXO1_01, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELL_JUNCTION_ORGANIZATION, chr6p12, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, HP1SITEFACTOR_Q6, RYTTCCTG_ETS2_B, GOBP_CELL_JUNCTION_ASSEMBLY

GO Biological Process (10): energy reserve metabolic process (GO:0006112), 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), synapse assembly (GO:0007416), memory (GO:0007613), regulation of lipid metabolic process (GO:0019216), neuron projection development (GO:0031175), fat cell differentiation (GO:0045444), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
cellular anatomical structure	2
energy derivation by oxidation of organic compounds	1
G protein-coupled receptor activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
nervous system development	1
cell junction assembly	1
synapse organization	1
learning or memory	1
lipid metabolic process	1
regulation of primary metabolic process	1
neuron development	1
plasma membrane bounded cell projection organization	1
cell differentiation	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
binding	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRF1	ADGRA1	Q86SQ6	584
ADGRF1	ADGRA2	Q96PE1	579
ADGRF1	GPR55	Q9Y2T6	520
ADGRF1	GPR18	Q14330	516
ADGRF1	TRPV1	Q8NER1	463
ADGRF1	TRPM8	Q7Z2W7	425
ADGRF1	FAAH	O00519	422
ADGRF1	GPR119	Q8TDV5	420
ADGRF1	GPR87	Q9BY21	410
ADGRF1	ALDH18A1	P54886	405
ADGRF1	ADGRG5	Q8IZF4	378
ADGRF1	NBPF26	B4DH59	348
ADGRF1	A0A087WTG0	A0A087WTG0	336
ADGRF1	RMP64	Q6NW34	334
ADGRF1	ADGRG4	Q8IZF6	333

IntAct

33 interactions, top by confidence:

A	B	Type	Score
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
GNAS	ADGRF1	psi-mi:“MI:0915”(physical association)	0.400
GNAQ	ADGRF1	psi-mi:“MI:0915”(physical association)	0.400
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ESYT2	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM9B	NBAS	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
UPK2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
P2RX2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASIC4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ITM2C		psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
EPHA7	PLOD2	psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
ECEL1	ADAM10	psi-mi:“MI:0914”(association)	0.350
OR1D4	PROM1	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS), GPR110 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	128
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
149301	GRCh38/hg38 6p21.1-12.1(chr6:45681671-54212044)x1	Pathogenic
146275	GRCh38/hg38 6p21.1-12.3(chr6:44985760-47986838)x3	Likely pathogenic

SpliceAI

2354 predictions. Top by Δscore:

Variant	Effect	Δscore
6:47014748:CA:C	donor_gain	1.0000
6:47014840:CTGGG:C	acceptor_gain	1.0000
6:47016613:TTA:T	donor_loss	1.0000
6:47016614:TA:T	donor_loss	1.0000
6:47016615:ACCT:A	donor_loss	1.0000
6:47016616:C:A	donor_loss	1.0000
6:47016764:CATTT:C	acceptor_gain	1.0000
6:47016765:ATTT:A	acceptor_gain	1.0000
6:47016766:TTT:T	acceptor_gain	1.0000
6:47016767:TT:T	acceptor_gain	1.0000
6:47016767:TTC:T	acceptor_loss	1.0000
6:47016768:TC:T	acceptor_loss	1.0000
6:47016769:C:CC	acceptor_gain	1.0000
6:47016769:CTG:C	acceptor_loss	1.0000
6:47016774:G:C	acceptor_gain	1.0000
6:47016774:G:GC	acceptor_gain	1.0000
6:47016778:T:C	acceptor_gain	1.0000
6:47016778:T:TC	acceptor_gain	1.0000
6:47016780:A:AC	acceptor_gain	1.0000
6:47016780:A:C	acceptor_gain	1.0000
6:47020791:T:C	acceptor_gain	1.0000
6:47020791:T:TC	acceptor_gain	1.0000
6:47021956:A:AC	donor_gain	1.0000
6:47021957:C:CC	donor_gain	1.0000
6:47022059:C:CC	acceptor_gain	1.0000
6:47024042:A:AC	donor_gain	1.0000
6:47024043:C:CC	donor_gain	1.0000
6:47024214:CAGT:C	acceptor_gain	1.0000
6:47024218:C:CC	acceptor_gain	1.0000
6:47042185:GCTTA:G	donor_loss	1.0000

AlphaMissense

5972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:47009803:C:A	W544C	0.995
6:47009803:C:G	W544C	0.995
6:47009805:A:G	W544R	0.990
6:47009805:A:T	W544R	0.990
6:47009638:A:C	S599R	0.982
6:47009638:A:T	S599R	0.982
6:47009640:T:G	S599R	0.982
6:47009728:G:C	F569L	0.982
6:47009728:G:T	F569L	0.982
6:47009730:A:G	F569L	0.982
6:47009789:C:G	C549S	0.982
6:47009790:A:T	C549S	0.982
6:47009824:C:A	W537C	0.982
6:47009824:C:G	W537C	0.982
6:47009827:A:C	F536L	0.977
6:47009827:A:T	F536L	0.977
6:47009829:A:G	F536L	0.977
6:47014748:C:G	C287S	0.977
6:47014749:A:T	C287S	0.977
6:47014732:C:A	W292C	0.976
6:47014732:C:G	W292C	0.976
6:47008966:A:C	F823L	0.975
6:47008966:A:T	F823L	0.975
6:47008968:A:G	F823L	0.975
6:47009025:A:G	W804R	0.971
6:47009025:A:T	W804R	0.971
6:47009834:C:G	C534S	0.971
6:47009835:A:T	C534S	0.971
6:47009992:G:C	S481R	0.967
6:47009992:G:T	S481R	0.967

dbSNP variants (sampled 300 via entrez): RS1000161532 (6:47037787 T>G), RS1000168076 (6:47012438 AT>A), RS1000302832 (6:47009744 G>A,C), RS1000335309 (6:47044086 T>C), RS1000338908 (6:46997626 C>T), RS1000425241 (6:46999895 G>A), RS1000432103 (6:47040960 G>A), RS1000452557 (6:47004429 C>T), RS1000460946 (6:47020637 T>C,G), RS1000773419 (6:47011080 G>A), RS1000797797 (6:47005324 A>G), RS1000801484 (6:47015744 C>T), RS1000816438 (6:47022571 C>T), RS1000830255 (6:47005590 T>G), RS1001030411 (6:46998657 T>A,C)

Disease associations

OMIM: gene MIM:617430 | 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
GCST006206_2	Thiopurine-induced alopecia in inflammatory bowel disease	2.000000e-07
GCST009391_1104	Metabolite levels	8.000000e-06
GCST90002401_527	Platelet distribution width	6.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010447	3-hydroxyanthranilic acid measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523872 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 99,915 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,532

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Adhesion Class GPCRs

ChEMBL bioactivities

11 potent at pChembl≥5 of 11 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.69	EC50	2041	nM	LOPERAMIDE HYDROCHLORIDE
5.69	EC50	2042	nM	CHEMBL484929
5.69	IC50	2051	nM	CHEMBL5092226
5.58	IC50	2599	nM	CHEMBL1256876
5.55	IC50	2839	nM	CHEMBL531742
5.49	IC50	3204	nM	CHEMBL4743495
5.47	IC50	3410	nM	SALMETEROL
5.41	IC50	3894	nM	CHEMBL5089005
5.39	IC50	4064	nM	CHEMBL5075931
5.30	IC50	4997	nM	CHEMBL1474387
5.30	IC50	5042	nM	CHEMBL2018875

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Copper	affects cotreatment, decreases expression, affects binding	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	increases expression, increases abundance	2
ethyl-p-hydroxybenzoate	increases expression	1
quercitrin	decreases expression	1
rofecoxib	affects expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Oils	decreases expression	1
Tetrachlorodibenzodioxin	decreases reaction, increases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression, increases abundance	1
Copper Sulfate	decreases expression	1
S-Nitrosoglutathione	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 5 functional, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883395	Binding	PRESTO-Tango GPCRome screening (GPR110)	Data for DCP probe UCSF924
CHEMBL5209802	Functional	GPCR beta-arrestin recruitment assay with target: ADGRF1 Assay Type: PRESTO-Tango Concentration: 0.00001	GPCR results for EUbOPEN Chemogenomics Library 3

Clinical trials (associated diseases)

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