OXGR1

Summary

OXGR1 (oxoglutarate receptor 1, HGNC:4531) is a protein-coding gene on chromosome 13q32.1, encoding 2-oxoglutarate receptor 1 (Q96P68). G protein-coupled receptor for dicarboxylates and amino dicarboxylates.

This gene encodes a G protein-coupled receptor (GPCR) that belongs to the oxoglutarate receptor family within the GPCR superfamily. The encoded protein is activated by the citric acid intermediate, oxoglutarate, as well as several cysteinyl leukotrienes, including leukotrienes E4, C4 and D4, which are implicated in many inflammatory disorders. In mice, a knock-out of this gene leads to middle ear inflammation, changes in the mucosal epithelium, and an increase in fluid behind the eardrum, and is associated with hearing loss. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 27199 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 69 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_001346194

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4531
Approved symbol	OXGR1
Name	oxoglutarate receptor 1
Location	13q32.1
Locus type	gene with protein product
Status	Approved
Aliases	P2RY15, P2Y15, aKGR
Ensembl gene	ENSG00000165621
Ensembl biotype	protein_coding
OMIM	606922
Entrez	27199

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000298440, ENST00000541038, ENST00000541518, ENST00000543457, ENST00000875258, ENST00000875259, ENST00000875260

RefSeq mRNA: 5 — MANE Select: NM_001346194 NM_001346194, NM_001346195, NM_001346196, NM_001346197, NM_080818

CCDS: CCDS9482

Canonical transcript exons

ENST00000541038 — 4 exons

Exon	Start	End
ENSE00001365271	96989758	96989809
ENSE00002233109	96985713	96987833
ENSE00002287897	96994298	96994476
ENSE00002306171	96992422	96992572

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 72.16.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	72.16	gold quality
calcaneal tendon	UBERON:0003701	68.97	gold quality
metanephros cortex	UBERON:0010533	67.87	gold quality
minor salivary gland	UBERON:0001830	66.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	65.89	gold quality
rectum	UBERON:0001052	65.74	gold quality
adult mammalian kidney	UBERON:0000082	65.32	gold quality
skin of leg	UBERON:0001511	64.65	gold quality
vermiform appendix	UBERON:0001154	64.41	gold quality
right uterine tube	UBERON:0001302	63.85	gold quality
mouth mucosa	UBERON:0003729	62.83	gold quality
saliva-secreting gland	UBERON:0001044	62.73	gold quality
skin of abdomen	UBERON:0001416	62.61	gold quality
ventricular zone	UBERON:0003053	62.43	gold quality
zone of skin	UBERON:0000014	61.13	gold quality
transverse colon	UBERON:0001157	60.57	gold quality
prefrontal cortex	UBERON:0000451	59.90	gold quality
metanephros	UBERON:0000081	59.74	gold quality
cortex of kidney	UBERON:0001225	59.57	gold quality
mucosa of transverse colon	UBERON:0004991	59.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	59.21	gold quality
smooth muscle tissue	UBERON:0001135	59.19	gold quality
caecum	UBERON:0001153	59.15	gold quality
tendon	UBERON:0000043	58.58	gold quality
esophagus mucosa	UBERON:0002469	58.42	gold quality
left uterine tube	UBERON:0001303	58.40	gold quality
kidney	UBERON:0002113	58.15	gold quality
spinal cord	UBERON:0002240	57.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	56.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting OXGR1, 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-4262	100.00	73.26	3931
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-340-5P	100.00	72.50	4437
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-196A-1-3P	99.99	72.15	2772
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
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-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-95-5P	99.89	72.17	3973

Literature-anchored findings (GeneRIF, showing 6)

• P2Y15 is a cell surface receptor for AMP and adenosine (PMID:15001573)
• Down-Regulation of OXGR1 through DNA Methylation is associated with hepatocellular carcinoma. (PMID:19760608)
• GPR99 was mostly expressed in vascular smooth muscle cells of the nasal mucosa. There was no difference in GPR99 protein levels between allergic and non-allergic nasal mucosa. (PMID:27324180)
• Exercise-induced alpha-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation. (PMID:32104923)
• Changes in expression of orphan receptors GPR99 and GPR107 during the development and establishment of hypertension in spontaneously hypertensive rats. (PMID:33121311)
• OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis. (PMID:36571463)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	oxgr1b	ENSDARG00000029803
danio_rerio	oxgr1a.1	ENSDARG00000033684
danio_rerio	oxgr1a.3	ENSDARG00000040247
danio_rerio	oxgr1a.2	ENSDARG00000078743
mus_musculus	Oxgr1	ENSMUSG00000044819
rattus_norvegicus	Oxgr1	ENSRNOG00000075479

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), P2RY1 (ENSG00000169860), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), FFAR3 (ENSG00000185897), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Protein

Protein identifiers

2-oxoglutarate receptor 1 — Q96P68 (reviewed: Q96P68)

Alternative names: Alpha-ketoglutarate receptor 1, G-protein coupled receptor 80, G-protein coupled receptor 99, P2Y purinoceptor 15, P2Y-like GPCR, P2Y-like nucleotide receptor

All UniProt accessions (4): B2R986, F5H3P1, F5H6U5, Q96P68

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for dicarboxylates and amino dicarboxylates. Receptor for itaconate, a metabolite produced by myeloid lineages. In the respiratory epithelium, couples the binding of itaconate to the activation of GNA11 and downstream intracellular Ca(2+) release, leading to mucocilliary clearance of airborne pathogens. Receptor for leukotriene E4 (LTE4) produced by mast cells upon allergic inflammation. Binds with high affinity to LTE4 and elicits mucin release from pulmonary epithelium in response to airborne fungi allergens. Regulates mucin-producing goblet cell homeostasis. Receptor for alpha-ketoglutarate produced by proximal tubule renal cells upon metabolic alkalosis. In an intrarenal paracrine signaling pathway, binds alpha-ketoglutarate and drives transepithelial salt reabsorption and bicarbonate secretion by SLC26A4/pendrin-positive intercalated cells.

Subcellular location. Cell membrane.

Tissue specificity. Detected in kidney and, to a lower extent, in placenta. Not detected in brain tissues including the frontal cortex, caudate putamen, thalamus, hypothalamus, hippocampus or pons.

Disease relevance. Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis (CAON2) [MIM:620374] A form of nephrolithiasis, a condition in which urinary supersaturation leads to calcium oxalate stone formation in the urinary system. CAON2 is an autosomal dominant form often resultings in nephrocalcinosis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (5): NP_001333123, NP_001333124, NP_001333125, NP_001333126, NP_543008 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (40 total): mutagenesis site 12, topological domain 8, transmembrane region 7, sequence variant 5, glycosylation site 4, sequence conflict 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9VMO	ELECTRON MICROSCOPY	2.4
9VMP	ELECTRON MICROSCOPY	2.5
9VMN	ELECTRON MICROSCOPY	2.6
9UXN	ELECTRON MICROSCOPY	2.7
9VO2	ELECTRON MICROSCOPY	2.7
8YYX	ELECTRON MICROSCOPY	2.84
9UXQ	ELECTRON MICROSCOPY	2.89
9UK2	ELECTRON MICROSCOPY	2.9
9UXP	ELECTRON MICROSCOPY	2.9
9UXO	ELECTRON MICROSCOPY	2.97
8YYW	ELECTRON MICROSCOPY	3.16

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96P68-F1	86.61	0.60

Antibody-complex structures (SAbDab): 1 — 8YYW

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 (1): 106–183

Glycosylation sites (4): 10, 23, 176, 179

Mutagenesis-validated functional residues (12):

Position	Phenotype
106	loss of itaconate-induced intracellular calcium response.
107	slightly decreases itaconate- or alpha-ketoglutarate-induced intracellular calcium response.
110	loss of itaconate-induced receptor endocytosis and intracellular calcium response.
114	markedly impairs itaconate- or alpha-ketoglutarate-induced intracellular calcium response.
118	markedly impairs itaconate- or alpha-ketoglutarate-induced intracellular calcium response.
121	markedly impairs itaconate- or alpha-ketoglutarate-induced intracellular calcium response.
258	loss of itaconate-induced intracellular calcium response.
261	loss of itaconate-induced receptor endocytosis and intracellular calcium response.
264	slightly decreases itaconate- or alpha-ketoglutarate-induced intracellular calcium response.
265	loss of itaconate-induced intracellular calcium response.
285	markedly impairs itaconate- or alpha-ketoglutarate-induced intracellular calcium response.
288	markedly impairs itaconate- or alpha-ketoglutarate-induced intracellular calcium response.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 78 (showing top): MODULE_255, MODULE_317, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, YNGTTNNNATT_UNKNOWN, chr13q32, MODULE_69, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MODULE_37, FOXN3_TARGET_GENES, LMTK3_TARGET_GENES, SIX1_TARGET_GENES

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), innate immune response (GO:0045087), immune system process (GO:0002376), signal transduction (GO:0007165), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), signaling receptor activity (GO:0038023)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR ligand binding	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
immune response	1
defense response to symbiont	1
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
Gq/11-coupled serotonin receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled serotonin receptor signaling pathway	1
transmembrane signaling receptor activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OXGR1	ALDH18A1	P54886	735
OXGR1	LTC4S	Q16873	588
OXGR1	CYSLTR1	Q9Y271	500
OXGR1	CYSLTR2	Q9NS75	488
OXGR1	GPR17	Q13304	487
OXGR1	P2RY12	Q9H244	477
OXGR1	SLC26A4	O43511	419
OXGR1	LTB4R2	Q9NPC1	406
OXGR1	HCAR1	Q9BXC0	381
OXGR1	LTA4H	P09960	355
OXGR1	MCOLN2	Q8IZK6	350
OXGR1	GABRA3	P34903	326
OXGR1	EMB	Q6PCB8	325
OXGR1	ADGRF1	Q5T601	315
OXGR1	SCNN1D	P51172	314

IntAct

8 interactions, top by confidence:

A	B	Type	Score
OXGR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
OXGR1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	OXGR1	psi-mi:“MI:0915”(physical association)	0.400
OXGR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	OXGR1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): OXGR1 (Positive Genetic), OXGR1 (Affinity Capture-MS)

ESM2 similar proteins: A7YY44, B0UXR0, B5X337, D4A4Q2, D4A7K7, O00254, O00398, O08675, P25116, P26824, P30558, P34996, P47749, P47900, P48042, P49019, P49650, P49651, P49652, P55085, P55086, P56488, P59902, P60019, Q00991, Q2HJA4, Q2NNR5, Q3SAG9, Q3U507, Q3U6B2, Q58D85, Q5ZI82, Q6IYF8, Q6XCF2, Q6Y1R5, Q8BLG2, Q920A1, Q920E1, Q924T8, Q924T9

Diamond homologs: A1A5S3, E9QJ73, O08707, P29755, P32248, P33396, P49220, P79785, P97266, Q14330, Q149R9, Q16581, Q28553, Q3T0E9, Q3ZC80, Q4R613, Q58D85, Q5REI5, Q6IYF8, Q6TAC8, Q6Y1R5, Q8K1Z6, Q8NGA4, Q8VIH9, Q920E1, Q924T8, Q95N02, Q96P68, Q99PE3, Q9H1C0, A0A4W3GG95, A5PLE7, A7YY44, D4A7K7, E7F7V7, F1MV99, O00254, O08565, O08858, O18982

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
OXGR1	“up-regulates activity”	GNAS	binding
OXGR1	“up-regulates activity”	GNAL	binding
OXGR1	“up-regulates activity”	GNAI1	binding
OXGR1	“up-regulates activity”	GNAI3	binding
OXGR1	“up-regulates activity”	GNAO1	binding
OXGR1	“up-regulates activity”	GNAZ	binding
OXGR1	“up-regulates activity”	GNAQ	binding
OXGR1	“up-regulates activity”	GNA14	binding
“2-oxoglutaric acid”	“up-regulates activity”	OXGR1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	60
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2502147	NM_001346194.2(OXGR1):c.166del (p.Ser56fs)	Pathogenic
2502149	NM_001346194.2(OXGR1):c.649T>C (p.Cys217Arg)	Pathogenic
2502146	NM_001346194.2(OXGR1):c.371T>G (p.Leu124Arg)	Likely pathogenic
3359195	NM_001346194.2(OXGR1):c.136G>A (p.Val46Met)	Likely pathogenic

SpliceAI

737 predictions. Top by Δscore:

Variant	Effect	Δscore
13:96987773:CATCT:C	acceptor_gain	1.0000
13:96987777:T:C	acceptor_gain	1.0000
13:96987777:T:TC	acceptor_gain	1.0000
13:96992420:A:AC	donor_gain	1.0000
13:96992421:C:CC	donor_gain	1.0000
13:96992421:CA:C	donor_gain	1.0000
13:96992428:AG:A	donor_gain	1.0000
13:96987781:A:T	acceptor_gain	0.9900
13:96987830:CTCG:C	acceptor_gain	0.9900
13:96988848:G:C	donor_gain	0.9900
13:96989805:TTACC:T	acceptor_gain	0.9900
13:96989808:CC:C	acceptor_gain	0.9900
13:96989809:CC:C	acceptor_gain	0.9900
13:96992421:CAA:C	donor_gain	0.9900
13:96992421:CAAT:C	donor_gain	0.9900
13:96992421:CAATT:C	donor_gain	0.9900
13:96992457:G:C	donor_gain	0.9900
13:96992571:TT:T	acceptor_gain	0.9900
13:96994294:TCACC:T	donor_loss	0.9900
13:96994295:CACCT:C	donor_loss	0.9900
13:96994296:ACC:A	donor_loss	0.9900
13:96994297:C:CA	donor_loss	0.9900
13:96987776:C:CC	acceptor_gain	0.9800
13:96987780:C:CT	acceptor_gain	0.9800
13:96987834:C:CC	acceptor_gain	0.9800
13:96989806:TACCC:T	acceptor_loss	0.9800
13:96989807:ACCC:A	acceptor_loss	0.9800
13:96989808:CCCT:C	acceptor_loss	0.9800
13:96989811:T:A	acceptor_loss	0.9800
13:96992573:C:CC	acceptor_gain	0.9800

AlphaMissense

400 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:96987639:C:G	G41R	0.940
13:96987621:C:G	G47R	0.932
13:96987621:C:T	G47R	0.932
13:96987611:C:T	G50D	0.930
13:96987596:A:T	I55K	0.927
13:96987607:A:C	N51K	0.922
13:96987607:A:T	N51K	0.922
13:96987620:C:T	G47E	0.913
13:96987638:C:T	G41D	0.896
13:96987596:A:C	I55R	0.880
13:96987612:C:G	G50R	0.878
13:96987688:G:C	C24W	0.837
13:96987653:A:G	L36P	0.835
13:96987628:G:C	F44L	0.832
13:96987628:G:T	F44L	0.832
13:96987630:A:G	F44L	0.832
13:96987609:T:C	N51D	0.817
13:96987599:A:T	V54E	0.806
13:96987605:G:T	A52E	0.799
13:96987657:A:C	Y35D	0.799
13:96987623:A:T	V46E	0.797
13:96987650:G:T	P37H	0.797
13:96987653:A:T	L36H	0.794
13:96987626:A:C	L45R	0.785
13:96987664:C:A	K32N	0.783
13:96987664:C:G	K32N	0.783
13:96987606:C:G	A52P	0.779
13:96987650:G:C	P37R	0.765
13:96987689:C:G	C24S	0.759
13:96987690:A:T	C24S	0.759

dbSNP variants (sampled 300 via entrez): RS1000161936 (13:96996012 T>C), RS1000193211 (13:96993270 G>A), RS1000215024 (13:96996291 A>G), RS1000224163 (13:96993158 G>A), RS1000564950 (13:96994143 C>T), RS1001100177 (13:96988872 T>C), RS1001104599 (13:96990458 A>G,T), RS1001427261 (13:96989131 G>A), RS1001542832 (13:96991110 T>A), RS1002173185 (13:96996650 T>A), RS1002355872 (13:96993734 C>T), RS1002427896 (13:96993529 A>G), RS1002708006 (13:96988373 T>A), RS1002758206 (13:96988069 G>GA), RS1002930030 (13:96986151 C>T)

Disease associations

OMIM: gene MIM:606922 | disease phenotypes: MIM:620374

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis	Moderate	Autosomal dominant

Mondo (1): nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis (MONDO:0958191)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000121	Nephrocalcinosis
HP:0000787	Nephrolithiasis
HP:0003159	Hyperoxaluria
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0011462	Young adult onset
HP:0012405	Hypocitraturia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004524_4	Energy expenditure (24h)	4.000000e-06
GCST008661_1	Lung function in heavy smokers (high FEV1 vs average FEV1)	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2150840 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Oxoglutarate receptor

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
[3H]LTE4	Agonist	8.6	pKd
α-ketoglutaric acid	Full agonist	4.49	pEC50

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	IC50	2000	nM	CHEMBL2153446
5.30	IC50	5000	nM	CHEMBL2153586
5.16	IC50	7000	nM	CHEMBL2153440

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(1S)-1-[4-(3-chlorophenyl)phenyl]ethyl]-4-(1,8-naphthyridin-2-yl)butanamide	692081: Antagonist activity at human GPR99 receptor expressed in CHO-K1 cells co-expressing Galpha and Gqi5 G-protein assessed as inhibition of succinate-induced increase in intracellular calcium level at by FLIPR assay	ic50	2.0000	uM
2-[4-(3-chlorophenyl)phenyl]-5-[3-(1,8-naphthyridin-2-yl)propyl]-1,3,4-oxadiazole	692081: Antagonist activity at human GPR99 receptor expressed in CHO-K1 cells co-expressing Galpha and Gqi5 G-protein assessed as inhibition of succinate-induced increase in intracellular calcium level at by FLIPR assay	ic50	5.0000	uM
N-[[4-(3-chlorophenyl)phenyl]methyl]-4-(1,8-naphthyridin-2-yl)butanamide	692081: Antagonist activity at human GPR99 receptor expressed in CHO-K1 cells co-expressing Galpha and Gqi5 G-protein assessed as inhibition of succinate-induced increase in intracellular calcium level at by FLIPR assay	ic50	7.0000	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases expression	2
sodium arsenite	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Ketoglutaric Acids	increases activity	1
Methotrexate	increases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2155424	Functional	Antagonist activity at human GPR99 receptor expressed in CHO-K1 cells co-expressing Galpha and Gqi5 G-protein assessed as inhibition of succinate-induced increase in intracellular calcium level at by FLIPR assay	Discovery of a potent and selective small molecule hGPR91 antagonist. — Bioorg Med Chem Lett
CHEMBL4883562	Binding	PRESTO-Tango GPCRome screening (OXGR1)	Data for DCP probe UCSF924

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H490	CHO-K1/OXGR1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU70	U2OS OXGR1 Gq	Cancer cell line	Female
CVCL_KY72	PathHunter CHO-K1 OXGR1 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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