ADIPOR1

Summary

ADIPOR1 (adiponectin receptor 1, HGNC:24040) is a protein-coding gene on chromosome 1q32.1, encoding Adiponectin receptor protein 1 (Q96A54). Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism.

This gene encodes a protein which acts as a receptor for adiponectin, a hormone secreted by adipocytes which regulates fatty acid catabolism and glucose levels. Binding of adiponectin to the encoded protein results in activation of an AMP-activated kinase signaling pathway which affects levels of fatty acid oxidation and insulin sensitivity. A pseudogene of this gene is located on chromosome 14. Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 51094 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 220 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_015999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24040
Approved symbol	ADIPOR1
Name	adiponectin receptor 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	PAQR1, ACDCR1
Ensembl gene	ENSG00000159346
Ensembl biotype	protein_coding
OMIM	607945
Entrez	51094

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 27 protein_coding, 1 retained_intron

ENST00000340990, ENST00000367254, ENST00000417068, ENST00000426229, ENST00000495562, ENST00000855702, ENST00000855703, ENST00000855704, ENST00000855705, ENST00000855706, ENST00000855707, ENST00000855708, ENST00000855709, ENST00000855710, ENST00000940204, ENST00000940205, ENST00000940206, ENST00000940207, ENST00000940208, ENST00000940209, ENST00000942960, ENST00000942961, ENST00000942962, ENST00000942963, ENST00000942964, ENST00000942965, ENST00000942966, ENST00000942967

RefSeq mRNA: 4 — MANE Select: NM_015999 NM_001290553, NM_001290557, NM_001290629, NM_015999

CCDS: CCDS1430

Canonical transcript exons

ENST00000340990 — 8 exons

Exon	Start	End
ENSE00001044995	202946439	202946610
ENSE00001044996	202943758	202943945
ENSE00001044999	202948304	202948420
ENSE00001386121	202950930	202951164
ENSE00001653979	202958185	202958312
ENSE00001877687	202940832	202941701
ENSE00003649683	202942025	202942218
ENSE00003786628	202944983	202945169

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.6761 / max 2538.9895, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16757	49.0583	1821
16758	5.7169	1313
16756	1.1934	576
16755	0.7076	315

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.94	gold quality
monocyte	CL:0000576	98.12	gold quality
mononuclear cell	CL:0000842	98.11	gold quality
leukocyte	CL:0000738	97.97	gold quality
lower esophagus mucosa	UBERON:0035834	97.72	gold quality
skin of leg	UBERON:0001511	97.70	gold quality
bone marrow	UBERON:0002371	97.66	gold quality
skin of abdomen	UBERON:0001416	97.45	gold quality
islet of Langerhans	UBERON:0000006	97.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.28	gold quality
right lung	UBERON:0002167	97.12	gold quality
esophagus mucosa	UBERON:0002469	97.03	gold quality
minor salivary gland	UBERON:0001830	96.95	gold quality
saliva-secreting gland	UBERON:0001044	96.75	gold quality
zone of skin	UBERON:0000014	96.71	gold quality
upper lobe of left lung	UBERON:0008952	96.64	gold quality
upper lobe of lung	UBERON:0008948	96.42	gold quality
muscle of leg	UBERON:0001383	96.37	gold quality
mouth mucosa	UBERON:0003729	96.35	gold quality
gastrocnemius	UBERON:0001388	96.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.29	gold quality
bone marrow cell	CL:0002092	96.28	gold quality
body of pancreas	UBERON:0001150	96.21	gold quality
stromal cell of endometrium	CL:0002255	96.09	gold quality
pancreas	UBERON:0001264	95.95	gold quality
rectum	UBERON:0001052	95.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.77	gold quality
gall bladder	UBERON:0002110	95.58	gold quality
trabecular bone tissue	UBERON:0002483	95.57	gold quality
body of stomach	UBERON:0001161	95.56	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	184.57
E-MTAB-9221	yes	18.71
E-HCAD-9	yes	6.64
E-HCAD-10	yes	4.94
E-MTAB-9467	yes	4.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, ESR1, FOXO1

miRNA regulators (miRDB)

71 targeting ADIPOR1, 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-4455	100.00	65.48	1587
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4446-5P	99.72	69.19	2544

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 AdipoR1 as well as plasma adiponectin concentration were lower in people with a family history of Type 2. (PMID:15105989)
• ADIPOR1 mRNA levels were significantly lower among transformed lymphocytes from diabetic African-American individuals than among control cell lines. (PMID:15277397)
• 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 ADIPOR1 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 1 and type 2 diabetes among Amish. (PMID:15983228)
• AdipoR1 protein is neither altered by RXR or LXR agonists nor by pioglitazone. In contrast, fenofibric acid reduces AdipoR1 whereas hepatotoxic troglitazone upregulates AdipoR1 protein in HepG2 cells. (PMID:16023994)
• Skeletal musscle expression is independently and inversely correlated with measures of central obesity. (PMID:16043761)
• 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)
• the -8503 G/A single-nucleotide polymorphism in the promoter or the -1927 T/C single-nucleotide polymorphism in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans. (PMID:16205883)
• the A allele of the -8503 G/A SNP of the ADIPOR1 gene is associated with less insulin sensitivity only in more obese but not in lean individuals (PMID:16443913)
• adiponectin receptors have roles in the human endometrium (PMID:16601138)
• Adiponectin is an adipocyte-derived hormone that plays a critical role in the development of type 2 diabetes via interaction with adiponectin receptors 1. (PMID:16609881)
• APPL1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin. (PMID:16622416)
• 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)
• ADIPOR1 has a putative role in the development of body size, and traits for central adiposity and insulin resistance may be dissociated from each other. (PMID:16724230)
• adiponectin receptor-1 expression increased in adipose tissue of impaired glucose-tolerant obese subjects during weight loss (PMID:16793963)
• May contribute to the molecular association between obesity and prostate cancer through complex interaction with other hormones and cytokines that play important roles in the pathophysiology of obesity and prostate cancer. (PMID:16899222)
• Upregulated in insulin-resistant women with polycystic ovary syndrome. (PMID:17001470)
• Our findings point to genetic variability at the ADIPOR1 locus as a strong determinant of coronary artery disease susceptibility in type 2 diabetes. (PMID:17003341)
• 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 ADIPOR1is 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)
• Findings suggest that variant of ADIPOR1 plays a role in glucose metabolism and insulin resistance in the Chinese. (PMID:17285539)
• Significant associations between ADIPOR1 haplotypes and type 2 diabetes risk 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 AdipoR1. (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)
• Findings suggest not only that ADIPOR1 variants influence insulin resistance in the presence of adiposity, but also that these variants and haplotypes are protective in African Americans. (PMID:17712104)
• role of polymorphisms in the adiponectin receptor 1 and 2 genes (ADIPOR1 and ADIPOR2) in insulin resistance and type 2 diabetes [review] (PMID:17716299)
• Physical training for 4 weeks resulted in increased AdipoR1 and AdipoR2 mRNA expression in subcutaneous fat and may insulin resistance. (PMID:17878241)
• AdipoR1 receptor is involved in adiponectin-mediated increase of IL-6 production in synovial fibroblasts. (PMID:17911635)
• adiponectin decreases breast cancer cell proliferation by inhibiting the entry into S-phase without inducing apoptosis, and this inhibitory effect is mediated through adiponectin receptor 1 (PMID:18163210)
• Elevated ADIPOR1 expression is associated with colorectal carcinomas but not in gastrointestinal stromal tumors (PMID:18310295)
• Data show that globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation.( (PMID:18313838)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	adipor1a	ENSDARG00000002912
danio_rerio	adipor1b	ENSDARG00000042717
mus_musculus	Adipor1	ENSMUSG00000026457
rattus_norvegicus	Adipor1	ENSRNOG00000004143
drosophila_melanogaster	AdipoR	FBGN0038984
caenorhabditis_elegans		WBGENE00016610
caenorhabditis_elegans		WBGENE00019643

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Adiponectin receptor protein 1 — Q96A54 (reviewed: Q96A54)

Alternative names: Progestin and adipoQ receptor family member 1, Progestin and adipoQ receptor family member I

All UniProt accessions (4): Q96A54, C9J0W7, C9JNM5, F8W782

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 glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. Has high affinity for globular adiponectin and low affinity for full-length adiponectin.

Subunit / interactions. May form homooligomers and heterooligomers with ADIPOR2. Interacts with APPL2 (via BAR domain); hinders the accessibility of APPL1 to ADIPOR1; negatively regulates adiponectin signaling; ADIPOQ dissociates this interaction and facilitates the recruitment of APPL1 to ADIPOR1. Interacts with APPL1; ADIPOQ enhances this interaction; inhibits adiponectin-stimulated binding of APPL2 to ADIPOR1.

Subcellular location. Cell membrane.

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

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_001277482, NP_001277486, NP_001277558, NP_057083* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

UniProt features (52 total): helix 14, topological domain 8, transmembrane region 7, mutagenesis site 7, turn 6, binding site 3, strand 3, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5LXG	X-RAY DIFFRACTION	2.73
6KS0	X-RAY DIFFRACTION	2.79
6KRZ	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A54-F1	83.95	0.69

Antibody-complex structures (SAbDab): 3 — 5LXG, 6KRZ, 6KS0

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): 191; 337; 341

Mutagenesis-validated functional residues (7):

Position	Phenotype
161–167	decreases activation of ampk in response to adipoq binding; when associated with 229-g–g-231 and 291-s–s-297.
191	decreases activation of ampk in response to adipoq binding; when associated with a-208; a-337 and a-341.
208	decreases activation of ampk in response to adipoq binding; when associated with a-191; a-337 and a-341.
229–231	decreases activation of ampk in response to adipoq binding; when associated with 161-s–s-167 and 291-s–s-297.
291–297	decreases activation of ampk in response to adipoq binding; when associated with 161-s–s-167 and 229-g–g-231.
337	decreases activation of ampk in response to adipoq binding; when associated with a-191; a-208 and a-341.
341	decreases activation of ampk in response to adipoq binding; when associated with a-191; a-208 and a-337.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 235 (showing top): GOBP_LIPID_MODIFICATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_PEPTIDE, TTTGTAG_MIR520D, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_GROWTH, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CCATCCA_MIR432

GO Biological Process (17): hormone-mediated signaling pathway (GO:0009755), negative regulation of epithelial cell migration (GO:0010633), negative regulation of epithelial to mesenchymal transition (GO:0010719), regulation of glucose metabolic process (GO:0010906), regulation of lipid metabolic process (GO:0019216), fatty acid oxidation (GO:0019395), negative regulation of cell growth (GO:0030308), leptin-mediated signaling pathway (GO:0033210), adiponectin-activated signaling pathway (GO:0033211), glucose homeostasis (GO:0042593), negative regulation of receptor signaling pathway via JAK-STAT (GO:0046426), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), positive regulation of insulin receptor signaling pathway (GO:0046628), positive regulation of cold-induced thermogenesis (GO:0120162), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (7): protein kinase binding (GO:0019901), 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
negative regulation of multicellular organismal process	2
lipid metabolic process	2
cytokine-mediated signaling pathway	2
cell surface receptor signaling pathway via JAK-STAT	2
regulation of receptor signaling pathway via JAK-STAT	2
protein binding	2
signal transduction	1
cellular response to hormone stimulus	1
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
regulation of primary metabolic process	1
fatty acid metabolic process	1
lipid oxidation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cellular response to leptin stimulus	1
hormone-mediated signaling pathway	1
carbohydrate homeostasis	1
negative regulation of receptor signaling pathway via STAT	1
positive regulation of receptor signaling pathway via STAT	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
primary metabolic process	1

Protein interactions and networks

STRING

1434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADIPOR1	ADIPOQ	Q15848	999
ADIPOR1	APPL1	Q9UKG1	997
ADIPOR1	LEP	P41159	949
ADIPOR1	CDH13	P55290	904
ADIPOR1	ADIPOR2	Q86V24	885
ADIPOR1	IGF1R	P08069	877
ADIPOR1	PPARA	Q07869	853
ADIPOR1	SRC	P12931	837
ADIPOR1	INS	P01308	820
ADIPOR1	RETN	Q9HD89	794
ADIPOR1	NAMPT	P43490	780
ADIPOR1	PPARGC1A	Q9UBK2	737
ADIPOR1	RETNLB	Q9BQ08	737
ADIPOR1	PPARG	P37231	729
ADIPOR1	LEPR	P48357	725

IntAct

61 interactions, top by confidence:

A	B	Type	Score
ADIPOR1	TBXA2R	psi-mi:“MI:0915”(physical association)	0.560
TBXA2R	ADIPOR1	psi-mi:“MI:0915”(physical association)	0.560
APPL1	ADIPOR1	psi-mi:“MI:0915”(physical association)	0.550
APPL1	ADIPOR1	psi-mi:“MI:2364”(proximity)	0.550
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
ADIPOR1	WFS1	psi-mi:“MI:0914”(association)	0.530
ADIPOR1	ADIPOR1	psi-mi:“MI:0915”(physical association)	0.450
ADIPOR1	ADIPOR1	psi-mi:“MI:2364”(proximity)	0.450
Adipoq	ADIPOR1	psi-mi:“MI:0407”(direct interaction)	0.410
ADIPOR1	TLR4	psi-mi:“MI:0915”(physical association)	0.400
NFKBIL1	ADIPOR1	psi-mi:“MI:0915”(physical association)	0.370
ADIPOR1	NAA20	psi-mi:“MI:0915”(physical association)	0.370
ADIPOR1	DPH3	psi-mi:“MI:0915”(physical association)	0.370
ADIPOR1		psi-mi:“MI:0915”(physical association)	0.370
STK11	ADIPOR1	psi-mi:“MI:0915”(physical association)	0.370
RUSF1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
SLC18A1	LIMK2	psi-mi:“MI:0914”(association)	0.350
TACR1	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): ADIPOR1 (Affinity Capture-RNA), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Two-hybrid), ADIPOR1 (Proximity Label-MS), ADIPOR1 (Proximity Label-MS), FAM45A (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS), ADIPOR1 (Affinity Capture-MS)

ESM2 similar proteins: A2A559, A2V7M9, A6H7B8, A6X919, A7YWP2, A8KBG2, A8WFS8, B2GV22, D4AD75, E1BYA3, F1Q8R9, O08888, O45145, O49639, P25625, P38298, P70245, Q0VFE3, Q15125, Q290J8, Q2ABP2, Q2ABP3, Q3SZ36, Q3TQR0, Q568I2, Q5M9A7, Q60490, Q60WT2, Q68EV0, Q6P0S3, Q753H5, Q7K0P4, Q801D8, Q801G2, Q8C2R7, Q8N4S7, Q8R4X1, Q8T8L8, Q8TDN7, Q91VH1

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, Q6TCG2, Q6TCG5, Q6TCH4, Q6ZVX9, Q8N4S7, Q6DC77, Q9JJE4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ADIPOQ	up-regulates	ADIPOR1	binding
ADIPOR1	up-regulates	APPL1	binding
GRK2	“down-regulates activity”	ADIPOR1	phosphorylation
GRK2	“down-regulates quantity by destabilization”	ADIPOR1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	105
Likely benign	87
Benign	9

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1403201	NM_015999.6(ADIPOR1):c.929A>G (p.Tyr310Cys)	Pathogenic
58112	GRCh38/hg38 1q31.1-42.11(chr1:187143981-224299417)x3	Pathogenic
3062655	GRCh37/hg19 1q31.3-32.1(chr1:197216705-203683110)x1	Likely pathogenic
3062955	GRCh37/hg19 1q32.1(chr1:199373229-204335027)x3	Likely pathogenic

SpliceAI

1111 predictions. Top by Δscore:

Variant	Effect	Δscore
1:202941697:TGGAA:T	acceptor_gain	1.0000
1:202941698:GGAA:G	acceptor_gain	1.0000
1:202941699:GAA:G	acceptor_gain	1.0000
1:202941701:AC:A	acceptor_loss	1.0000
1:202941702:C:CC	acceptor_gain	1.0000
1:202941703:T:C	acceptor_loss	1.0000
1:202941704:G:C	acceptor_gain	1.0000
1:202942023:AC:A	donor_gain	1.0000
1:202942024:CC:C	donor_gain	1.0000
1:202942214:CACGC:C	acceptor_gain	1.0000
1:202942215:ACGC:A	acceptor_gain	1.0000
1:202942216:CGC:C	acceptor_gain	1.0000
1:202942216:CGCC:C	acceptor_gain	1.0000
1:202942217:GC:G	acceptor_gain	1.0000
1:202942218:CC:C	acceptor_gain	1.0000
1:202942219:C:CA	acceptor_loss	1.0000
1:202942219:C:CC	acceptor_gain	1.0000
1:202942219:C:T	acceptor_gain	1.0000
1:202942220:T:G	acceptor_loss	1.0000
1:202942224:C:CT	acceptor_gain	1.0000
1:202943753:CCTA:C	donor_loss	1.0000
1:202943754:CTA:C	donor_loss	1.0000
1:202948298:CCATA:C	donor_loss	1.0000
1:202948299:CATA:C	donor_loss	1.0000
1:202948300:ATACC:A	donor_loss	1.0000
1:202948301:TAC:T	donor_loss	1.0000
1:202948302:ACC:A	donor_loss	1.0000
1:202948303:C:CT	donor_loss	1.0000
1:202948303:CCTT:C	donor_gain	1.0000
1:202948417:CAGC:C	acceptor_gain	1.0000

AlphaMissense

2459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:202941678:A:C	H341Q	1.000
1:202941678:A:T	H341Q	1.000
1:202941680:G:C	H341D	1.000
1:202941680:G:T	H341N	1.000
1:202941690:A:C	H337Q	1.000
1:202941690:A:T	H337Q	1.000
1:202941692:G:C	H337D	1.000
1:202941694:G:A	S336F	1.000
1:202942086:C:T	G313E	1.000
1:202942087:C:G	G313R	1.000
1:202942087:C:T	G313R	1.000
1:202942211:G:C	F271L	1.000
1:202942211:G:T	F271L	1.000
1:202942213:A:G	F271L	1.000
1:202943762:T:A	R267S	1.000
1:202943762:T:G	R267S	1.000
1:202943826:C:T	G246D	1.000
1:202943827:C:G	G246R	1.000
1:202943906:G:C	S219R	1.000
1:202943906:G:T	S219R	1.000
1:202943908:T:G	S219R	1.000
1:202943911:C:G	G218R	1.000
1:202943911:C:T	G218R	1.000
1:202943919:A:G	L215P	1.000
1:202943928:A:T	I212N	1.000
1:202943931:C:A	G211V	1.000
1:202943931:C:T	G211E	1.000
1:202943932:C:A	G211W	1.000
1:202943932:C:G	G211R	1.000
1:202943932:C:T	G211R	1.000

dbSNP variants (sampled 300 via entrez): RS1000027834 (1:202942466 A>G), RS1000080392 (1:202944440 C>T), RS1000264710 (1:202950501 G>A), RS1000546318 (1:202941952 C>A,G), RS1000702391 (1:202955694 C>G,T), RS1000825332 (1:202948719 C>G,T), RS1000923124 (1:202955818 C>T), RS1000938620 (1:202955945 T>A), RS1000970598 (1:202943110 C>T), RS1001279796 (1:202956268 A>G), RS1001315990 (1:202950163 A>G), RS1001584464 (1:202943561 T>C), RS1001594291 (1:202952317 C>T), RS1001616900 (1:202956605 G>A), RS1001624973 (1:202958480 C>T)

Disease associations

OMIM: gene MIM:607945 | disease phenotypes: MIM:601887, MIM:170400, MIM:615400, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa	Moderate	Semidominant

Mondo (5): inherited retinal dystrophy (MONDO:0019118), malignant hyperthermia, susceptibility to, 5 (MONDO:0011163), hypokalemic periodic paralysis, type 1 (MONDO:0042979), epilepsy, familial adult myoclonic, 5 (MONDO:0014167), retinitis pigmentosa (MONDO:0019200)

Orphanet (5): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Malignant hyperthermia of anesthesia (Orphanet:423), Hypokalemic periodic paralysis (Orphanet:681), Familial adult myoclonic epilepsy (Orphanet:86814), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004599_260	Mean platelet volume	5.000000e-12
GCST90002395_549	Mean platelet volume	4.000000e-19

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C535698	Malignant hyperthermia susceptibility type 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3392946 (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
5.75	Kd	1800	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	1189229: Binding affinity to AdipoR1 (unknown origin) by surface plasmon resonance analysis	kd	1.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression	2
GSK-J4	increases expression	1
MRI-1867	decreases expression, decreases reaction, affects cotreatment	1
triphenyl phosphate	affects expression	1
fenofibric acid	decreases expression	1
gramine	affects binding, increases activity	1
25-hydroxycholesterol	affects cotreatment, decreases expression	1
terbufos	affects response to substance	1
osteum	affects cotreatment, decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
matairesinol	affects binding, increases activity	1
arctigenin	affects binding, increases activity	1
arctiin	affects binding, increases activity	1
CGP 52608	affects binding, increases reaction	1
Rosiglitazone	affects expression	1
Troglitazone	decreases expression	1
Alitretinoin	affects cotreatment, decreases expression	1
Acetaminophen	affects response to substance	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydralazine	increases expression, affects cotreatment	1
Lead	affects expression	1
Methotrexate	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
CHEMBL3395075	Binding	Binding affinity to AdipoR1 (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

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SB71	HAP1 ADIPOR1 (-) 1	Cancer cell line	Male
CVCL_XL09	HAP1 ADIPOR1 (-) 2	Cancer cell line	Male
CVCL_XL10	HAP1 ADIPOR1 (-) 3	Cancer cell line	Male
CVCL_XL11	HAP1 ADIPOR1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa