RBP4

Summary

RBP4 (retinol binding protein 4, HGNC:9922) is a protein-coding gene on chromosome 10q23.33, encoding Retinol-binding protein 4 (P02753). Retinol-binding protein that mediates retinol transport in blood plasma.

This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells.

Source: NCBI Gene 5950 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive retinal dystrophy due to retinol transport defect (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 199 total — 7 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006744

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9922
Approved symbol	RBP4
Name	retinol binding protein 4
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138207
Ensembl biotype	protein_coding
OMIM	180250
Entrez	5950

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 22 protein_coding

ENST00000371464, ENST00000371467, ENST00000371469, ENST00000854001, ENST00000854002, ENST00000854003, ENST00000854004, ENST00000854005, ENST00000854006, ENST00000854007, ENST00000854008, ENST00000854009, ENST00000854010, ENST00000854011, ENST00000854012, ENST00000854013, ENST00000854014, ENST00000854015, ENST00000854016, ENST00000854017, ENST00000854018, ENST00000960264

RefSeq mRNA: 3 — MANE Select: NM_006744 NM_001323517, NM_001323518, NM_006744

CCDS: CCDS31249, CCDS81488

Canonical transcript exons

ENST00000371464 — 6 exons

Exon	Start	End
ENSE00000932977	93593823	93594035
ENSE00000932979	93600667	93600803
ENSE00001455288	93601171	93601235
ENSE00001455290	93600918	93601046
ENSE00003391253	93600393	93600499
ENSE00003842579	93591694	93592112

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 87.3027 / max 17546.4812, expressed in 587 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110718	86.7109	580
110716	0.1908	45
110714	0.1746	69
110715	0.1654	63
110717	0.0610	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.94	gold quality
liver	UBERON:0002107	99.90	gold quality
type B pancreatic cell	CL:0000169	99.19	gold quality
islet of Langerhans	UBERON:0000006	98.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.52	gold quality
adipose tissue	UBERON:0001013	98.49	gold quality
pituitary gland	UBERON:0000007	98.47	gold quality
adenohypophysis	UBERON:0002196	97.96	gold quality
connective tissue	UBERON:0002384	97.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.64	gold quality
omental fat pad	UBERON:0010414	97.52	gold quality
skin of hip	UBERON:0001554	97.50	gold quality
peritoneum	UBERON:0002358	97.41	gold quality
tibia	UBERON:0000979	97.29	gold quality
synovial joint	UBERON:0002217	96.58	gold quality
decidua	UBERON:0002450	96.27	gold quality
cartilage tissue	UBERON:0002418	95.20	gold quality
nucleus accumbens	UBERON:0001882	94.23	gold quality
adult mammalian kidney	UBERON:0000082	93.77	gold quality
pericardium	UBERON:0002407	93.28	gold quality
caudate nucleus	UBERON:0001873	92.81	gold quality
prefrontal cortex	UBERON:0000451	92.72	gold quality
layer of synovial tissue	UBERON:0007616	92.52	gold quality
adult organism	UBERON:0007023	92.45	gold quality
tendon of biceps brachii	UBERON:0008188	92.30	gold quality
cingulate cortex	UBERON:0003027	92.27	gold quality
anterior cingulate cortex	UBERON:0009835	92.21	gold quality
nephron tubule	UBERON:0001231	92.09	gold quality
ascending aorta	UBERON:0001496	91.91	gold quality
right frontal lobe	UBERON:0002810	91.83	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	27541.73
E-MTAB-5061	yes	16525.49
E-MTAB-10553	yes	12480.81
E-HCAD-9	yes	9470.78
E-GEOD-81547	yes	4465.77
E-GEOD-81608	yes	2550.10
E-ENAD-27	yes	2174.01
E-GEOD-83139	yes	2154.47
E-GEOD-135922	yes	59.58
E-MTAB-6701	yes	16.39
E-MTAB-7303	no	858.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, HES1, HMGA1, NONO, NR5A1, NR5A2, PPARA, PPARG, RELA, SFPQ

miRNA regulators (miRDB)

17 targeting RBP4, 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-511-3P	99.99	68.85	1467
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646

Literature-anchored findings (GeneRIF, showing 40)

• Genetic variation in RBP4 is associated with amyloid polyneuropathy (PMID:15649951)
• generated models for the ensemble of conformers populated within this molten globule state; conformer changes give an opening of the retinol-binding site (PMID:16156801)
• Our findings point to profound differences between rodents and humans in the regulation of adipose or circulating RBP4 and challenge the notion that glucose uptake by adipocytes has a dominant role in the regulation of RBP4. (PMID:17003346)
• the rare alleles of four SNPs were associated with increased risk of diabetes (-803, G > A, P = 0.0054; +5169, C > T, P = 0.0025; +6969, G > C, P = 0.0015; +7542, T > del, P = 0.0015) (PMID:17006670)
• Plasma RBP4 concentrations were found to be elevated in subjects with impaired glucose tolerance or type 2 diabetes and to be related to various clinical parameters known to be associated with insulin resistance (PMID:17065684)
• Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. (PMID:17164313)
• a haplotype of 8 common SNPs in Caucasians was significantly increased in type 2 diabetics compared with controls (PMID:17174134)
• Circulating RBP4 is not associated with the amount of fat in liver, skin, viscera or muscles. (PMID:17259477)
• there is a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance (PMID:17299074)
• RBP4 is not a relevant systemic factor in the pathogenesis of insulin resistance in liver cirrhosis. (PMID:17337499)
• Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. (PMID:17405846)
• up-regulation of RBP4 mRNA in subcutaneous and omentum adipose tissue as well as isolated subcutaneous adipocytes of polycystic ovary syndrome women (PMID:17456573)
• Serum retinol binding protein 4 levels are significantly increased in polycystic ovary syndrome women and associated with insulin resistance. (PMID:17526940)
• RBP4 may contribute to the development of insulin resistance along with other adipokines (PMID:17550959)
• Plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. (PMID:17568782)
• RBP4 may be released from diabetic adipocytes and act locally to inhibit phosphorylation of IRS1 at serine (307), a phosphorylation site that may integrate nutrient sensing with insulin signaling (PMID:17575262)
• RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance (PMID:17595259)
• Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass (PMID:17618858)
• Markers of glucose and lipid metabolism were not independently related to serum RBP-4 in control subjects or chronic hemodialyis patients. (PMID:17630267)
• RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or coronary artery diseae. (PMID:17639305)
• Contribution of RBP4 from adipocytes to circulating adipokine levels should be evaluated in diabetic and obese patienets. (PMID:17661007)
• In obese men with metabolic syndrome, weight loss with a low-fat diet decreases the plasma LDL apoB-100 and HDL lipoprotein kinetics, involving changes in RBP4 levels. (PMID:17686833)
• Role of RBP4 genetic variation in susceptibility to type 2 diabetes and insulin resistance, possibly through an effect on RBP4 expression. (PMID:17728376)
• RBP4 may represent a link between visceral obesity and cardiovascular disease (PMID:17890490)
• Retinol binding protein 4 may contribute to the pathogenesis of nonalcoholic fatty liver disease in type 2 diabetics. (PMID:17904683)
• Serum RBP4 and TTR showed no differences between controls/type 1 diabetic children. (PMID:17957146)
• Report retinol-binding protein 4 expression in visceral and subcutaneous fat in human obesity. (PMID:18052678)
• RBP4 variation in the first month after RY-gastric bypass may be a predictor of weight loss success. (PMID:18081728)
• The associations of RBP4 with insulin sensitivity, percent trunk fat, and lipid levels are influenced by age (PMID:18239568)
• In fibroboasts, STRA6 transports retinol bidirectionally in an RBP4 dependent manner. (PMID:18316031)
• RBP4 level could be used as an index of cardiovascular disease risk in subclinical hypothyroidism. (PMID:18381580)
• RBP4 is not a useful marker of insulin resistance in polycystic ovary syndrome but may reflect other metabolic features of this condition. (PMID:18390799)
• RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses. (PMID:18397979)
• Data show that increase in RBP4 from early to late pregnancy, associated with a decline in insulin sensitivity, potentially indicates interactions with glucose metabolism. (PMID:18426814)
• Neither retinol nor RBP-4 were associated with peak bone mineral density in young men (PMID:18426837)
• Relationship between circulating RBP4 and iron stores, both cross-sectional and after iron depletion, and in vitro findings suggest that iron could play a role in the RBP4-insulin resistance relationship. (PMID:18426863)
• RBP4 measured by two different techniques is not elevated, but the RBP4:retinol molar ratio is higher and correlates with fasting blood glucose in women with gestational diabetes (PMID:18437353)
• Although associated with visceral fat, serum RBP4 and adiponectin levels do not play important, fat-mass-independent primary roles in the development of PCOS. (PMID:18445670)
• RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine (PMID:18466349)
• The severity of glucose intolerance in women with previous gestational diabetes mellitus is associated with high RBP4 and low adiponectin concentrations. (PMID:18492757)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbp4	ENSDARG00000101199
mus_musculus	Rbp4	ENSMUSG00000024990
rattus_norvegicus	Rbp4	ENSRNOG00000015518

Protein

Protein identifiers

Retinol-binding protein 4 — P02753 (reviewed: P02753)

Alternative names: Plasma retinol-binding protein

All UniProt accessions (2): P02753, Q5VY30

UniProt curated annotations — full annotation on UniProt →

Function. Retinol-binding protein that mediates retinol transport in blood plasma. Delivers retinol from the liver stores to the peripheral tissues. Transfers the bound all-trans retinol to STRA6, that then facilitates retinol transport across the cell membrane.

Subunit / interactions. Interacts with TTR. Interaction with TTR prevents its loss by filtration through the kidney glomeruli. Interacts with STRA6.

Subcellular location. Secreted.

Tissue specificity. Detected in blood plasma and in urine (at protein level).

Disease relevance. Retinal dystrophy, iris coloboma, and comedogenic acne syndrome (RDCCAS) [MIM:615147] A disease characterized by retinal degeneration, ocular colobomas involving both the anterior and posterior segment, impaired night vision and loss of visual acuity. Additional characteristic features include developmental abnormalities and severe acne. The disease is caused by variants affecting the gene represented in this entry. Loss of functional RBP4 protein results in serum retinol deficiency. Lack of normal levels of retinol impairs the visual cycle leading to night blindness at early stages; prolonged deficiency may lead to retinal degeneration. Additionally, retinol deficiency may result in dry skin, increased susceptibility to infection and acne. Microphthalmia/Coloboma 10 (MCOPCB10) [MIM:616428] A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the calycin superfamily. Lipocalin family.

RefSeq proteins (3): NP_001310446, NP_001310447, NP_006735* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000566	Lipocln_cytosolic_FA-bd_dom	Domain
IPR002449	Retinol-bd/Purpurin	Family
IPR012674	Calycin	Homologous_superfamily
IPR022271	Lipocalin_ApoD	Family
IPR022272	Lipocalin_CS	Conserved_site

Pfam: PF00061

UniProt features (33 total): strand 10, chain 5, sequence variant 4, disulfide bond 3, helix 3, turn 3, sequence conflict 2, signal peptide 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
5NU2	X-RAY DIFFRACTION	1.5
5NU7	X-RAY DIFFRACTION	1.5
5NU9	X-RAY DIFFRACTION	1.5
5NU8	X-RAY DIFFRACTION	1.59
5NUA	X-RAY DIFFRACTION	1.6
5NUB	X-RAY DIFFRACTION	1.6
2WQ9	X-RAY DIFFRACTION	1.65
5NU6	X-RAY DIFFRACTION	1.68
1JYD	X-RAY DIFFRACTION	1.7
2WR6	X-RAY DIFFRACTION	1.8
6QBA	X-RAY DIFFRACTION	1.8
1JYJ	X-RAY DIFFRACTION	2
1RBP	X-RAY DIFFRACTION	2
5NTY	X-RAY DIFFRACTION	2
4O9S	X-RAY DIFFRACTION	2.3
4PSQ	X-RAY DIFFRACTION	2.4
1BRP	X-RAY DIFFRACTION	2.5
1BRQ	X-RAY DIFFRACTION	2.5
2WQA	X-RAY DIFFRACTION	2.85
3FMZ	X-RAY DIFFRACTION	2.9
1RLB	X-RAY DIFFRACTION	3.1
1QAB	X-RAY DIFFRACTION	3.2
3BSZ	X-RAY DIFFRACTION	3.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02753-F1	90.33	0.79

Antibody-complex structures (SAbDab): 1 — 3BSZ

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 (1): 116

Post-translational modifications (1): 139

Disulfide bonds (3): 138–147, 22–178, 88–192

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-6809583	Retinoid metabolism disease events
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9918449	Defective visual phototransduction due to STRA6 loss of function

MSigDB gene sets: 410 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_DIGESTION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AP1_01, GOBP_RESPONSE_TO_ETHANOL, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, PAX4_01, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GNF2_GSTM1, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (34): eye development (GO:0001654), positive regulation of immunoglobulin production (GO:0002639), gluconeogenesis (GO:0006094), spermatogenesis (GO:0007283), heart development (GO:0007507), phototransduction, visible light (GO:0007603), male gonad development (GO:0008584), response to xenobiotic stimulus (GO:0009410), response to muscle activity (GO:0014850), maintenance of gastrointestinal epithelium (GO:0030277), lung development (GO:0030324), positive regulation of insulin secretion (GO:0032024), response to retinoic acid (GO:0032526), response to insulin (GO:0032868), retinol transport (GO:0034633), retinol metabolic process (GO:0042572), retinal metabolic process (GO:0042574), glucose homeostasis (GO:0042593), response to ethanol (GO:0045471), embryonic organ morphogenesis (GO:0048562), embryonic skeletal system development (GO:0048706), cardiac muscle tissue development (GO:0048738), female genitalia morphogenesis (GO:0048807), detection of light stimulus involved in visual perception (GO:0050908), negative regulation of cardiac muscle cell proliferation (GO:0060044), embryonic retina morphogenesis in camera-type eye (GO:0060059), uterus development (GO:0060065), vagina development (GO:0060068), urinary bladder development (GO:0060157), heart trabecula formation (GO:0060347), vitamin A import into cell (GO:0071939), retinoid metabolic process (GO:0001523), visual perception (GO:0007601), retina development in camera-type eye (GO:0060041)

GO Molecular Function (7): retinal binding (GO:0016918), retinol binding (GO:0019841), retinol transmembrane transporter activity (GO:0034632), protein-containing complex binding (GO:0044877), molecular carrier activity (GO:0140104), retinoid binding (GO:0005501), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Visual phototransduction	2
Diseases associated with visual transduction	1
Metabolism of fat-soluble vitamins	1
Retinoid cycle disease events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
animal organ development	2
retinoid metabolic process	2
olefinic compound metabolic process	2
retinoid binding	2
vitamin binding	2
sensory organ development	1
visual system development	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
glucose metabolic process	1
hexose biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
circulatory system development	1
phototransduction	1
detection of visible light	1
gonad development	1
development of primary male sexual characteristics	1
response to chemical	1
response to activity	1
epithelial structure maintenance	1
digestive system process	1
respiratory tube development	1
respiratory system development	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
response to lipid	1
response to oxygen-containing compound	1
response to peptide hormone	1
organic hydroxy compound transport	1
terpenoid transport	1
primary alcohol metabolic process	1
hormone metabolic process	1
aldehyde metabolic process	1
carbohydrate homeostasis	1
response to alcohol	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBP4	TTR	P02766	997
RBP4	STRA6	Q9BX79	993
RBP4	RBP1	P09455	820
RBP4	ADIPOQ	Q15848	771
RBP4	CRP	P02741	768
RBP4	APCS	P02743	768
RBP4	RETN	Q9HD89	763
RBP4	BCO1	Q9HAY6	750
RBP4	APOA1	P02647	745
RBP4	RETNLB	Q9BQ08	728
RBP4	SLC2A4	P14672	719
RBP4	LEP	P41159	714
RBP4	AZGP1	P25311	713
RBP4	CYP2C18	P33260	712
RBP4	NAMPT	P43490	695

IntAct

30 interactions, top by confidence:

A	B	Type	Score
TRADD	TNF	psi-mi:“MI:0914”(association)	0.790
RBP4	TTR	psi-mi:“MI:2364”(proximity)	0.650
RBP4	TTR	psi-mi:“MI:0915”(physical association)	0.650
TTR	RBP4	psi-mi:“MI:0407”(direct interaction)	0.650
HESX1	RBP4	psi-mi:“MI:0915”(physical association)	0.560
HESX1	RBP4	psi-mi:“MI:0914”(association)	0.560
RBP4	TTR	psi-mi:“MI:0407”(direct interaction)	0.560
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
MARCKSL1	NMT2	psi-mi:“MI:0914”(association)	0.530
TMEM205	RBP4	psi-mi:“MI:0914”(association)	0.530
RBP4	POLR3D	psi-mi:“MI:0914”(association)	0.530
CRYBA4	RBP4	psi-mi:“MI:0914”(association)	0.530
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
RBP4		psi-mi:“MI:0915”(physical association)	0.370
CRYBA4	APAF1	psi-mi:“MI:0914”(association)	0.350
MSRB3	SPOP	psi-mi:“MI:0914”(association)	0.350
TMEM223	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
SNX21	RBP4	psi-mi:“MI:0914”(association)	0.350
UBE2U	IGLL5	psi-mi:“MI:0914”(association)	0.350
RBP4	POLR3A	psi-mi:“MI:0914”(association)	0.350
GRB2	RBP4	psi-mi:“MI:0915”(physical association)	0.000
RIPPLY3	RBP4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): RBP4 (Two-hybrid), RBP4 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), MTO1 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), POLR3D (Affinity Capture-MS), KLHL24 (Affinity Capture-MS), RBP4 (Affinity Capture-Luminescence), RBP4 (FRET), TTR (Affinity Capture-Luminescence), RBP4 (Affinity Capture-MS), RBP4 (Co-purification)

ESM2 similar proteins: A2AEP0, A2AJB7, M5AXY1, O18874, O95445, P00978, P02753, P02763, P02764, P04916, P04939, P06910, P06911, P06912, P07361, P09465, P11944, P14630, P19652, P21350, P21352, P21760, P27485, P35578, P36992, P41263, P61641, P81608, Q00724, Q07456, Q28369, Q28388, Q29147, Q29614, Q2LE37, Q3SZR3, Q5R894, Q5VFH6, Q60559, Q60590

Diamond homologs: M5AXY1, P02753, P04916, P05090, P06172, P06912, P08938, P18902, P24774, P24775, P27485, P41263, P51909, P61641, Q00724, Q28369, Q8SPI0, P37153, Q32KY0, P00305, P09464, P0A901, P0A902, P23593, P51910, Q00630, Q46036, Q5ECE3, Q5URA7, Q9FGT8, Q9STS7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RBP4	“up-regulates quantity”	retinol	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	12
Uncertain significance	95
Likely benign	64
Benign	17

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1453574	NM_006744.4(RBP4):c.67C>T (p.Arg23Ter)	Pathogenic
1920770	NM_006744.4(RBP4):c.111+1G>C	Pathogenic
192377	NM_006744.4(RBP4):c.217G>A (p.Ala73Thr)	Pathogenic
2125118	NM_006744.4(RBP4):c.324_349del (p.Tyr108_Lys117delinsTer)	Pathogenic
41423	NM_006744.4(RBP4):c.111+1G>A	Pathogenic
961911	NM_006744.4(RBP4):c.129C>G (p.Tyr43Ter)	Pathogenic
976725	NM_006744.4(RBP4):c.526G>T (p.Glu176Ter)	Pathogenic
13068	NM_006744.4(RBP4):c.278G>A (p.Gly93Asp)	Likely pathogenic
1465487	NM_006744.4(RBP4):c.244_248+2del	Likely pathogenic
192376	NM_006744.4(RBP4):c.223G>A (p.Ala75Thr)	Likely pathogenic
2130363	NM_006744.4(RBP4):c.355+1G>A	Likely pathogenic
2430196	NM_006744.4(RBP4):c.218C>T (p.Ala73Val)	Likely pathogenic
2430197	NM_006744.4(RBP4):c.358G>T (p.Asp120Tyr)	Likely pathogenic
2430199	NM_006744.4(RBP4):c.383A>G (p.Asp128Gly)	Likely pathogenic
2430200	NM_006744.4(RBP4):c.358G>C (p.Asp120His)	Likely pathogenic
3249265	NM_006744.4(RBP4):c.38_56del (p.Leu13fs)	Likely pathogenic
438114	NM_006744.4(RBP4):c.248+1G>A	Likely pathogenic
493081	NM_006744.4(RBP4):c.353G>A (p.Gly118Glu)	Likely pathogenic
929566	NM_006744.4(RBP4):c.569-1G>A	Likely pathogenic

SpliceAI

724 predictions. Top by Δscore:

Variant	Effect	Δscore
10:93593819:TCA:T	donor_loss	1.0000
10:93593820:CA:C	donor_loss	1.0000
10:93593821:A:AC	donor_gain	1.0000
10:93593821:A:AG	donor_loss	1.0000
10:93593822:C:CC	donor_gain	1.0000
10:93594036:C:CC	acceptor_gain	1.0000
10:93600387:ACT:A	donor_loss	1.0000
10:93600388:CTC:C	donor_loss	1.0000
10:93600389:TCA:T	donor_loss	1.0000
10:93600390:CAC:C	donor_loss	1.0000
10:93600391:A:AC	donor_gain	1.0000
10:93600391:ACTT:A	donor_gain	1.0000
10:93600391:ACTTC:A	donor_gain	1.0000
10:93600392:C:CT	donor_gain	1.0000
10:93600392:C:G	donor_loss	1.0000
10:93600392:CT:C	donor_gain	1.0000
10:93600392:CTT:C	donor_gain	1.0000
10:93600392:CTTC:C	donor_gain	1.0000
10:93600392:CTTCC:C	donor_gain	1.0000
10:93600394:T:TA	donor_gain	1.0000
10:93600395:C:A	donor_gain	1.0000
10:93600429:T:TA	donor_gain	1.0000
10:93600497:TTA:T	acceptor_gain	1.0000
10:93600498:TA:T	acceptor_gain	1.0000
10:93600500:C:CC	acceptor_gain	1.0000
10:93600577:C:A	donor_gain	1.0000
10:93600665:A:AC	donor_gain	1.0000
10:93600666:C:CC	donor_gain	1.0000
10:93600666:CTT:C	donor_gain	1.0000
10:93600668:T:TA	donor_gain	1.0000

AlphaMissense

1329 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:93593978:C:G	C138S	0.999
10:93593979:A:T	C138S	0.999
10:93600789:C:A	W42C	0.999
10:93600789:C:G	W42C	0.999
10:93600791:A:G	W42R	0.999
10:93600791:A:T	W42R	0.999
10:93593950:A:C	C147W	0.998
10:93593951:C:G	C147S	0.998
10:93593951:C:T	C147Y	0.998
10:93593952:A:G	C147R	0.998
10:93593952:A:T	C147S	0.998
10:93593977:G:C	C138W	0.998
10:93593978:C:T	C138Y	0.998
10:93593979:A:G	C138R	0.998
10:93593994:C:G	A133P	0.998
10:93600425:T:C	Y108C	0.998
10:93600426:A:G	Y108H	0.998
10:93600686:C:G	G77R	0.998
10:93600754:A:C	F54C	0.998
10:93600774:C:A	K47N	0.998
10:93600774:C:G	K47N	0.998
10:93593937:A:G	S152P	0.997
10:93593978:C:A	C138F	0.997
10:93593985:A:C	Y136D	0.997
10:93593993:G:T	A133D	0.997
10:93600485:C:G	C88S	0.997
10:93600486:A:T	C88S	0.997
10:93600697:G:T	A73D	0.997
10:93600727:A:G	F63S	0.997
10:93600779:C:G	A46P	0.997

dbSNP variants (sampled 300 via entrez): RS1000096870 (10:93592325 G>A,T), RS1000624432 (10:93602599 T>C), RS1001108263 (10:93598421 G>C), RS1001736132 (10:93598314 C>T), RS1001843192 (10:93602859 T>C), RS1001881126 (10:93602630 C>G), RS1002069605 (10:93596902 T>C), RS1002149864 (10:93603635 T>C,G), RS1002627645 (10:93599953 C>T), RS1003118378 (10:93601188 C>A,G,T), RS1003356448 (10:93596359 C>A), RS1003437647 (10:93602507 C>A,G), RS1003652003 (10:93593643 T>C), RS1003880819 (10:93603229 A>C), RS1003996816 (10:93602874 C>A,T)

Disease associations

OMIM: gene MIM:180250 | disease phenotypes: MIM:615147, MIM:616428, MIM:107250

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive retinal dystrophy due to retinol transport defect	Definitive	Autosomal recessive
microphthalmia, isolated, with coloboma 10	Strong	Autosomal dominant
microphthalmia, isolated, with coloboma	Strong	Autosomal dominant
isolated anophthalmia-microphthalmia syndrome	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive retinal dystrophy due to retinol transport defect	Definitive	AR

Mondo (8): progressive retinal dystrophy due to retinol transport defect (MONDO:0014060), microphthalmia, isolated, with coloboma 10 (MONDO:0014635), microphthalmia (MONDO:0021129), anterior segment dysgenesis (MONDO:0019503), coloboma (MONDO:0001476), inherited retinal dystrophy (MONDO:0019118), isolated anophthalmia-microphthalmia syndrome (MONDO:0016764), microphthalmia, isolated, with coloboma (MONDO:0000170)

Orphanet (5): Progressive retinal dystrophy due to retinol transport defect (Orphanet:352718), Colobomatous microphthalmia (Orphanet:98938), Anterior segment developmental anomaly (Orphanet:88632), OBSOLETE: Ocular coloboma (Orphanet:194), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000482	Microcornea
HP:0000505	Visual impairment
HP:0000528	Anophthalmia
HP:0000552	Tritanomaly
HP:0000556	Retinal dystrophy
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000612	Iris coloboma
HP:0000662	Nyctalopia
HP:0001643	Patent ductus arteriosus
HP:0007502	Follicular hyperkeratosis
HP:0007663	Reduced visual acuity
HP:0011463	Childhood onset
HP:0025492	Microcoria
HP:0030825	Absent foveal reflex
HP:0031032	Decreased circulating retinol-binding protein concentration
HP:0034567	Optic pit
HP:0040137	Comedonal acne
HP:0200070	Peripheral retinal atrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001216_1	Retinol levels	7.000000e-15
GCST006585_2234	Blood protein levels	7.000000e-09
GCST006585_2484	Blood protein levels	1.000000e-07
GCST009411_9	Optic disc area	4.000000e-08

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D008850	Microphthalmos	C11.250.566; C16.131.384.666
D058499	Retinal Dystrophies	C11.768.585.658
C537463	Microphthalmia associated with colobomatous cyst (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3100 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 301,602 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL986	RETINOL	4	277,603
CHEMBL3967849	TINLAREBANT	3	64
CHEMBL7301	FENRETINIDE	3	23,935

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Fatty acid-binding proteins

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

Ligand	Action	Affinity	Parameter
tinlarebant	Inhibition	8.35	pIC50
A1120	Inhibition	7.85	pIC50

Binding affinities (BindingDB)

144 measured of 144 human assays (144 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carbonitrile	IC50	1.62 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-tert-butylphenyl)piperazin-1-yl]-(1H-imidazol-5-yl)methanone	IC50	3.8 nM	US-8853215: Derivatives of N-acyl-N′-phenylpiperazine useful (inter alia) for the prophylaxis or treatment of diabetes
[6-(cyclopropylmethyl)-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-3-yl]-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	IC50	4.35 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-tert-butylphenoxy)piperidin-1-yl]-pyridin-2-ylmethanone	IC50	5 nM	US-8586571: Heterocyclic compound
3-[4-(2-chloro-3-fluorophenyl)piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carbonitrile	IC50	5.12 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[2-fluoro-6-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	IC50	5.84 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-chloro-5-fluorophenyl)piperidin-1-yl]-(5-methylsulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl)methanone	IC50	6.17 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-N-methyl-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carboxamide	IC50	7.5 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[3-(2-tert-butylphenyl)sulfanylazetidin-1-yl]-pyridin-2-ylmethanone	IC50	10 nM	US-8586571: Heterocyclic compound
[5-(cyclopropylmethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	IC50	10 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
methyl 3-[4-[3,5-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylate	IC50	10.1 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-N-methyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxamide	IC50	10.2 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-chloro-3-fluorophenyl)piperidin-1-yl]-(5-methylsulfonyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl)methanone	IC50	10.3 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-N-methyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxamide	IC50	10.3 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3,5-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	IC50	10.5 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[6-(2-methoxyethyl)-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-3-yl]methanone	IC50	10.6 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3-chloro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	IC50	10.7 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[6-(3,3,3-trifluoropropyl)-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-3-yl]methanone	IC50	10.7 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(3,3,3-trifluoropropyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	10.8 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-(4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)methanone	IC50	10.9 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
1-[3-[4-[3,5-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-6-yl]ethanone	IC50	10.9 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(pyridine-4-carbonyl)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]methanone	IC50	11.2 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
methyl 3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carboxylate	IC50	11.4 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-N-methyl-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carboxamide	IC50	11.5 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(oxetan-3-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	11.6 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
1-[3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanone	IC50	11.6 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
1-[3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-5-yl]ethanone	IC50	11.6 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-chloro-3-fluorophenyl)piperidin-1-yl]-[5-(3,3,3-trifluoropropyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	11.7 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(oxetan-3-yl)-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]methanone	IC50	11.8 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
2-[3-[(2-tert-butyl-4-chlorophenoxy)methyl]azetidin-1-yl]-2-oxoacetic acid	IC50	12 nM	US-8586571: Heterocyclic compound
3-[4-[3,5-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carbonitrile	IC50	12 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-chloro-3-fluorophenyl)piperidin-1-yl]-[5-(2,2,2-trifluoroethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	12.2 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-(5-ethyl-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl)methanone	IC50	12.7 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
3-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	IC50	12.7 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
methyl 3-[4-[3,5-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridine-6-carboxylate	IC50	12.8 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-(4,5,6,7-tetrahydro-1H-pyrazolo[5,4-c]pyridin-3-yl)methanone	IC50	13.3 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[5-(cyclopropylmethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	IC50	13.4 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-chloro-3-fluorophenyl)piperidin-1-yl]-[5-(cyclopropylmethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	13.6 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,5-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(3,3,3-trifluoropropyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	13.8 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
1-[3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-6-yl]ethanone	IC50	13.9 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-(2-chloro-3-fluorophenyl)piperidin-1-yl]-(4,5,6,7-tetrahydro-1H-pyrazolo[5,4-c]pyridin-3-yl)methanone	IC50	14 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
methyl 3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazole-5-carboxylate	IC50	14.1 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[6-(cyclopropylmethyl)-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-3-yl]-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	IC50	14.2 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[5-(cyclopropylmethyl)-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	IC50	14.3 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(2,2-dimethylpropyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]methanone	IC50	14.4 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[6-(2-methoxyethyl)-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-3-yl]methanone	IC50	14.6 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
1-[3-[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-5-yl]propan-1-one	IC50	14.7 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[5-(2-methoxyethyl)-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]methanone	IC50	14.9 nM	US-10072016: Substituted 4-phenylpiperidines, their preparation and use
[4-[3,4-difluoro-2-(trifluoromethyl)phenyl]piperidin-1-yl]-[6-(2,2,2-trifluoroethyl)-1,4,5,7-tetrahydropyrazolo[5,4-c]pyridin-3-yl]methanone	IC50	15 nM	US-9434727: Substituted 4-phenylpiperidines, their preparation and use
[3-(2-tert-butyl-4-chlorophenoxy)azetidin-1-yl]-pyridin-2-ylmethanone	IC50	15 nM	US-8586571: Heterocyclic compound

ChEMBL bioactivities

1278 potent at pChembl≥5 of 1282 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	IC50	0.121	nM	CHEMBL3359024
9.81	IC50	0.155	nM	CHEMBL1230001
9.75	IC50	0.179	nM	CHEMBL3359022
9.63	IC50	0.235	nM	CHEMBL3359023
9.54	IC50	0.285	nM	CHEMBL3359017
9.53	IC50	0.294	nM	CHEMBL3359014
9.47	IC50	0.34	nM	CHEMBL3359019
9.32	IC50	0.481	nM	CHEMBL3359015
9.26	IC50	0.554	nM	CHEMBL3359005
9.08	IC50	0.829	nM	CHEMBL3359028
8.81	IC50	1.55	nM	CHEMBL3359020
8.79	IC50	1.619	nM	CHEMBL3983972
8.79	IC50	1.62	nM	CHEMBL3929712
8.78	IC50	1.68	nM	CHEMBL5949367
8.58	IC50	2.65	nM	CHEMBL3358470
8.57	IC50	2.7	nM	CHEMBL4472596
8.57	IC50	2.66	nM	CHEMBL4462481
8.55	IC50	2.824	nM	TINLAREBANT
8.54	IC50	2.88	nM	CHEMBL3983972
8.54	IC50	2.88	nM	CHEMBL3929712
8.52	IC50	3	nM	CHEMBL3288340
8.51	IC50	3.104	nM	CHEMBL3961492
8.51	IC50	3.1	nM	CHEMBL3961492
8.50	IC50	3.13	nM	CHEMBL3358466
8.48	IC50	3.3	nM	CHEMBL3593524
8.47	IC50	3.4	nM	CHEMBL4546092
8.46	IC50	3.447	nM	CHEMBL3890586
8.46	IC50	3.45	nM	CHEMBL3890586
8.44	IC50	3.6	nM	CHEMBL4469381
8.43	IC50	3.71	nM	CHEMBL4532832
8.43	IC50	3.7	nM	CHEMBL4452483
8.43	IC50	3.75	nM	CHEMBL4468564
8.42	IC50	3.8	nM	CHEMBL3644466
8.41	IC50	3.9	nM	CHEMBL3594229
8.41	IC50	3.9	nM	CHEMBL4524379
8.40	IC50	3.94	nM	CHEMBL3358465
8.40	IC50	4.01	nM	CHEMBL4457361
8.40	IC50	3.97	nM	CHEMBL4570619
8.39	IC50	4.1	nM	CHEMBL3594225
8.39	IC50	4.1	nM	CHEMBL4559814
8.38	IC50	4.128	nM	CHEMBL3954871
8.38	IC50	4.12	nM	CHEMBL4514302
8.38	IC50	4.13	nM	CHEMBL3954871
8.36	IC50	4.345	nM	CHEMBL3964999
8.36	IC50	4.329	nM	TINLAREBANT
8.36	IC50	4.35	nM	CHEMBL3964999
8.36	IC50	4.33	nM	TINLAREBANT
8.35	IC50	4.457	nM	CHEMBL3892353
8.35	IC50	4.5	nM	CHEMBL4586625
8.35	IC50	4.46	nM	CHEMBL3892353

PubChem BioAssay actives

274 with measured affinity, of 447 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.

Compound	Assay	Type	Value	Unit
5-[[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]pyridazine-4-carboxylic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0001	uM
4-[[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]-6-methylpyridine-3-carboxylic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0002	uM
2-[[4-[2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]amino]benzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0002	uM
4-[[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]pyridine-3-carboxylic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0002	uM
2-[[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]benzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0003	uM
2-[[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]-5-fluorobenzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0003	uM
2-[[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]-5-chlorobenzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0003	uM
2-[[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,6,6a-tetrahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]benzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0005	uM
2-[[2-(2-tert-butylphenoxy)ethyl-methylcarbamoyl]amino]benzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0006	uM
(2S)-2-[[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]-2-phenylacetic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0008	uM
2-[[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]-5-methylsulfonylbenzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0015	uM
(6-methylimidazo[1,2-b]pyridazin-2-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0027	uM
2-[[methyl-[2-[2-(trifluoromethyl)phenoxy]ethyl]carbamoyl]amino]benzoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0027	uM
[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-(6-ethoxy-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0027	uM
1,3-thiazol-2-yl-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1153659: Inhibition of human recombinant RBP4-transthyretin interaction by FRET analysis	ic50	0.0030	uM
2-oxo-2-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]acetic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0031	uM
2-[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-6-methylpyrimidine-4-carboxamide	1235542: Displacement of [3H]-retinol from RBP4 (unknown origin) by scintillation proximity assay	ic50	0.0033	uM
[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-[6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0034	uM
(6-cyclopropylimidazo[1,2-b]pyridazin-2-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0036	uM
[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]-[6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0037	uM
(6-methoxy-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0037	uM
(1-methylindazol-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0037	uM
N-[2-(benzenesulfonylcarbamoyl)phenyl]-4-[2-(trifluoromethyl)phenyl]piperidine-1-carboxamide	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0039	uM
(6-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0039	uM
methyl 2-[(3aS,6aR)-2-[2-(trifluoromethyl)phenyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-6-methylpyrimidine-4-carboxylate	1235542: Displacement of [3H]-retinol from RBP4 (unknown origin) by scintillation proximity assay	ic50	0.0039	uM
(6-ethoxy-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0040	uM
(6-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0040	uM
methyl 6-methyl-2-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]pyrimidine-4-carboxylate	1235542: Displacement of [3H]-retinol from RBP4 (unknown origin) by scintillation proximity assay	ic50	0.0041	uM
[6-fluoro-1-(oxetan-3-yl)indazol-3-yl]-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0041	uM
[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-(6-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0041	uM
[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-(6-chloro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0045	uM
(6-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0046	uM
(6-fluoro-1H-indazol-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0047	uM
(5-fluoro-1H-indazol-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0047	uM
3-[4-[5-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0049	uM
imidazo[1,2-b]pyridazin-2-yl-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0050	uM
3-[4-[2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0051	uM
N-[2-(cyclopropylsulfonylcarbamoyl)phenyl]-4-[2-(trifluoromethyl)phenyl]piperidine-1-carboxamide	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0053	uM
(2S)-2-[[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]amino]propanoic acid	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0053	uM
(7-chloro-2H-indazol-3-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0055	uM
3-[4-[3-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0057	uM
3-[4-[2-fluoro-6-(trifluoromethyl)phenyl]piperidine-1-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0058	uM
[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-(6-methoxy-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0060	uM
3-[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carbonyl]-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0060	uM
1,2-benzoxazol-3-yl-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0063	uM
methyl 2-[(3aS,6aR)-5-[2-(trifluoromethyl)phenyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-6-methylpyrimidine-4-carboxylate	1235542: Displacement of [3H]-retinol from RBP4 (unknown origin) by scintillation proximity assay	ic50	0.0063	uM
(6-methoxyimidazo[1,2-b]pyridazin-2-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0064	uM
1H-indazol-3-yl-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0064	uM
(6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl)-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone	1509090: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis	ic50	0.0067	uM
N-[2-(methylsulfonylcarbamoyl)phenyl]-4-[2-(trifluoromethyl)phenyl]piperidine-1-carboxamide	1163674: Antagonist activity at maltose binding protein-tagged RBP4 (unknown origin) expressed in Escherichia coli assessed as inhibition of retinol-induced protein/transthyretin interaction by HTRF assay	ic50	0.0068	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
Vitamin A	affects binding, decreases reaction, increases reaction, decreases expression, decreases secretion	5
Estradiol	affects expression, increases expression, increases secretion, affects cotreatment	4
Dexamethasone	increases expression, affects cotreatment	3
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects expression	1
terbufos	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases activity, decreases phosphorylation, increases expression, decreases reaction, increases abundance (+1 more)	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
bleomycetin	decreases expression	1
tetrachlorodian	increases expression	1
corosolic acid	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Acetaminophen	decreases expression	1
Allergens	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Fonofos	increases methylation	1

ChEMBL screening assays

32 unique, capped per target: 29 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1804183	Binding	Binding affinity to His-tagged recombinant human sRBP expressed in Escherichia coli BL21(DE3) assessed as apparent dissociation constant after 5 mins by fluorescence spectrophotometric analysis	Fenretinide derivatives act as disrupters of interactions of serum retinol binding protein (sRBP) with transthyretin and the sRBP receptor. — J Med Chem
CHEMBL1804187	Functional	Antagonist activity at His-tagged recombinant human sRBP expressed in Escherichia coli BL21(DE3) assessed as disruption of ROH-sRBP-TTR protein interaction after 2 hr by TR-FRET assay	Fenretinide derivatives act as disrupters of interactions of serum retinol binding protein (sRBP) with transthyretin and the sRBP receptor. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1YQ	Abcam A-549 RBP4 KO	Cancer cell line	Male
CVCL_D6BN	HyCyte Hep-G2 KO-hRBP4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT03748732	Not specified	UNKNOWN	Extensive Circumferential Partial Thickness Sclerectomy in Nanophthalmic Eyes
NCT04759560	Not specified	UNKNOWN	Biometric Characteristics of the Eye With Microcornea/Microphthalmia and Congenital Cataract Before And After Cataract Extraction
NCT05954403	Not specified	RECRUITING	National Cohort on Congenital Defects of the Eye
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD
NCT00368004	Not specified	TERMINATED	Family Studies of Uveal Coloboma
NCT04833361	Not specified	COMPLETED	Potential Environmental Causes of Uveal Coloboma
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
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