ADIPOR2

Summary

ADIPOR2 (adiponectin receptor 2, HGNC:24041) is a protein-coding gene on chromosome 12p13.33, encoding Adiponectin receptor protein 2 (Q86V24). Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism.

The adiponectin receptors, ADIPOR1 (MIM 607945) and ADIPOR2, serve as receptors for globular and full-length adiponectin (MIM 605441) and mediate increased AMPK (see MIM 602739) and PPAR-alpha (PPARA; MIM 170998) ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin (Yamauchi et al., 2003 [PubMed 12802337]).

Source: NCBI Gene 79602 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 59 total — 21 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_024551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24041
Approved symbol	ADIPOR2
Name	adiponectin receptor 2
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	PAQR2, ACDCR2
Ensembl gene	ENSG00000006831
Ensembl biotype	protein_coding
OMIM	607946
Entrez	79602

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 41 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000357103, ENST00000535774, ENST00000537190, ENST00000537545, ENST00000540974, ENST00000543456, ENST00000544470, ENST00000878963, ENST00000878964, ENST00000878965, ENST00000878966, ENST00000878967, ENST00000878968, ENST00000878969, ENST00000878970, ENST00000878971, ENST00000878972, ENST00000878973, ENST00000878974, ENST00000878975, ENST00000878976, ENST00000878977, ENST00000878978, ENST00000878979, ENST00000878980, ENST00000878981, ENST00000878982, ENST00000878983, ENST00000878984, ENST00000878985, ENST00000878986, ENST00000878987, ENST00000878988, ENST00000878989, ENST00000878990, ENST00000878991, ENST00000878992, ENST00000878993, ENST00000878994, ENST00000878995, ENST00000878996, ENST00000924874, ENST00000924875, ENST00000924876, ENST00000924877, ENST00000924878, ENST00000969120

RefSeq mRNA: 4 — MANE Select: NM_024551 NM_001375363, NM_001375364, NM_001375365, NM_024551

CCDS: CCDS8511

Canonical transcript exons

ENST00000357103 — 8 exons

Exon	Start	End
ENSE00000712257	1783880	1784073
ENSE00000816807	1780451	1780637
ENSE00000816808	1780889	1781076
ENSE00001402644	1785944	1788674
ENSE00001426014	1691070	1691191
ENSE00003468776	1754258	1754514
ENSE00003512544	1777854	1778025
ENSE00003616430	1772842	1772961

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9067 / max 536.2809, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123384	37.2788	1822
123391	0.4146	187
123390	0.1476	60
123389	0.0657	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	97.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.64	gold quality
right adrenal gland cortex	UBERON:0035827	96.88	gold quality
right lung	UBERON:0002167	96.65	gold quality
right adrenal gland	UBERON:0001233	96.50	gold quality
left adrenal gland	UBERON:0001234	96.12	gold quality
left adrenal gland cortex	UBERON:0035825	96.04	gold quality
substantia nigra	UBERON:0002038	95.96	gold quality
adrenal gland	UBERON:0002369	95.92	gold quality
lower esophagus mucosa	UBERON:0035834	95.77	gold quality
liver	UBERON:0002107	95.35	gold quality
colonic epithelium	UBERON:0000397	95.34	gold quality
adrenal tissue	UBERON:0018303	95.21	gold quality
Ammon’s horn	UBERON:0001954	94.54	gold quality
duodenum	UBERON:0002114	94.52	gold quality
tibial nerve	UBERON:0001323	94.46	gold quality
omental fat pad	UBERON:0010414	94.45	gold quality
adipose tissue	UBERON:0001013	94.44	gold quality
right lobe of liver	UBERON:0001114	94.38	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.33	gold quality
amygdala	UBERON:0001876	94.02	gold quality
temporal lobe	UBERON:0001871	93.99	gold quality
putamen	UBERON:0001874	93.87	gold quality
body of stomach	UBERON:0001161	93.70	gold quality
rectum	UBERON:0001052	93.67	gold quality
upper lobe of left lung	UBERON:0008952	93.65	gold quality
stomach	UBERON:0000945	93.46	gold quality
thoracic mammary gland	UBERON:0005200	93.37	gold quality
lung	UBERON:0002048	93.23	gold quality
skeletal muscle tissue	UBERON:0001134	93.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, FOXO1, NR3C1, PPARG

miRNA regulators (miRDB)

184 targeting ADIPOR2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-34C-5P	99.97	70.45	1577

Literature-anchored findings (GeneRIF, showing 40)

• cloning of cDNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning [AdipoR1 & AdipoR2] (PMID:12802337)
• Here we report the marked expression of mRNAs for the adiponectin receptors AdipoR1 and AdipoR2 in human and rat pancreatic beta cells, at levels similar to liver and greater than muscle. (PMID:14651988)
• Epression levels of AdipoRw as well as plasma adiponectin concentration were lower in people with a family history of Type 2. (PMID:15105989)
• myotube mRNA levels of both receptors are associated with distinct metabolic functions but not with insulin sensitivity; AdipoR1, but not AdipoR2, expression correlated with insulin secretion. (PMID:15331527)
• a link between adiponectin and bone homeostasis by demonstrating transcription, translation, and secretion of adiponectin, as well as expression of its receptors, AdipoR1 and AdipoR2, in bone-forming cells (PMID:15454091)
• Plasma adiponection and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by adipose tissue lipolysis and/or plasma FFA. Adiponectin is abundantly expressed in muscle and is present in/on sarcolemma of muscle fibres. (PMID:15757860)
• Genetic variations in ADIPOR2 are unlikely to lead to a common genetic predisposition to insulin resistance or type 2 diabetes in the Japanese population. (PMID:15918014)
• Evidence for association between variation in the adiponectin receptor 2 and type 2 diabetes among Amish. (PMID:15983228)
• In patients with chronic hepatitis c, adiponectin and receptors(AdipoR1 and AdipoR2)play a role in hepatic inflammation in both sexes and liver steatosis in males. (PMID:16139921)
• adiponectin receptors have roles in the human endometrium (PMID:16601138)
• Rosiglitazone can elevate the expression of ADIPOR2 in hepatocytes which caninteract functionally with a glucocorticoid receptor in the ADIPOR2 promoter to mediate stimulation of transcription. (PMID:16609881)
• Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase (PMID:16678125)
• 3 variants were found: (+795G/A, +870C/A & +963C/T) in linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype had higher plasma adiponectin levels & lower fasting triglyceride, VLDL-triglyceride & VLDL-cholesterol levels. (PMID:16700915)
• may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer. (PMID:16899222)
• Upregulated in insulin-resistant women with polycystic ovary syndrome. (PMID:17001470)
• Reduced circulating adiponectin occurs in rat fatty liver disease, but it is elevated in a mouse cirrhosis with similar findings in humans. Diminished hepatic expression of adiponectin receptors (AdipoR2 and AdipoR1) was only found in liver cirrhosis. (PMID:17006986)
• We observed the expression of adiponectin, AdipoR1 and AdipoR2 in the MG-63 cell line and the osteoblastic cell line differentiated from human mesenchymal stem cells. (PMID:17054465)
• AdipoR1 and AdipoR2 are integral membrane proteins with the predicted topology–an intracellular N-terminus and an extracellular C-terminus (PMID:17118803)
• possibility that adiponectin might modulate the growth of normal breast epithelial cells and breast cancer cells directly through AdipoR1 and AdipoR2 receptors (PMID:17123704)
• Genetic variation in ADIPOR2 is not a major cause of extreme insulin resistance in humans, nor does it contribute in a significant manner to type 2 diabetes risk and related traits in UK Europid populations. (PMID:17216283)
• No support for a relation between ADIPOR2 variability and risk of type 2 diabetes in women. (PMID:17416799)
• Plasma adiponectin and muscle gene expression of its specific receptors are controlled by genetic and several specific nongenetic factors (PMID:17426101)
• Adiponectin negatively regulates the progression of gastric cancer cells possibly through AdipoR2. (PMID:17459059)
• Lower AdipoR after kidney transplantation may be secondary to immunosuppression and/or an improvement in glomerular filtration rate and the uremic milieu. (PMID:17697862)
• role of polymorphisms in the adiponectin receptor 1 and 2 genes (ADIPOR1 and ADIPOR2) in insulin resistance and type 2 diabetes [review] (PMID:17716299)
• +33371 A/G polymorphism is associated with increased risk of T2DM and multiple insulin resistance-related phenotypes (including fasting plasma glucose, fasting serum triglycerides, and BMI) in the Chinese population (PMID:18075289)
• evated ADIPOR2 expression is associated with colorectal carcinomas but not in gastrointestinal stromal tumors (PMID:18310295)
• Dexamethasone inhibits AdipoR2 mRNA expression in nondiabetic subjects. (PMID:18363889)
• None of the SNPs in either ADIPOR1 or ADIPOR2 were associated with the risk of type 2 diabetes in Koreans. SNPs of ADIPOR2 were associated with waist circumference. (PMID:18466348)
• Expression of AIDIPOR2 was determined in livers of morbidly obese patients with non-alcoholic fatty liver disease. (PMID:18713296)
• ADIPOR2 SNPs are associated with liver function tests in T2DM subjects, suggesting a possible role of this receptor in liver dysfunction associated with insulin resistance. (PMID:18719649)
• In a HEK293 cell model, we found that downregulating AdipoR1/R2 simultaneously, but not individually, by RNA interference attenuated adiponectin-induced ERK1/2 activation, suggesting that either receptor was sufficient to mediate the response. (PMID:18842004)
• AdipoR2 is overexpressed in liver in obese patients with nonalcoholic steatohepatitis. (PMID:18923878)
• Upregulation in endothelial cells potentiates the antiinflammatory effect of adiponectin, which may apply to cardiovascular complcation in diabetes. (PMID:18988888)
• The lack of correlation between changes in SAT adiponectin gene and protein expression and its circulating levels suggests that adipose tissue synthesis and release of adiponectin are highly regulated pathways. (PMID:18996753)
• In whites, six SNPs in ADIPOQ, one SNP in ADIPOR1 and one SNP in ADIPOR2 were associated with insulin sensitivity at the P<0.05 level. (PMID:19037660)
• Pancreatic cancer expresses adiponectin receptor2 and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study (PMID:19051043)
• The distribution of adiponectin receptors on human peripheral blood mononuclear cells. (PMID:19120283)
• Genetic variation, particularly in the ADIPOR2 gene, contributes to variation in hepatic fat accumulation in humans (PMID:19208777)
• Expression of Adipo-R2, but not Adipo-R1, is observed in the cytoplasm of both placental cytotrophoblasts and syncytiotrophoblasts of mild preeclempsia, severe cases and normal pregnancy group. (PMID:19487733)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adipor2	ENSDARG00000101849
mus_musculus	Adipor2	ENSMUSG00000030168
rattus_norvegicus	Adipor2	ENSRNOG00000007990

Paralogs (10): MMD (ENSG00000108960), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Adiponectin receptor protein 2 — Q86V24 (reviewed: Q86V24)

Alternative names: Progestin and adipoQ receptor family member 2, Progestin and adipoQ receptor family member II

All UniProt accessions (1): Q86V24

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism. Required for normal body fat and glucose homeostasis. ADIPOQ-binding activates a signaling cascade that leads to increased PPARA activity, and ultimately to increased fatty acid oxidation and glucose uptake. Has intermediate affinity for globular and full-length adiponectin. Required for normal revascularization after chronic ischemia caused by severing of blood vessels.

Subunit / interactions. May form homooligomers and heterooligomers with ADIPOR1. Interacts with APPL2 (via BAR domain); ADIPOQ dissociates this interaction.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous. Highly expressed in skeletal muscle, liver and placenta. Weakly expressed in brain, heart, colon, spleen, kidney, thymus, small intestine, peripheral blood leukocytes and lung.

Domain organisation. The N-terminus is cytoplasmic and the C-terminus is extracellular, contrary to what is observed for G-protein coupled receptors. Unlike G-protein coupled receptors, transmembrane helices are not kinked or tilted relative to the plane of the membrane.

Similarity. Belongs to the ADIPOR family.

RefSeq proteins (4): NP_001362292, NP_001362293, NP_001362294, NP_078827* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

Enzyme classification (BRENDA):

• EC 3.5.1.23 — ceramidase (BRENDA: 26 organisms, 303 substrates, 355 inhibitors, 64 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

43 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-LAUROYLSPHINGOSINE	0.149–0.4132	5
D-ERYTHRO-C12-4-NITROBENZO-2-OXA-1,3-DIAZOLE-CER	0.0393–0.0601	3
N-[12-[(7-NITRO-2-1,3-BENZOXADIAZOL-4-YL)AMINE]D	0.0155–0.066	3
(2R,3Z)-2-([(2E)-1-HYDROXY-12-[(7-NITRO-2,1,3-BE	0.087–0.19	2
N-[(2S,3R,4E)-1,3-DIHYDROXY-14-[(7-NITRO-2,1,3-B	0.193–0.204	2
N-[(2S,3R,4E)-1,3-DIHYDROXYNONADEC-4-EN-2-YL]-12	0.085–0.11	2
N-[(2S,3R,4E)-13-[[9-(ETHYLAMINO)-5-OXO-5H-BENZO	0.036–0.082	2
N-[(2S,3R,4E)-7-[[9-(DIETHYLAMINO)-5-OXO-5H-BENZ	0.1418–0.1818	2
(13E)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1	0.033	1
(15E)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1	0.04	1
(2R)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1-	0.042	1
(2S)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1-	0.021	1
(4E,2S,3R)-2-N-(10-PYRENEDECANOYL)-1,3,17-TRIHYD	0.0005	1
(9E)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1-	0.139	1
2,4-DIDEOXY-2-(HEXADECANOYLAMINO)-5-O-(2-OXO-2H-	0.016	1

UniProt features (49 total): helix 15, topological domain 8, transmembrane region 7, mutagenesis site 4, turn 4, binding site 3, sequence variant 2, strand 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5LWY	X-RAY DIFFRACTION	2.4
5LX9	X-RAY DIFFRACTION	2.4
6KS1	X-RAY DIFFRACTION	2.4
6YX9	X-RAY DIFFRACTION	2.4
6YXD	X-RAY DIFFRACTION	2.9
5LXA	X-RAY DIFFRACTION	3
6YXG	X-RAY DIFFRACTION	3.01
6YXF	X-RAY DIFFRACTION	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V24-F1	82.69	0.70

Antibody-complex structures (SAbDab): 8 — 5LWY, 5LX9, 5LXA, 6KS1, 6YX9, 6YXD, 6YXF, 6YXG

Functional residue map

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

Ligand- & substrate-binding residues (3): 202; 348; 352

Mutagenesis-validated functional residues (4):

Position	Phenotype
202	abolishes response to adipoq binding; when associated with a-219; a-348 and a-352.
219	impairs response to adipoq binding. abolishes response to adipoq binding; when associated with a-202; a-348 and a-352.
348	impairs response to adipoq binding. abolishes response to adipoq binding; when associated with a-202; a-219 and a-352.
352	abolishes response to adipoq binding; when associated with a-202; a-219 and a-348.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163680	AMPK inhibits chREBP transcriptional activation activity

MSigDB gene sets: 293 (showing top): GOBP_LIPID_MODIFICATION, MODULE_52, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, PAX4_01, MODULE_255, GOBP_RESPONSE_TO_PEPTIDE, TGCACTT_MIR519C_MIR519B_MIR519A, MODULE_151, ATACCTC_MIR202, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, MODULE_317, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_WOUND_HEALING, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY

GO Biological Process (8): hormone-mediated signaling pathway (GO:0009755), fatty acid oxidation (GO:0019395), adiponectin-activated signaling pathway (GO:0033211), glucose homeostasis (GO:0042593), vascular wound healing (GO:0061042), positive regulation of cold-induced thermogenesis (GO:0120162), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (6): signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), metal ion binding (GO:0046872), adiponectin binding (GO:0055100), adipokinetic hormone receptor activity (GO:0097003), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Integration of energy metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
signal transduction	1
cellular response to hormone stimulus	1
fatty acid metabolic process	1
lipid oxidation	1
hormone-mediated signaling pathway	1
cytokine-mediated signaling pathway	1
carbohydrate homeostasis	1
angiogenesis involved in wound healing	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
molecular transducer activity	1
cation binding	1
hormone binding	1
protein-hormone receptor activity	1
adiponectin binding	1
adipokinetic hormone binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADIPOR2	ADIPOQ	Q15848	999
ADIPOR2	APPL1	Q9UKG1	995
ADIPOR2	LEP	P41159	898
ADIPOR2	PPARA	Q07869	897
ADIPOR2	ADIPOR1	Q96A54	885
ADIPOR2	RETN	Q9HD89	869
ADIPOR2	CDH13	P55290	869
ADIPOR2	NAMPT	P43490	822
ADIPOR2	PPARGC1A	Q9UBK2	794
ADIPOR2	RETNLB	Q9BQ08	735
ADIPOR2	INS	P01308	735
ADIPOR2	RARRES2	Q99969	692
ADIPOR2	GAD1	Q99259	672
ADIPOR2	CAMKK2	Q96RR4	652
ADIPOR2	SIRT1	Q96EB6	632

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TMBIM6	ADIPOR2	psi-mi:“MI:0915”(physical association)	0.560
ADIPOR2	NCK1	psi-mi:“MI:0914”(association)	0.350
ADIPOR2	NCK2	psi-mi:“MI:0914”(association)	0.350
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
TCTN2	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
APPL1	ADIPOR2	psi-mi:“MI:2364”(proximity)	0.270
ADIPOR2	APPL1	psi-mi:“MI:2364”(proximity)	0.270
TMBIM6	ADIPOR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (131): NCK1 (Affinity Capture-MS), RNF181 (Affinity Capture-MS), APPL1 (Two-hybrid), ADIPOR2 (Proximity Label-MS), ADIPOR2 (Proximity Label-MS), RNF181 (Affinity Capture-MS), NCK1 (Affinity Capture-MS), ADIPOR2 (Affinity Capture-MS), TMBIM6 (Two-hybrid), ADIPOR2 (Affinity Capture-RNA), NEU2 (Affinity Capture-MS), RNF181 (Affinity Capture-MS), NCK2 (Affinity Capture-MS), DUSP6 (Affinity Capture-MS), ADIPOR2 (Affinity Capture-Western)

ESM2 similar proteins: A0A0E0RQ52, A2QTJ1, A8WZU4, B3A0L9, B3A0M2, C5DI25, C8VCL4, E9ECB5, G2WYP9, O13353, O49323, P0CS66, P0CS67, P34535, P40528, P48017, P51830, P53224, Q01285, Q09910, Q0U2R3, Q0VC89, Q0WQK2, Q22271, Q22712, Q38E53, Q38E56, Q3EBC2, Q4WC37, Q5BLG4, Q5W0Z9, Q5Y5T1, Q6BLY8, Q6CUB5, Q86ME2, Q86V24, Q8BQQ1, Q8BQS5, Q8I0G4, Q8IZN3

Diamond homologs: A8WZU4, Q09749, Q09910, Q12442, Q6ETK9, Q84N34, Q86V24, Q8BQS5, Q91VH1, Q94177, Q96A54, Q9VCY8, B7F9G7, Q10PI5, Q7ZVH1, Q865K9, Q8TEZ7, Q93ZH9, Q9SVF3, Q9SZG0, Q9ZUH8, Q03419, Q753H5, Q80ZE4, Q6TCH7, Q07959, Q6TCG8, Q75F81, Q8N4S7, Q9JJE4, Q6TCG2, Q6TCG5, Q6TCH4, Q6ZVX9, Q6DC77

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ADIPOQ	up-regulates	ADIPOR2	binding
ADIPOR2	up-regulates	APPL1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	1
Uncertain significance	22
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
147092	GRCh38/hg38 12p13.33(chr12:54452-2558097)x1	Pathogenic
147690	GRCh38/hg38 12p13.33-13.31(chr12:199896-5807366)x1	Pathogenic
148625	GRCh38/hg38 12p13.33(chr12:80412-2850599)x1	Pathogenic
149561	GRCh38/hg38 12p13.33-13.32(chr12:80412-4420585)x1	Pathogenic
152450	GRCh38/hg38 12p13.33-13.32(chr12:54427-4004912)x1	Pathogenic
152732	GRCh38/hg38 12p13.33-13.32(chr12:54427-3639603)x1	Pathogenic
154528	GRCh38/hg38 12p13.33(chr12:121255-3003320)x1	Pathogenic
155290	GRCh38/hg38 12p13.33-13.31(chr12:418421-6235914)x3	Pathogenic
1809216	GRCh37/hg19 12p13.33(chr12:817514-2205439)x1	Pathogenic
253551	GRCh37/hg19 12p13.33-13.32(chr12:222888-3931052)x1	Pathogenic
2685429	GRCh37/hg19 12p13.33-13.32(chr12:191243-5332596)x1	Pathogenic
563979	GRCh37/hg19 12p13.33(chr12:173786-2793493)x1	Pathogenic
563982	GRCh37/hg19 12p13.33-13.32(chr12:173786-4105910)x1	Pathogenic
563985	GRCh37/hg19 12p13.33-13.31(chr12:173786-5952112)x1	Pathogenic
563986	GRCh37/hg19 12p13.33-13.31(chr12:173786-6039841)x1	Pathogenic
563987	GRCh37/hg19 12p13.33-13.31(chr12:173786-6201932)x1	Pathogenic
57044	GRCh38/hg38 12p13.33-13.32(chr12:121255-3968447)x1	Pathogenic
58952	GRCh38/hg38 12p13.33(chr12:99592-1786491)x1	Pathogenic
59798	GRCh38/hg38 12p13.33-13.32(chr12:199896-3284963)x3	Pathogenic
687115	GRCh37/hg19 12p13.33-13.31(chr12:173786-6346092)x1	Pathogenic
979958	GRCh37/hg19 12p13.33-13.32(chr12:191242-4683495)x1	Pathogenic
3024578	GRCh37/hg19 12p13.33(chr12:922808-2129821)x1	Likely pathogenic

SpliceAI

2425 predictions. Top by Δscore:

Variant	Effect	Δscore
12:1758457:G:GG	donor_gain	1.0000
12:1772838:GCAG:G	acceptor_loss	1.0000
12:1772839:CA:C	acceptor_loss	1.0000
12:1772839:CAG:C	acceptor_gain	1.0000
12:1772840:A:AC	acceptor_loss	1.0000
12:1772840:A:AG	acceptor_gain	1.0000
12:1772840:AGA:A	acceptor_gain	1.0000
12:1772841:G:GA	acceptor_gain	1.0000
12:1772841:GA:G	acceptor_gain	1.0000
12:1772841:GAG:G	acceptor_gain	1.0000
12:1772841:GAGC:G	acceptor_gain	1.0000
12:1772841:GAGCT:G	acceptor_gain	1.0000
12:1772957:GTAAG:G	donor_gain	1.0000
12:1772961:GGTAA:G	donor_loss	1.0000
12:1772963:T:A	donor_loss	1.0000
12:1780450:GGTT:G	acceptor_gain	1.0000
12:1783879:GGAGT:G	acceptor_gain	1.0000
12:1784069:TCTGG:T	donor_gain	1.0000
12:1784072:GG:G	donor_gain	1.0000
12:1784072:GGGTA:G	donor_loss	1.0000
12:1784073:GG:G	donor_gain	1.0000
12:1784074:G:GG	donor_gain	1.0000
12:1784074:GTAA:G	donor_loss	1.0000
12:1784075:T:G	donor_loss	1.0000
12:1757765:GCAGG:G	donor_gain	0.9900
12:1757768:GG:G	donor_gain	0.9900
12:1757769:GG:G	donor_gain	0.9900
12:1772828:T:TA	acceptor_gain	0.9900
12:1772832:T:TA	acceptor_gain	0.9900
12:1772944:G:GT	donor_gain	0.9900

AlphaMissense

2557 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:1777869:T:A	W103R	1.000
12:1777869:T:C	W103R	1.000
12:1777871:G:C	W103C	1.000
12:1777871:G:T	W103C	1.000
12:1777902:T:A	W114R	1.000
12:1777902:T:C	W114R	1.000
12:1777903:G:C	W114S	1.000
12:1777903:G:T	W114L	1.000
12:1777904:G:C	W114C	1.000
12:1777904:G:T	W114C	1.000
12:1777906:T:C	L115P	1.000
12:1777916:T:A	N118K	1.000
12:1777916:T:G	N118K	1.000
12:1777935:C:G	H125D	1.000
12:1777938:C:G	R126G	1.000
12:1777965:T:C	C135R	1.000
12:1777966:G:A	C135Y	1.000
12:1777966:G:T	C135F	1.000
12:1777967:T:G	C135W	1.000
12:1777974:A:C	S138R	1.000
12:1777976:C:A	S138R	1.000
12:1777976:C:G	S138R	1.000
12:1777996:A:T	E145V	1.000
12:1777997:A:C	E145D	1.000
12:1777997:A:T	E145D	1.000
12:1777999:C:T	T146I	1.000
12:1778006:C:A	N148K	1.000
12:1778006:C:G	N148K	1.000
12:1778010:T:A	W150R	1.000
12:1778010:T:C	W150R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005446 (12:1718374 G>A), RS1000038047 (12:1773540 A>G), RS1000057927 (12:1717902 A>G), RS1000096315 (12:1771394 A>C,G), RS1000103325 (12:1765769 G>A), RS1000143881 (12:1713281 A>G), RS1000144230 (12:1694619 A>C,G), RS1000172677 (12:1755230 CCACCA>C), RS1000184045 (12:1733759 C>T), RS1000241415 (12:1712194 A>C,G), RS1000243267 (12:1701622 T>C), RS1000338050 (12:1722866 T>C), RS1000378535 (12:1760645 G>A), RS1000380852 (12:1759563 C>A), RS1000402859 (12:1707796 A>G)

Disease associations

OMIM: gene MIM:607946 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001431_6	Adverse response to lamotrigine and phenytoin	3.000000e-06
GCST002830_34	Urate levels in lean individuals	5.000000e-06
GCST90002404_130	Red cell distribution width	7.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3392947 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Adiponectin receptors

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.51	Kd	3100	nM	CHEMBL3393145

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 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
2-(4-benzoylphenoxy)-N-(1-benzylpiperidin-4-yl)acetamide	1189230: Binding affinity to AdipoR2 (unknown origin) by surface plasmon resonance analysis	kd	3.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Progesterone	affects cotreatment, increases expression	2
MRI-1867	affects cotreatment, decreases expression, decreases reaction	1
parthenolide	affects binding, increases activity	1
taxifolin	affects binding, increases activity	1
bisphenol A	decreases methylation	1
trichostatin A	affects expression	1
osteum	decreases reaction, affects cotreatment, decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
schizandrin A	affects binding, increases activity	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
PCI 5002	affects cotreatment, increases expression	1
Rosiglitazone	decreases reaction, increases expression, increases activity, increases reaction	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	increases activity, increases reaction	1
Methotrexate	increases expression	1
Paraquat	decreases reaction, increases expression	1
Pesticides	decreases methylation	1
Phthalic Acids	decreases methylation	1
Piroxicam	decreases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3395076	Binding	Binding affinity to AdipoR2 (unknown origin) by surface plasmon resonance analysis	Small molecule adenosine 5’-monophosphate activated protein kinase (AMPK) modulators and human diseases. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3G1	HEK293T AdipoR2 KO	Transformed cell line	Female
CVCL_SB72	HAP1 ADIPOR2 (-) 1	Cancer cell line	Male
CVCL_XL12	HAP1 ADIPOR2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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