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HCAR2

gene
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Also known as HCA2HM74APUMAGPuma-gNIACR1

Summary

HCAR2 (hydroxycarboxylic acid receptor 2, HGNC:24827) is a protein-coding gene on chromosome 12q24.31, encoding Hydroxycarboxylic acid receptor 2 (Q8TDS4). Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase.

Predicted to enable nicotinic acid receptor activity. Involved in neutrophil apoptotic process and positive regulation of neutrophil apoptotic process. Located in cell junction and plasma membrane.

Source: NCBI Gene 338442 — RefSeq curated summary.

At a glance

  • GWAS associations: 7
  • Clinical variants (ClinVar): 66 total
  • Druggable target: yes — 7 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_177551

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24827
Approved symbolHCAR2
Namehydroxycarboxylic acid receptor 2
Location12q24.31
Locus typegene with protein product
StatusApproved
AliasesHCA2, HM74A, PUMAG, Puma-g, NIACR1
Ensembl geneENSG00000182782
Ensembl biotypeprotein_coding
OMIM609163
Entrez338442

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000328880

RefSeq mRNA: 1 — MANE Select: NM_177551 NM_177551

CCDS: CCDS9235

Canonical transcript exons

ENST00000328880 — 1 exons

ExonStartEnd
ENSE00001294601122701293122703357

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 94.53.

FANTOM5 (CAGE): breadth broad, TPM avg 8.5947 / max 1582.7792, expressed in 329 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1338398.5791327
1338380.01568

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
bloodUBERON:000017894.53gold quality
lower esophagus mucosaUBERON:003583491.98gold quality
esophagus mucosaUBERON:000246989.24gold quality
olfactory segment of nasal mucosaUBERON:000538686.78gold quality
granulocyteCL:000009486.21gold quality
skin of abdomenUBERON:000141685.97gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099185.72gold quality
zone of skinUBERON:000001485.01gold quality
skin of legUBERON:000151184.26gold quality
spleenUBERON:000210681.04gold quality
bone marrowUBERON:000237179.33gold quality
minor salivary glandUBERON:000183078.39gold quality
omental fat padUBERON:001041478.17gold quality
saliva-secreting glandUBERON:000104477.46gold quality
adipose tissueUBERON:000101377.04gold quality
leukocyteCL:000073876.24gold quality
subcutaneous adipose tissueUBERON:000219075.79gold quality
vaginaUBERON:000099675.65gold quality
monocyteCL:000057675.18gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047375.16gold quality
vermiform appendixUBERON:000115474.95gold quality
placentaUBERON:000198774.00gold quality
bone marrow cellCL:000209273.31gold quality
thoracic mammary glandUBERON:000520073.21gold quality
upper lobe of left lungUBERON:000895272.68gold quality
tonsilUBERON:000237272.21gold quality
lungUBERON:000204869.97gold quality
right lungUBERON:000216768.79gold quality
esophagusUBERON:000104366.10gold quality
adult mammalian kidneyUBERON:000008264.56gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

30 targeting HCAR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6758-5P100.0066.211470
HSA-MIR-6856-5P100.0065.471298
HSA-MIR-141-3P99.9472.792421
HSA-MIR-200A-3P99.9472.682420
HSA-MIR-10527-5P99.9172.283754
HSA-MIR-548E-5P99.8972.734486
HSA-MIR-7162-3P99.8968.161682
HSA-MIR-3151-5P99.8663.831069
HSA-MIR-204-5P99.7971.622439
HSA-MIR-211-5P99.7971.652440
HSA-MIR-4766-5P99.7569.232662
HSA-MIR-4446-5P99.7269.192544
HSA-MIR-4755-5P99.7170.342716
HSA-MIR-5006-3P99.7170.262728
HSA-MIR-182799.6368.573265
HSA-MIR-4756-3P99.6266.301319
HSA-MIR-4649-3P99.5666.901783
HSA-MIR-6832-3P99.5270.441726
HSA-MIR-203A-3P99.4970.562806
HSA-MIR-6882-5P99.3571.131206
HSA-MIR-520A-5P99.3566.721632
HSA-MIR-525-5P99.3566.851615
HSA-MIR-146A-3P99.1368.991881
HSA-MIR-92299.0267.231838
HSA-MIR-445198.8268.171455
HSA-MIR-6792-3P98.4166.861359
HSA-MIR-5088-3P98.2966.631310
HSA-MIR-66597.6065.641781
HSA-MIR-6856-3P96.4766.27781
HSA-MIR-3927-5P94.9068.11399

Literature-anchored findings (GeneRIF, showing 40)

  • HM74b has high similarity to HM74 is a receptor for nicotinic acid [HM74b] (PMID:12646212)
  • Our results provided direct evidence indicating that HM74A, but not HM74, was sufficient to mediate anti-lipolytic effect of niacin in adipose tissue. (PMID:16018973)
  • However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. (PMID:16674924)
  • neutrophils express functional GPR109A receptors,which might be involved in the regulation of neutrophil numbers (PMID:17932499)
  • Data show that the high-affinity niacin receptor HM74A is significantly down-regulated in the anterior cingulate cortex of individuals with schizophrenia. (PMID:18639743)
  • Data show that many phenolic acids, including those from the hydroxybenzoic and hydroxycinnamic acid classes, can bind and activate GPR109A (HM74a/PUMA-G), the receptor for the antidyslipidemic agent nicotinic acid. (PMID:19136666)
  • GPR109A receptor plays an important role in the dual regulation of adiponectin secretion and lipolysis (PMID:19141678)
  • Data show that the coordinated PPARgamma-mediated regulation of the GPR81, GPR109A and GPR109B presents a novel mechanism by which TZDs may reduce circulating free fatty acid levels and perhaps ameliorate insulin resistance in obese patients. (PMID:19633298)
  • Data show that Mk-6892 was discovered as full and potent niacin receptor (GPR109A) agonist. (PMID:20184326)
  • these results demonstrate that GPR109A and GPR109B dimerization is a constitutive process occurring early during biosynthesis. (PMID:20380810)
  • The agonist-induced internalization of GPR109A receptors is regulated by GRK2 and arrestin3 in a pertussis toxin-sensitive manner and that internalized receptor recycling is independent of endosomal acidification. (PMID:20460384)
  • niacin-mediated activation of GP109A in liver lowers ABCA1 expression leading to reduced hepatic cholesterol efflux to high density lipoprotein. (PMID:20655299)
  • In contrast, in a squamous cell carcinoma derived cell line, both GPR109A and GPR109B show a more diffuse cellular localization and the receptors are nearly non-functional. (PMID:21655214)
  • upon binding to niacin GPR109A receptors initially activate G(i), leading to dissociation of the Gbetagamma subunit from activated G(i), and subsequently induce ERK1/2 activation via two distinct pathways. (PMID:21768093)
  • Nicotnic acid displays a range of effects that are lipoprotein-independent and potentially antiatherogenic. These effects are mediated by GPR109A. (PMID:22267479)
  • A sequence from residues 329 to 343 in the C-terminal tail of HCA plays a crucial role in keeping HCA in an inactive conformation. (PMID:22962331)
  • Review of the role of GPR109A and its downstream effects in the context of atherosclerosis and vascular inflammation, along with insights into strategy for future drug development. [Review Article] (PMID:23526298)
  • despite NA’s anti-inflammatory effect on human macrophages, it has no effect on foam cells in reverse cholesterol transport; due to GPR109A down-regulation (PMID:23658787)
  • These studies provide key insights into mechanisms by which GPR109A may influence cholesterol efflux in macrophages. (PMID:23770183)
  • Although its functional role is still unknown, HCA2 may be potentially involved in the pathogenesis of various retinopathies and may offer a new therapeutic target. (PMID:24215154)
  • GPR109A is a tumor suppressor in mammary gland. (PMID:24371223)
  • the promiscuous activity exerted by niacin via both GPR109A and GPER may open new avenues towards a better understanding of the mechanisms involved in its biological action exerted in different pathophysiological conditions, including malignant diseases. (PMID:24662263)
  • GPR109A expression is upregulated in blood and substantia nigra in Parkinson disease patients. (PMID:25329911)
  • The results of this study suggested that GPR109A signaling is associated with T2DM, playing a role in regulation of the inflammatory cytokines. (PMID:25361930)
  • These results suggest that the PKC pathway and PDGFR/EGFR transactivation pathway play important roles in HCA2-mediated Akt activation. (PMID:25375133)
  • niacin, at a relatively low concentration, preserves the ability of HMVEC to form tubes under conditions of saturated fatty acid excess, and may elicit this effect through activation of GPR109A (PMID:25463108)
  • Results suggest that the atypical motif asparaging-cysteine-systeine Asn(17)-Cys(18)-Cys(19) is crucial for the normal surface trafficking and function of hydroxycarboxylic acid receptor 2 protein hGPR109A. (PMID:25690651)
  • new insights into the G protein coupling profiles of the HCA receptors and the function of the receptor’s C terminus (PMID:26656756)
  • These results demonstrate that GPR109A is functionally expressed in both human and murine islet beta-cells. (PMID:27570060)
  • GPR109A may inhibit inflammatory cytokine production, induced by palmitic acid, by MIN6 cells possibly via inhibiting the Akt/mTOR signaling pathway. (PMID:29263047)
  • These results indicate that during aging, GPR109A modulates de novo lipid accumulation in liver and adipose tissue, and its dysregulation can lead to age-associated obesity and hepatic steatosis. (PMID:30659164)
  • This review summarizes the use of niacin in treatment of dyslipidemia, the pharmacogenetics of niacin response and the potential role of HCAR2 signaling in the treatment of a variety of inflammatory and metabolic diseases. (PMID:31617441)
  • C. butyricum decreased the fecal secondary BA contents, increased the cecal SCFA quantities, and activated G-protein coupled receptors (GPRs), such as GPR43 and GPR109A. The analysis of clinical specimens revealed that the expression of GPR43 and GPR109A gradually decreased from human normal colonic tissue to adenoma to carcinoma (PMID:31734354)
  • Niacin Ameliorates Hepatic Steatosis by Inhibiting De Novo Lipogenesis Via a GPR109A-Mediated PKC-ERK1/2-AMPK Signaling Pathway in C57BL/6 Mice Fed a High-Fat Diet. (PMID:31858105)
  • Hydroxycarboxylic Acid Receptor 2 Is a Zika Virus Restriction Factor That Can Be Induced by Zika Virus Infection Through the IRE1-XBP1 Pathway. (PMID:32039055)
  • GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics. (PMID:34777363)
  • Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases. (PMID:34852802)
  • Ebola Virus Infection Induces HCAR2 Expression Leading to Cell Death. (PMID:37578011)
  • Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2. (PMID:37932263)
  • [GPR109A partly mediates inhibitory effects of beta-hydroxybutyric acid on lung adenocarcinoma cell proliferation, migration and invasion]. (PMID:37933650)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusHcar2ENSMUSG00000045502
rattus_norvegicusHcar2ENSRNOG00000071408

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY1 (ENSG00000169860), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), FFAR3 (ENSG00000185897), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Protein

Protein identifiers

Hydroxycarboxylic acid receptor 2 — Q8TDS4 (reviewed: Q8TDS4)

Alternative names: G-protein coupled receptor 109A, G-protein coupled receptor HM74A, Niacin receptor 1, Nicotinic acid receptor

All UniProt accessions (2): A0A4Y1JWQ0, Q8TDS4

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox » nicotinuric acid = nicotinamide.

Subcellular location. Cell membrane.

Tissue specificity. Expression largely restricted to adipose tissue and spleen. Expressed on mature neutrophils but not on immature neutrophils or eosinophils.

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

RefSeq proteins (1): NP_808219* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR017452GPCR_Rhodpsn_7TMDomain
IPR051893HCARsFamily

Pfam: PF00001

UniProt features (48 total): helix 14, topological domain 8, strand 8, transmembrane region 7, sequence variant 4, turn 3, chain 1, region of interest 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

40 structures, top 30 by resolution.

PDBMethodResolution (Å)
8J6PELECTRON MICROSCOPY2.55
8J6QELECTRON MICROSCOPY2.6
8JZ7ELECTRON MICROSCOPY2.6
9IZCELECTRON MICROSCOPY2.68
8IJAELECTRON MICROSCOPY2.69
7ZL9X-RAY DIFFRACTION2.7
7ZLYX-RAY DIFFRACTION2.7
9JKYELECTRON MICROSCOPY2.72
9KT8ELECTRON MICROSCOPY2.73
8J6RELECTRON MICROSCOPY2.76
8I7VELECTRON MICROSCOPY2.77
8J6JELECTRON MICROSCOPY2.8
9KT7ELECTRON MICROSCOPY2.8
8IHBELECTRON MICROSCOPY2.85
8JHYELECTRON MICROSCOPY2.87
9IQTELECTRON MICROSCOPY2.9
8J6IELECTRON MICROSCOPY2.92
8IHFELECTRON MICROSCOPY2.97
8JIMELECTRON MICROSCOPY2.98
8H2GELECTRON MICROSCOPY3.01
8J6LELECTRON MICROSCOPY3.05
8IHHELECTRON MICROSCOPY3.06
9IZAELECTRON MICROSCOPY3.06
7XK2ELECTRON MICROSCOPY3.1
8IHIELECTRON MICROSCOPY3.11
8K5CELECTRON MICROSCOPY3.13
8JIIELECTRON MICROSCOPY3.17
8IJBELECTRON MICROSCOPY3.23
8UTDELECTRON MICROSCOPY3.24
8IJDELECTRON MICROSCOPY3.25

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8TDS4-F183.130.58

Antibody-complex structures (SAbDab): 34 — 7XK2, 8H2G, 8I7V, 8I7W, 8IHB, 8IHF, 8IHH, 8IHI, 8IJ3, 8IJA, 8IJB, 8IJD, 8IY9, 8IYH, 8IYW, 8J6I, 8J6J, 8J6L, 8J6P, 8J6Q, 8J6R, 8JER, 8JHN, 8JHY, 8JII (+9 more)

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 328

Disulfide bonds (1): 100–177

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-3296197Hydroxycarboxylic acid-binding receptors
R-HSA-373076Class A/1 (Rhodopsin-like receptors)
R-HSA-418594G alpha (i) signalling events

MSigDB gene sets: 198 (showing top): GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, FOXO4_01, FOXO1_01, GOBP_CELL_CELL_SIGNALING, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, HFH8_01

GO Biological Process (7): neutrophil apoptotic process (GO:0001781), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of neutrophil apoptotic process (GO:0033031), negative regulation of lipid catabolic process (GO:0050995), positive regulation of adiponectin secretion (GO:0070165), apoptotic process (GO:0006915), signal transduction (GO:0007165)

GO Molecular Function (2): nicotinic acid receptor activity (GO:0070553), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (3): plasma membrane (GO:0005886), cell junction (GO:0030054), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Class A/1 (Rhodopsin-like receptors)1
GPCR ligand binding1
GPCR downstream signalling1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
G protein-coupled receptor activity2
cellular anatomical structure2
neutrophil homeostasis1
inflammatory cell apoptotic process1
myeloid cell apoptotic process1
leukocyte apoptotic process1
signal transduction1
neutrophil apoptotic process1
positive regulation of immune system process1
regulation of neutrophil apoptotic process1
positive regulation of myeloid cell apoptotic process1
positive regulation of leukocyte apoptotic process1
negative regulation of catabolic process1
lipid catabolic process1
negative regulation of lipid metabolic process1
regulation of lipid catabolic process1
positive regulation of hormone secretion1
positive regulation of protein secretion1
positive regulation of multicellular organismal process1
adiponectin secretion1
regulation of adiponectin secretion1
programmed cell death1
apoptotic signaling pathway1
execution phase of apoptosis1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
transmembrane signaling receptor activity1
G protein-coupled receptor signaling pathway1
membrane1
cell periphery1

Protein interactions and networks

STRING

836 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HCAR2DENRO43583829
HCAR2SLC5A8Q8N695786
HCAR2FFAR2O15552714
HCAR2FFAR3O14843595
HCAR2OR51E1Q8TCB6570
HCAR2PYYP10082554
HCAR2SLC16A1P53985549
HCAR2IL10P22301538
HCAR2ALDH18A1P54886529
HCAR2GPBAR1Q8TDU6519
HCAR2GPR84Q9NQS5518
HCAR2FOXP3Q9BZS1511
HCAR2IL1BP01584482
HCAR2IL18Q14116481
HCAR2GCGP01275481

IntAct

6 interactions, top by confidence:

ABTypeScore
RAMP1HCAR2psi-mi:“MI:0915”(physical association)0.400
RAMP2HCAR2psi-mi:“MI:0915”(physical association)0.400
HCAR2RAMP2psi-mi:“MI:0915”(physical association)0.400
RAMP3HCAR2psi-mi:“MI:0915”(physical association)0.400
HCAR2RAMP1psi-mi:“MI:0915”(physical association)0.400

ESM2 similar proteins: A0A4W3GG95, A7YY44, B0F9W3, B0UXR0, B2GV46, B3G515, B5X337, E7FEL0, O00398, O46685, O70526, P21556, P25023, P25105, P25116, P26824, P30411, P30558, P32299, P43657, P46002, P46093, P49019, P50132, P56488, Q00991, Q15743, Q1JQB3, Q28642, Q3UFD7, Q4G072, Q4KLH9, Q61038, Q62035, Q80Z39, Q8BFQ3, Q8BFU7, Q8BLG2, Q8BMC0, Q8BUD0

Diamond homologs: B2RPY5, B3DM66, O02664, O02836, O35210, O42384, O77408, O77590, O77621, P08908, P16395, P19327, P21917, P22270, P25095, P25104, P29754, P30555, P30556, P32250, P34969, P34976, P43240, P49019, P49146, P49220, P79113, P97295, Q0EAB6, Q0GBZ5, Q24563, Q25321, Q25322, Q25414, Q2YDN1, Q58CW4, Q5IS62, Q64264, Q6XXX9, Q6XXY0

SIGNOR signaling

1 interactions.

AEffectBMechanism
“bis(2-ethylhexyl) phthalate”“up-regulates activity”HCAR2“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance60
Likely benign2
Benign4

Top pathogenic / likely-pathogenic (0)

SpliceAI

13 predictions. Top by Δscore:

VariantEffectΔscore
12:122702338:T:TAdonor_gain0.3700
12:122702480:CACT:Cdonor_gain0.3300
12:122701943:GCGTC:Gacceptor_gain0.3200
12:122702575:C:CTdonor_gain0.3000
12:122702484:T:TAdonor_gain0.2700
12:122702579:C:CTdonor_gain0.2700
12:122702484:TC:Tdonor_gain0.2600
12:122702578:C:CGdonor_gain0.2600
12:122701986:CT:Cdonor_gain0.2400
12:122702360:CAAAG:Cacceptor_gain0.2400
12:122701945:GTC:Gacceptor_gain0.2100
12:122702361:A:Tacceptor_gain0.2100
12:122702577:A:ACdonor_gain0.2100

AlphaMissense

2431 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:122702552:G:CF244L0.998
12:122702552:G:TF244L0.998
12:122702554:A:GF244L0.998
12:122702830:A:GW152R0.998
12:122702830:A:TW152R0.998
12:122703065:G:CD73E0.998
12:122703065:G:TD73E0.998
12:122703066:T:GD73A0.998
12:122703067:C:GD73H0.998
12:122702942:G:CS114R0.997
12:122702942:G:TS114R0.997
12:122702944:T:GS114R0.997
12:122703066:T:AD73V0.997
12:122703162:C:TG41E0.997
12:122702423:G:CS287R0.996
12:122702423:G:TS287R0.996
12:122702425:T:GS287R0.996
12:122702543:G:CS247R0.996
12:122702543:G:TS247R0.996
12:122702545:T:GS247R0.996
12:122702557:A:GC243R0.996
12:122702564:A:CF240L0.996
12:122702564:A:TF240L0.996
12:122702566:A:GF240L0.996
12:122703005:C:AW93C0.996
12:122703005:C:GW93C0.996
12:122703066:T:CD73G0.996
12:122703078:A:GL69P0.996
12:122703149:A:CN45K0.996
12:122703149:A:TN45K0.996

dbSNP variants (sampled 300 via entrez): RS1000041315 (12:122701481 A>G,T), RS1003056847 (12:122705165 A>C), RS1003487264 (12:122704314 A>G), RS1006507857 (12:122704849 C>A,T), RS1007307432 (12:122701583 G>T), RS1007911414 (12:122703126 C>A,G), RS1010022817 (12:122701555 A>G), RS1010034116 (12:122701728 G>T), RS1010692251 (12:122704448 T>C), RS1010702035 (12:122704679 G>T), RS1010968640 (12:122704133 CTT>C,CT,CTTT), RS1011979212 (12:122705196 T>C,G), RS1013867527 (12:122702157 T>A), RS1013918482 (12:122701171 CTT>C), RS1015495308 (12:122703694 T>C)

Disease associations

OMIM: gene MIM:609163 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

StudyTraitp-value
GCST001463_7Adiponectin levels4.000000e-06
GCST001465_13Adiponectin levels3.000000e-10
GCST002233_9Adiponectin levels7.000000e-06
GCST002935_28Lead levels9.000000e-06
GCST006054_9High altitude adaptation6.000000e-09
GCST009602_67Metabolic syndrome6.000000e-09
GCST90002405_248Reticulocyte count2.000000e-09

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0004502adiponectin measurement
EFO:0009105high altitude adaptation
EFO:0000195metabolic syndrome
EFO:0007986reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3785 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 397,141 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL2107333DIMETHYL FUMARATE422,969
CHEMBL345714ACIPIMOX47,101
CHEMBL573NIACIN4351,963
CHEMBL589586MONOMETHYL FUMARATE411,528
CHEMBL3977835-FLUORONICOTINIC ACID3386
CHEMBL2036958SCH-900271220
CHEMBL278488ACIFRAN23,174

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

PharmGKB variants

2 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2454727HCAR20.000
rs7314976HCAR20.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Hydroxycarboxylic acid receptors

Most potent curated ligand interactions (29 total), top 25:

LigandActionAffinityParameter
SCH 900271Agonist8.7pEC50
MK 6892Full agonist8.4pKi
compound 21 [PMID: 21185185]Full agonist7.92pIC50
compound 2g [PMID: 19309152]Full agonist7.89pIC50
MK 1903Full agonist7.56pEC50
GSK256073Agonist7.5pEC50
compound 43 [PMID: 34781683]Agonist7.4pEC50
Compound 780AAgonist7.4pEC50
compound (+)17a [PMID: 20363624]Full agonist7.35pEC50
(+)-5-(5-bromothiophen-3-yl)-5-methyl-4-oxo-4,5-dihydro-furan-2-carboxylic acidFull agonist7.3pEC50
[3H]nicotinic acidFull agonist7.3pKd
Compound 245AAgonist7.2pEC50
nicotinic acidFull agonist7.2pEC50
5-butyl-1H-pyrazole-3-carboxylic acidPartial agonist7.1pKi
compound 1q [PMID: 18029181]Partial agonist6.85pIC50
compound 9n [PMID: 18752940]Positive6.77pEC50
monomethyl fumarateFull agonist6.74pKi
compound 8f [PMID: 20615702]Full agonist6.41pIC50
acifranFull agonist5.9pEC50
Compound 4a [PMID: 17452318]Agonist5.89pIC50
MK 0354Partial agonist5.78pEC50
acipimoxFull agonist5.6pEC50
compound 42 [PMID: 22420767]Positive5.59pEC50
3-pyridine-acetic acidFull agonist5.3pEC50
5-methyl nicotinic acidFull agonist5.1pEC50

Binding affinities (BindingDB)

18 measured of 18 human assays (18 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
2-{3-[2-(2-chloro-4-hydroxyphenyl)-1,3-thiazol-5-yl]propanamido}benzoic acidIC501 nM
2-{3-[4-(2-chloro-4-hydroxyphenyl)phenyl]propanamido}benzoic acidIC504 nM
2-{3-[3-(5-hydroxypyridin-2-yl)-1,2,4-oxadiazol-5-yl]propanamido}benzoic acidIC504 nM
2-{3-[5-(2-chloro-4-hydroxyphenyl)thiophen-2-yl]propanamido}benzoic acidIC508 nM
2-{3-[4-(5-hydroxypyridin-2-yl)phenyl]propanamido}benzoic acidIC509 nM
2-{3-[3-(4-hydroxyphenyl)-1,2,4-oxadiazol-5-yl]propanamido}benzoic acidIC5010 nM
2-{3-[2-(4-hydroxy-1H-pyrazol-1-yl)-1,3-thiazol-5-yl]propanamido}benzoic acidIC5020 nM
2-{3-[1-(4-hydroxyphenyl)-5-methyl-1H-pyrazol-4-yl]propanamido}benzoic acidIC5024 nM
2-{3-[2-(5-hydroxypyridin-2-yl)-1,3-thiazol-5-yl]propanamido}benzoic acidIC5026 nM
2-{3-[5-(5-hydroxypyridin-2-yl)-1,3-thiazol-2-yl]propanamido}benzoic acidIC5051 nM
2-{3-[1-(5-hydroxypyridin-2-yl)-1H-pyrazol-3-yl]propanamido}benzoic acidIC5058 nM
2-[3-(4-phenylphenyl)propanamido]benzoic acidIC5094 nM
2-{3-[4-(pyridin-2-yl)phenyl]propanamido}benzoic acidIC50120 nM
pyridine-3-carboxylic acidIC50140 nM
2-[3-(naphthalen-2-yl)propanamido]benzoic acidIC50140 nM
2-{3-[5-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]propanamido}benzoic acidIC50330 nM
2-{3-[4-(1H-pyrrol-2-yl)phenyl]propanamido}benzoic acidIC50350 nM
2-[2-(4-methoxyphenoxy)acetamido]benzoic acidEC506000 nM

ChEMBL bioactivities

903 potent at pChembl≥5 of 957 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.02IC500.96nMMONOMETHYL FUMARATE
9.00EC501nMCHEMBL2036954
9.00IC501nMCHEMBL236162
9.00IC501nMCHEMBL483336
9.00IC501nMCHEMBL483337
9.00IC501nMCHEMBL1770352
8.85Ki1.4nMCHEMBL1084657
8.70EC502nMSCH-900271
8.52EC503nMCHEMBL2036951
8.52IC503nMCHEMBL520299
8.52IC503nMCHEMBL483139
8.52Ki3nMCHEMBL1087302
8.52IC503nMCHEMBL1083138
8.52IC503nMCHEMBL1087302
8.40EC504nMCHEMBL2036948
8.40EC504nMCHEMBL2036955
8.40IC504nMCHEMBL235256
8.40IC504nMCHEMBL237248
8.40IC504nMCHEMBL483353
8.40IC504nMCHEMBL485196
8.40Ki4nMCHEMBL237248
8.40Ki4nMCHEMBL1086656
8.40Ki4nMCHEMBL1086657
8.40IC504nMCHEMBL1087302
8.40IC504nMCHEMBL1084576
8.40IC504nMCHEMBL1770353
8.30EC505nMCHEMBL2036950
8.30IC505nMCHEMBL483352
8.30IC505nMCHEMBL520513
8.30IC505nMCHEMBL1085616
8.30IC505nMCHEMBL1085156
8.30IC505nMCHEMBL1770355
8.22EC506nMCHEMBL236162
8.22IC506nMCHEMBL483140
8.22IC506nMCHEMBL1086354
8.22IC506nMCHEMBL1084799
8.22EC506nMCHEMBL1085589
8.22IC506nMCHEMBL1086541
8.22IC506nMCHEMBL237248
8.19EC506.5nMCHEMBL483139
8.15EC507nMCHEMBL2036960
8.15IC507nMCHEMBL1084030
8.15IC507nMCHEMBL1085148
8.13EC507.4nMCHEMBL2057602
8.13IC507.4nMCHEMBL1085414
8.10IC508nMCHEMBL235954
8.10IC508nMCHEMBL521326
8.10Ki8nMCHEMBL1086656
8.10IC508nMCHEMBL482698
8.10IC508nMCHEMBL1086353

PubChem BioAssay actives

929 with measured affinity, of 1850 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-[3-[2-(2-chloro-4-hydroxyphenyl)-1,3-thiazol-5-yl]propanoylamino]benzoic acid1798331: Tritiated Niacin Binding Assay and [35S]-GTP-gammaS Binding Assay from Article 10.1021/jm700942d: “Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.”ic500.0010uM
2-[[(2S)-2-amino-3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]benzoic acid594510: Displacement of [3H]nicotinic acid from human GPR109A receptoric500.0010uM
2-[3-(6-chloro-7-oxo-2H-benzo[g][1,2]benzoxazol-3-yl)propanoylamino]cyclohexene-1-carboxylic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0010uM
2-[3-(7-hydroxypyrazolo[1,5-a]quinolin-3-yl)propanoylamino]cyclohexene-1-carboxylic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0010uM
Monomethyl Fumarate2038662: Agonist activity at Niacin receptor (unknown origin)ic500.0010uM
5-(2-cyclobutylethyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0010uM
2-[[2,2,3,3-tetrafluoro-3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]cyclohexene-1-carboxylic acid464646: Displacement of [3H]NA from cloned human GPR109A receptor expressed in CHO-K1 cells by spectrophotometryki0.0014uM
5-[3-(1-methylcyclopropyl)propyl]-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0020uM
2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]cyclohexene-1-carboxylic acid464646: Displacement of [3H]NA from cloned human GPR109A receptor expressed in CHO-K1 cells by spectrophotometryki0.0030uM
2-[3-(7-oxo-2H-benzo[g][1,2]benzoxazol-3-yl)propanoylamino]benzoic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0030uM
2-[3-(7-oxo-2H-benzo[g][1,2]benzoxazol-3-yl)propanoylamino]cyclohexene-1-carboxylic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0030uM
5-(3,5-difluorophenyl)-2-[3-(6-hydroxynaphthalen-2-yl)propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0030uM
5-(4,4-difluorobutyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0030uM
2-[3-[4-(2-chloro-4-hydroxyphenyl)phenyl]propanoylamino]benzoic acid1798331: Tritiated Niacin Binding Assay and [35S]-GTP-gammaS Binding Assay from Article 10.1021/jm700942d: “Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.”ic500.0040uM
2-[3-(7-hydroxy-4,5-dihydrobenzo[g][1,2]benzoxazol-3-yl)propanoylamino]cyclohexene-1-carboxylic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0040uM
2-[[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]-2-methylpropanoyl]amino]cyclohexene-1-carboxylic acid464646: Displacement of [3H]NA from cloned human GPR109A receptor expressed in CHO-K1 cells by spectrophotometryki0.0040uM
2-[[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]-2,2-dimethylpropanoyl]amino]cyclohexene-1-carboxylic acid464646: Displacement of [3H]NA from cloned human GPR109A receptor expressed in CHO-K1 cells by spectrophotometryki0.0040uM
2-[3-(7-hydroxy-4,5-dihydrobenzo[g][1,2]benzoxazol-3-yl)propanoylamino]benzoic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0040uM
2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]benzoic acid1798331: Tritiated Niacin Binding Assay and [35S]-GTP-gammaS Binding Assay from Article 10.1021/jm700942d: “Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.”ic500.0040uM
2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]-5-propylcyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0040uM
2-[[(2R)-2-amino-3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]benzoic acid594510: Displacement of [3H]nicotinic acid from human GPR109A receptoric500.0040uM
5-(3-cyclopropylpropyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0040uM
5-(3-methylbutyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0040uM
2-[3-(7-oxo-1,2-dihydrobenzo[g]indazol-3-yl)propanoylamino]benzoic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0050uM
2-[[(2S)-2-amino-3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]cyclohexene-1-carboxylic acid594510: Displacement of [3H]nicotinic acid from human GPR109A receptoric500.0050uM
5-(4-methylpentyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0050uM
2-[3-(6-hydroxyimidazo[2,1-b][1,3]benzothiazol-2-yl)propanoylamino]cyclohexene-1-carboxylic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0050uM
2-[3-[1-(5-hydroxy-2-pyridinyl)pyrazol-3-yl]propanoylamino]cyclohexene-1-carboxylic acid482998: Displacement of [3H]niacin from GRP109A receptoric500.0050uM
5-(3,5-difluorophenyl)-2-[[3-[1-(5-hydroxy-2-pyridinyl)pyrazol-3-yl]-2-methylpropanoyl]amino]cyclohexene-1-carboxylic acid482998: Displacement of [3H]niacin from GRP109A receptoric500.0050uM
(4S,5R)-2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]-4-methyl-5-(2,3,5-trifluorophenyl)cyclohexene-1-carboxylic acid484758: Agonist activity at human niacin receptor expressed in CHO-KI cells by [35S]GTPgammaS binding assayec500.0060uM
2-[3-(6-fluoro-7-oxo-2H-benzo[g][1,2]benzoxazol-3-yl)propanoylamino]cyclohexene-1-carboxylic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0060uM
5-butyl-2-[3-(6-hydroxynaphthalen-2-yl)propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0060uM
4-(2,3-difluorophenyl)-2-[[3-[1-(5-hydroxy-2-pyridinyl)pyrazol-3-yl]-2-methylpropanoyl]amino]cyclohexene-1-carboxylic acid482998: Displacement of [3H]niacin from GRP109A receptoric500.0060uM
(4S,5R)-2-[3-[3-(5-fluoro-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]-4-methyl-5-(2,3,5-trifluorophenyl)cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0060uM
5-(3-fluorophenyl)-2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0070uM
2-[3-[1-(5-hydroxy-2-pyridinyl)-5-methylpyrazol-4-yl]propanoylamino]cyclohexene-1-carboxylic acid482998: Displacement of [3H]niacin from GRP109A receptoric500.0070uM
5-[3-(1-chlorocyclopropyl)propyl]-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione663584: Agonist activity at human recombinant GPR109a expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulationec500.0070uM
5-(3-fluorophenyl)-2-[3-(6-hydroxynaphthalen-2-yl)propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0074uM
(2R,3R,4S)-3-(cyclopropylmethyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxylic acid672092: Agonist activity at human GPR109a expressed in CHO cells assessed as decrease in forskolin-stimulated cAMP production by HTRF assayec500.0074uM
2-[3-(7-hydroxytriazolo[1,5-a]quinolin-3-yl)propanoylamino]benzoic acid353308: Displacement of [3H]niacin from human GPR109A expressed in CHO cellsic500.0080uM
2-[3-[5-(2-chloro-4-hydroxyphenyl)thiophen-2-yl]propanoylamino]benzoic acid1798331: Tritiated Niacin Binding Assay and [35S]-GTP-gammaS Binding Assay from Article 10.1021/jm700942d: “Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.”ic500.0080uM
(4S,5R)-5-(3-fluorophenyl)-2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]-4-methylcyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0080uM
2-[3-(6-hydroxynaphthalen-2-yl)propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0080uM
2-[3-(6-hydroxynaphthalen-2-yl)propanoylamino]-5-propylcyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0080uM
5-(4-fluorophenyl)-2-[3-(6-hydroxynaphthalen-2-yl)propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0086uM
niacin301341: Agonist activity at human GPR109a expressed in human adipocytes assessed as decrease in intracellular cAMP level by HTRF assayec500.0087uM
2-[3-[4-(5-hydroxy-2-pyridinyl)phenyl]propanoylamino]benzoic acid1798331: Tritiated Niacin Binding Assay and [35S]-GTP-gammaS Binding Assay from Article 10.1021/jm700942d: “Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.”ic500.0090uM
5-(6-fluoro-3-pyridinyl)-2-[3-[3-(5-hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]propanoylamino]cyclohexene-1-carboxylic acid484757: Displacement of [3H]niacin from human niacin receptor expressed in CHO-KI cellsic500.0090uM
2-[5-(2-chloro-4-hydroxyphenyl)pent-4-ynoylamino]cyclohexene-1-carboxylic acid1487434: Agonist activity at recombinant human HCA2 receptor expressed in Flp-IN HEK cells assessed as reduction in forskolin-stimulated cAMP accumulation measured after 30 minsec500.0090uM
2-[[3-[1-(5-hydroxy-2-pyridinyl)pyrazol-3-yl]-2-methylpropanoyl]amino]-4-propylcyclohexene-1-carboxylic acid482998: Displacement of [3H]niacin from GRP109A receptoric500.0090uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Niacinincreases activity, increases expression, increases reaction, affects activity, increases phosphorylation (+3 more)11
Cyclic AMPdecreases reaction, increases abundance, increases activity, decreases abundance, affects binding3
Estradiolaffects cotreatment, decreases expression3
sodium arsenitedecreases expression, increases expression2
acifranincreases phosphorylation, increases reaction, affects binding, increases activity2
Air Pollutantsdecreases expression, increases abundance2
Benzo(a)pyrenedecreases methylation, increases mutagenesis2
Colforsindecreases reaction, increases abundance, increases activity, affects binding2
Nicotinic Acidsincreases activity, increases phosphorylation, affects binding, increases abundance, increases reaction (+1 more)2
Pyrazolesaffects binding, increases activity2
Cadmium Chloridedecreases expression, increases abundance, increases expression2
3-Hydroxybutyric Aciddecreases reaction, increases abundance, affects binding, increases activity2
Particulate Matterdecreases expression, increases abundance2
ortho-Aminobenzoatesaffects binding, increases activity2
aristolochic acid Iincreases expression1
GSK-J4increases expression1
bisphenol Faffects cotreatment, decreases expression1
alpha phellandreneincreases expression1
triphenyl phosphateaffects expression1
cinnamic acidaffects binding1
3-phenylpropionic acidaffects binding, increases activity1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression, affects cotreatment1
di-n-butylphosphoric acidaffects expression1
citraconic acidaffects binding, increases activity1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-onedecreases reaction, increases activity, increases phosphorylation1
abrineincreases expression1
gardiquimoddecreases reaction, increases expression1
MK 6892increases activity, affects binding1
Leflunomideincreases expression1
Arachidonic Acidsincreases abundance, increases activity, increases phosphorylation, increases reaction1

ChEMBL screening assays

135 unique, capped per target: 80 functional, 53 binding, 1 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1002173FunctionalAgonist activity against human GPR109a assessed as forskolin-induced cAMP accumulation3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice. — J Med Chem
CHEMBL1002177BindingDisplacement of [3H]nicotinic acid from human GPR109a receptor expressed in CHO cells3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice. — J Med Chem
CHEMBL3788712ADMETActivation of GPR109A in human A431 cells assessed as suppression of forskolin-induced cAMP production after 30 minsSynthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid. — J Med Chem

Cellosaurus cell lines

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

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

CellosaurusNameCategorySex
CVCL_H469CHO-K1/NIACR1/Galpha15Spontaneously immortalized cell lineFemale
CVCL_KV27cAMP Hunter CHO-K1 GPR109A GiSpontaneously immortalized cell lineFemale
CVCL_KX22PathHunter CHO-K1 GPR109A beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_ZL11Tango GPR109A-bla U2OSCancer cell lineFemale

Clinical trials (associated diseases)

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

About this page

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alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot