ADGRF5

Summary

ADGRF5 (adhesion G protein-coupled receptor F5, HGNC:19030) is a protein-coding gene on chromosome 6p12.3, encoding Adhesion G protein-coupled receptor F5 (Q8IZF2). Adhesion G protein-coupled receptor.

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; energy reserve metabolic process; and fat cell differentiation. Predicted to act upstream of or within several processes, including glomerular filtration; negative regulation of macrophage activation; and pharyngeal arch artery morphogenesis. Located in cell surface and cytoplasmic vesicle.

Source: NCBI Gene 221395 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 202 total
• Druggable target: yes
• MANE Select transcript: NM_001098518

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19030
Approved symbol	ADGRF5
Name	adhesion G protein-coupled receptor F5
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564O1923, KIAA0758
Ensembl gene	ENSG00000069122
Ensembl biotype	protein_coding
OMIM	620874
Entrez	221395

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 24 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000265417, ENST00000283296, ENST00000478711, ENST00000498632, ENST00000888944, ENST00000888945, ENST00000888946, ENST00000888947, ENST00000888948, ENST00000888949, ENST00000888950, ENST00000888951, ENST00000888952, ENST00000888954, ENST00000888955, ENST00000888957, ENST00000888959, ENST00000888961, ENST00000888963, ENST00000888965, ENST00000888966, ENST00000888967, ENST00000969000, ENST00000969001, ENST00000969002, ENST00000969003

RefSeq mRNA: 2 — MANE Select: NM_001098518 NM_001098518, NM_015234

CCDS: CCDS4919

Canonical transcript exons

ENST00000283296 — 21 exons

Exon	Start	End
ENSE00001426944	46852522	46854071
ENSE00001516393	46921713	46921938
ENSE00003516511	46860715	46860894
ENSE00003581469	46862888	46863096
ENSE00003889003	46855974	46856058
ENSE00003889238	46883559	46883665
ENSE00003889492	46858129	46859523
ENSE00003890059	46888335	46888505
ENSE00003890995	46878202	46878405
ENSE00003891154	46881455	46881597
ENSE00003891170	46865042	46865197
ENSE00003891458	46882049	46882107
ENSE00003891998	46856867	46856908
ENSE00003892948	46868883	46869092
ENSE00003893142	46866925	46867137
ENSE00003894026	46871843	46872013
ENSE00003894171	46906661	46906786
ENSE00003894884	46900029	46900083
ENSE00003894895	46856718	46856777
ENSE00003895173	46884095	46884271
ENSE00003895253	46879818	46880039

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.73.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3883 / max 535.1388, expressed in 392 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73872	3.0028	341
73869	1.6315	266
73870	0.7279	247
73867	0.7054	248
73868	0.1533	100
73866	0.1285	84
73871	0.0297	8
204017	0.0092	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	98.73	gold quality
visceral pleura	UBERON:0002401	98.69	gold quality
right lung	UBERON:0002167	97.96	gold quality
lung	UBERON:0002048	97.52	gold quality
upper lobe of lung	UBERON:0008948	96.96	gold quality
upper lobe of left lung	UBERON:0008952	96.82	gold quality
renal medulla	UBERON:0000362	96.60	gold quality
pleura	UBERON:0000977	96.47	gold quality
heart right ventricle	UBERON:0002080	96.41	gold quality
metanephric glomerulus	UBERON:0004736	96.04	gold quality
vena cava	UBERON:0004087	95.98	gold quality
pericardium	UBERON:0002407	95.74	gold quality
parietal pleura	UBERON:0002400	95.65	gold quality
urethra	UBERON:0000057	95.52	gold quality
renal glomerulus	UBERON:0000074	95.44	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.33	gold quality
omental fat pad	UBERON:0010414	95.28	gold quality
peritoneum	UBERON:0002358	95.26	gold quality
adult mammalian kidney	UBERON:0000082	95.05	gold quality
kidney epithelium	UBERON:0004819	94.99	gold quality
adipose tissue	UBERON:0001013	94.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.59	gold quality
myocardium	UBERON:0002349	94.46	gold quality
kidney	UBERON:0002113	94.25	gold quality
connective tissue	UBERON:0002384	94.14	gold quality
nephron tubule	UBERON:0001231	93.81	gold quality
cortex of kidney	UBERON:0001225	93.78	gold quality
left ventricle myocardium	UBERON:0006566	93.73	gold quality
endothelial cell	CL:0000115	93.40	gold quality
apex of heart	UBERON:0002098	93.29	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	3600.82
E-CURD-119	yes	3448.90
E-CURD-135	yes	1906.14
E-GEOD-83139	yes	722.01
E-HCAD-1	yes	80.75
E-GEOD-134144	yes	38.89
E-HCAD-10	yes	35.25
E-GEOD-135922	yes	32.78
E-MTAB-8410	yes	29.94
E-HCAD-35	yes	20.68
E-GEOD-130148	yes	18.16
E-HCAD-9	yes	17.66
E-CURD-114	yes	10.64
E-MTAB-10137	yes	7.32
E-MTAB-9067	yes	6.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting ADGRF5, 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-3120-5P	100.00	65.56	965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 12)

• SEA domain autoproteolysis accelerated by conformational strain. (PMID:18308334)
• SEA domain autoproteolysis accelerated by conformational strain: mechanistic aspects. (PMID:18314133)
• These findings show that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer. (PMID:24008316)
• our study demonstrated that GPR116 was significantly upregulated in CRC tissues and could serve as an independent prognostic indicator for patients with CRC. (PMID:28624786)
• MiR-511-5p functions as a tumor suppressor and a predictive of prognosis in colorectal cancer by directly targeting GPR116. (PMID:31364112)
• Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype ““Acral FibroChondroMyxoid Tumors””. (PMID:32047233)
• Adhesion-GPCR Gpr116 (ADGRF5) expression inhibits renal acid secretion. (PMID:33004624)
• Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue. (PMID:34016966)
• The Expression Pattern of Adhesion G Protein-Coupled Receptor F5 Is Related to Cell Adhesion and Metastatic Pathways in Colorectal Cancer-Comprehensive Study Based on In Silico Analysis. (PMID:36497132)
• The clinical relevance of the adhesion G protein-coupled receptor F5 for human diseases and cancers. (PMID:36878303)
• The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects. (PMID:38937435)
• GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress. (PMID:39001944)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Adgrf5	ENSMUSG00000056492
rattus_norvegicus	Adgrf5	ENSRNOG00000011154

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), 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), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G protein-coupled receptor F5 — Q8IZF2 (reviewed: Q8IZF2)

Alternative names: G-protein coupled receptor 116

All UniProt accessions (1): Q8IZF2

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion G protein-coupled receptor. In alveolar type II (ATII or AT2) cells, required for normal lung surfactant homeostasis. Modulation of both surfactant secretion and uptake by ATII cells is mediated by the downstream activation of GNAQ/GNA11 proteins and may be a consequence of increased cortical F-actin assembly induced by ADGRF5 activation. In the kidney, may play a role in the regulation of acid excretion into the primary urine, possibly by regulating the surface expression of V-ATPase proton pump. As a receptor for soluble FNDC4 (sFNDC4), required for proper systemic glucose tolerance, specifically sensitizing white adipose tissue to insulin. Also plays a role in sFNDC4-induced decrease of local inflammation in white adipose tissue.

Subunit / interactions. Homodimer; disulfide-linked. 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. Fragment generates by the processing enzyme furin remains attached to the extracellular N-terminal fragment. Interacts (via N-terminal extracellular domain) with SFTPD.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in lung endothelial cells and in alveolar type II (ATII) cells (at protein level). Expressed high levels in subcutaneous adipose tissue in lean individuals and at lower levels in visceral fat. Expression levels in subcutaneous adipose tissue drastically drop in obese individuals.

Post-translational modifications. Highly glycosylated. Proteolytically cleaved at multiple sites: one in the GPS region of the GAIN-B domain (S1 site) and the other in the SEA domain (S2 site). The proteolytic cleavage at S1 site generates an extracellular subunit and a seven-transmembrane subunit. The proteolytic cleavage at S2 site generates a fragment that undergoes proteolytic cleavage by the processing enzyme furin.

Activity regulation. As an adhesion G protein-coupled receptor (aGPCR) exhibits a large N-terminal extracellular domain containing highly conserved GPCR autoproteolysis-inducing (GAIN) domain. During synthesis, intracellular autoproteolytic processing of nascent chain within the GAIN domain generates a mature protein, consisting of an N-terminal fragment that is non-covalently linked to the C-terminal fragment. The mature protein is routed to the plasma membrane where the N- and C-terminal fragments remain associated, forming the holoreceptor. Dissociation of the aGPCR fragments stimulates G protein signaling through the action of the tethered-peptide agonist stalk that is occluded within the GAIN domain in the holoreceptor form. This dissociation might be induced by ligand binding, such as that of sFNDC4.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IZF2-1	1	yes
Q8IZF2-2	2
Q8IZF2-3	3

RefSeq proteins (2): NP_001091988, NP_056049 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008078	GPCR_2_Ig-hepta-like_rcpt	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR051587	Adhesion_GPCR	Family
IPR057244	GAIN_B	Domain
IPR057400	ADGRF3/5_N	Domain

Pfam: PF00002, PF01390, PF01825, PF13927, PF25387

UniProt features (76 total): glycosylation site 21, mutagenesis site 10, topological domain 8, transmembrane region 7, domain 5, disulfide bond 5, region of interest 3, site 3, splice variant 3, sequence variant 3, sequence conflict 3, modified residue 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-Q8IZF2-F1	74.74	0.12

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 (3): 51–52 (cleavage; by furin); 226–227 (cleavage); 990–991 (cleavage; by autolysis)

Post-translational modifications (2): 1300, 1307

Disulfide bonds (5): 293–350, 391–449, 492–545, 954–985, 973–987

Glycosylation sites (21): 73, 94, 106, 188, 256, 272, 301, 315, 328, 398, 472, 487, 505, 540, 627, 649, 666, 820, 931, 963 …

Mutagenesis-validated functional residues (10):

Position	Phenotype
991–996	no effect on activation by exogenous ligands, nor on subcellular location. loss of activation by exogenous ligands; when
1009	no effect on activation by exogenous agonist. increased activation by exogenous agonist; when associated with 991-t–l-9
1075–1077	no effect on activation by exogenous agonist.
1080–1083	no effect on activation by exogenous agonist.
1153	no effect on activation by exogenous agonist; when associated with m-1157 and a-1161.
1157	no effect on activation by exogenous agonist; when associated with q-1153 and a-1161.
1161	no effect on activation by exogenous agonist; when associated with q-1153 and m-1157.
1240–1243	loss of activation by exogenous ligand; when associated with 991-t–l-996 del.
1252	increased activation by exogenous agonists; when associated with 991-t–l-996 del.
1256	increased activation by exogenous agonists; when associated with 991-t–l-996 del.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5683826	Surfactant metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 192 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, TAATAAT_MIR126, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOCC_CELL_SURFACE, GOBP_ARTERY_DEVELOPMENT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (16): glomerular filtration (GO:0003094), 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), phospholipid biosynthetic process (GO:0008654), regulation of lipid metabolic process (GO:0019216), macrophage activation (GO:0042116), glucose homeostasis (GO:0042593), negative regulation of macrophage activation (GO:0043031), surfactant homeostasis (GO:0043129), fat cell differentiation (GO:0045444), erythrocyte development (GO:0048821), pharyngeal arch artery morphogenesis (GO:0061626), positive regulation of phospholipid biosynthetic process (GO:0071073), 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 (5): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
renal filtration	1
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
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
lipid metabolic process	1
regulation of primary metabolic process	1
myeloid leukocyte activation	1
carbohydrate homeostasis	1
negative regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
multicellular organismal-level chemical homeostasis	1
cell differentiation	1
erythrocyte differentiation	1
myeloid cell development	1
artery morphogenesis	1
pharyngeal system development	1
phospholipid biosynthetic process	1
positive regulation of lipid biosynthetic process	1
regulation of phospholipid biosynthetic process	1
positive regulation of phospholipid metabolic process	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

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRF5	FNDC4	Q9H6D8	633
ADGRF5	RAMP2	O60895	581
ADGRF5	ADGRA1	Q86SQ6	542
ADGRF5	ATP10D	Q9P241	418
ADGRF5	ADGRV1	Q8WXG9	400
ADGRF5	ARHGEF25	Q86VW2	394
ADGRF5	ETFBKMT	Q8IXQ9	372
ADGRF5	ADGRG1	Q9Y653	352
ADGRF5	GXYLT2	A0PJZ3	348
ADGRF5	ADGRG3	Q86Y34	331
ADGRF5	GPR107	Q5VW38	328
ADGRF5	OR13C8	Q8NGS7	319
ADGRF5	ADGRA2	Q96PE1	319
ADGRF5	DEFB110	Q30KQ9	317
ADGRF5	RMP64	Q6NW34	315
ADGRF5	TMEM204	Q9BSN7	315

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CABP2	ADGRF5	psi-mi:“MI:0915”(physical association)	0.560
SEC13	ADGRF5	psi-mi:“MI:0915”(physical association)	0.560
NFYC	ADGRF5	psi-mi:“MI:0915”(physical association)	0.560
FNDC3B	ADGRF5	psi-mi:“MI:0915”(physical association)	0.560
ADGRF5	CABP2	psi-mi:“MI:0915”(physical association)	0.560
ADGRF5	RPL13A	psi-mi:“MI:0915”(physical association)	0.400
ADGRF5	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
TREML2	ADGRF5	psi-mi:“MI:0915”(physical association)	0.400
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350
NFYC	ADGRF5	psi-mi:“MI:0915”(physical association)	0.000
FNDC3B	ADGRF5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): GPR116 (Two-hybrid), FNDC3B (Two-hybrid), SEC13 (Two-hybrid), CABP2 (Two-hybrid), GPR116 (Proximity Label-MS), GPR116 (Proximity Label-MS), GPR116 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0M8S8, A3KNS9, B5DFM7, B6ZK76, E9Q9F6, G5E8Q8, O54767, O55006, O73798, P06213, P0DP43, P15127, P15208, P20239, P59823, P59824, P60029, P84329, Q00PJ8, Q07081, Q07E01, Q07E37, Q07E48, Q25410, Q5EG71, Q5SY80, Q6DE92, Q6P7N7, Q6UW88, Q6UX71, Q6X782, Q6X784, Q6X786, Q7YQL9, Q86XM0, Q8BZT5, Q8IZF2, Q8N2E2, Q8SXT3, Q924X1

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	167
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3795 predictions. Top by Δscore:

Variant	Effect	Δscore
6:46856055:TTGA:T	acceptor_gain	1.0000
6:46856056:TGA:T	acceptor_gain	1.0000
6:46856059:C:CC	acceptor_gain	1.0000
6:46879814:CTACC:C	donor_loss	1.0000
6:46879816:A:AC	donor_gain	1.0000
6:46879817:C:CC	donor_gain	1.0000
6:46879817:CCT:C	donor_loss	1.0000
6:46880037:CAT:C	acceptor_gain	1.0000
6:46881448:CACT:C	donor_loss	1.0000
6:46881449:ACTT:A	donor_loss	1.0000
6:46881451:TTA:T	donor_loss	1.0000
6:46881452:TA:T	donor_loss	1.0000
6:46881453:A:AC	donor_gain	1.0000
6:46881453:ACTG:A	donor_loss	1.0000
6:46881454:C:CC	donor_gain	1.0000
6:46881454:CT:C	donor_gain	1.0000
6:46881454:CTG:C	donor_gain	1.0000
6:46881454:CTGA:C	donor_gain	1.0000
6:46881454:CTGAT:C	donor_gain	1.0000
6:46881598:C:CC	acceptor_gain	1.0000
6:46882047:A:AC	donor_gain	1.0000
6:46882048:C:CC	donor_gain	1.0000
6:46882050:TGA:T	donor_gain	1.0000
6:46882108:C:CC	acceptor_gain	1.0000
6:46883558:CCG:C	donor_gain	1.0000
6:46883661:AACAT:A	acceptor_gain	1.0000
6:46883662:ACAT:A	acceptor_gain	1.0000
6:46883663:CAT:C	acceptor_gain	1.0000
6:46883663:CATC:C	acceptor_gain	1.0000
6:46883664:ATCT:A	acceptor_loss	1.0000

AlphaMissense

8918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:46858209:A:G	W1232R	0.998
6:46858209:A:T	W1232R	0.998
6:46858999:C:A	W968C	0.997
6:46858999:C:G	W968C	0.997
6:46856908:C:G	G1259R	0.996
6:46856908:C:T	G1259R	0.996
6:46858345:G:C	N1186K	0.996
6:46858345:G:T	N1186K	0.996
6:46882052:A:G	F223S	0.996
6:46858754:C:G	R1050P	0.995
6:46858825:G:C	S1026R	0.995
6:46858825:G:T	S1026R	0.995
6:46858827:T:G	S1026R	0.995
6:46858150:A:C	F1251L	0.994
6:46858150:A:T	F1251L	0.994
6:46858152:A:G	F1251L	0.994
6:46858924:G:C	F993L	0.994
6:46858924:G:T	F993L	0.994
6:46858926:A:G	F993L	0.994
6:46858985:C:G	C973S	0.994
6:46858986:A:T	C973S	0.994
6:46862948:C:A	W713C	0.994
6:46862948:C:G	W713C	0.994
6:46858232:A:G	L1224P	0.993
6:46858370:G:C	P1178R	0.993
6:46858491:A:G	C1138R	0.993
6:46858596:A:G	W1103R	0.993
6:46858596:A:T	W1103R	0.993
6:46858735:A:C	N1056K	0.993
6:46858735:A:T	N1056K	0.993

dbSNP variants (sampled 300 via entrez): RS1000007775 (6:46857628 C>A), RS1000127317 (6:46935118 C>T), RS1000127794 (6:46872896 C>G,T), RS1000156394 (6:46948652 T>A), RS1000157824 (6:46878658 A>G), RS1000205293 (6:46926096 A>G,T), RS1000309471 (6:46950897 A>C,T), RS1000378491 (6:46921091 A>T), RS1000385735 (6:46922951 G>A), RS1000395147 (6:46867464 C>T), RS1000403749 (6:46878444 A>G), RS1000470671 (6:46883172 C>G,T), RS1000473343 (6:46920895 G>A), RS1000527902 (6:46939602 T>A), RS1000538842 (6:46862117 G>A)

Disease associations

OMIM: gene MIM:620874 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004599_228	Mean platelet volume	3.000000e-10
GCST004625_86	Monocyte count	2.000000e-12
GCST006206_2	Thiopurine-induced alopecia in inflammatory bowel disease	2.000000e-07
GCST006585_1914	Blood protein levels	2.000000e-81
GCST008155_45	Waist-hip ratio	3.000000e-06
GCST90002393_83	Monocyte count	2.000000e-26
GCST90002395_475	Mean platelet volume	2.000000e-20
GCST90002398_373	Neutrophil count	3.000000e-11
GCST90002401_526	Platelet distribution width	4.000000e-17
GCST90002407_265	White blood cell count	2.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0004343	waist-hip ratio
EFO:0004833	neutrophil count
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523888 (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

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
testosterone undecanoate	affects cotreatment, increases expression	1
trichostatin A	decreases expression	1
cobaltous chloride	decreases expression	1
triadimefon	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
clothianidin	decreases expression	1
incobotulinumtoxinA	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Levonorgestrel	affects cotreatment, increases expression	1
Okadaic Acid	decreases 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
CHEMBL4883400	Binding	PRESTO-Tango GPCRome screening (GPR116)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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