RBP1

Summary

RBP1 (retinol binding protein 1, HGNC:9919) is a protein-coding gene on chromosome 3q23, encoding Retinol-binding protein 1 (P09455). Cytoplasmic retinol-binding protein.

This gene encodes the carrier protein involved in the transport of retinol (vitamin A alcohol) from the liver storage site to peripheral tissue. Vitamin A is a fat-soluble vitamin necessary for growth, reproduction, differentiation of epithelial tissues, and vision. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5947 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• Druggable target: yes
• MANE Select transcript: NM_002899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9919
Approved symbol	RBP1
Name	retinol binding protein 1
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	CRABP-I, CRBP1, CRBP, RBPC, CRBPI, CRBP-I, hCRBP1
Ensembl gene	ENSG00000114115
Ensembl biotype	protein_coding
OMIM	180260
Entrez	5947

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000474490, ENST00000483943, ENST00000487424, ENST00000492918, ENST00000617459, ENST00000619087, ENST00000672186, ENST00000890713, ENST00000890714, ENST00000939445

RefSeq mRNA: 4 — MANE Select: NM_002899 NM_001130992, NM_001130993, NM_001365940, NM_002899

CCDS: CCDS3110, CCDS46925, CCDS46926, CCDS93396

Canonical transcript exons

ENST00000672186 — 4 exons

Exon	Start	End
ENSE00000778986	139518421	139518522
ENSE00002127375	139538781	139538959
ENSE00003723860	139517438	139517680
ENSE00003895073	139539460	139539742

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8866 / max 1261.0928, expressed in 1192 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44797	12.3390	968
44798	9.0066	1089
44796	5.1336	711
44794	0.8215	301
44795	0.5585	247
44799	0.0273	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.81	gold quality
retina	UBERON:0000966	99.78	gold quality
right uterine tube	UBERON:0001302	99.60	gold quality
body of pancreas	UBERON:0001150	99.46	gold quality
left ovary	UBERON:0002119	99.41	gold quality
right adrenal gland	UBERON:0001233	99.39	gold quality
right adrenal gland cortex	UBERON:0035827	99.37	gold quality
adenohypophysis	UBERON:0002196	99.34	gold quality
left adrenal gland	UBERON:0001234	99.32	gold quality
left adrenal gland cortex	UBERON:0035825	99.32	gold quality
adrenal cortex	UBERON:0001235	99.16	gold quality
adrenal gland	UBERON:0002369	99.06	gold quality
gall bladder	UBERON:0002110	99.04	gold quality
decidua	UBERON:0002450	99.04	gold quality
adrenal tissue	UBERON:0018303	98.96	gold quality
left uterine tube	UBERON:0001303	98.94	gold quality
pituitary gland	UBERON:0000007	98.92	gold quality
right ovary	UBERON:0002118	98.91	gold quality
ovary	UBERON:0000992	98.79	gold quality
islet of Langerhans	UBERON:0000006	98.38	gold quality
pancreas	UBERON:0001264	98.18	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.33	gold quality
body of uterus	UBERON:0009853	97.13	gold quality
embryo	UBERON:0000922	96.60	gold quality
right lobe of liver	UBERON:0001114	96.44	gold quality
ganglionic eminence	UBERON:0004023	96.25	gold quality
cranial nerve II	UBERON:0000941	95.99	gold quality
spinal cord	UBERON:0002240	95.85	gold quality
stromal cell of endometrium	CL:0002255	95.78	gold quality
choroid plexus epithelium	UBERON:0003911	95.77	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	5872.72
E-MTAB-6701	yes	5633.08
E-HCAD-24	yes	4979.12
E-GEOD-135922	yes	4264.31
E-MTAB-6678	yes	2867.28
E-GEOD-124263	yes	2330.12
E-MTAB-7407	yes	2263.67
E-MTAB-10287	yes	1709.97
E-HCAD-5	yes	1542.47
E-MTAB-10485	yes	1541.39
E-MTAB-8894	yes	1272.52
E-HCAD-10	yes	1082.13
E-MTAB-6911	yes	1076.99
E-MTAB-6308	yes	1009.08
E-ANND-5	yes	641.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting RBP1, 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-3658	99.96	73.87	4379
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-4298	97.26	66.59	765
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-3622B-5P	94.62	64.58	835

Literature-anchored findings (GeneRIF, showing 40)

• a high CRBP-1 expression is associated with smooth muscle malignancy and suggest that CRBP-1 expression represents a new useful marker for the classification of unusual variants of smooth muscle tumors (PMID:12111198)
• CRBP1 has a role in vitamin A metabolism and its absence may play a role in ovarian cancer oncogenesis (PMID:12631600)
• may serve as a surrogate marker for graft dysfunction early after kidney transplantation (PMID:12826154)
• in liver cancer modulation of CRBP-1 expression in HCCs contributes to tumor growth and progression via retinoid-mediated signaling and disruption of cellular vitamin A homeostasis. (PMID:12883492)
• Colocalization of plasma retinol-binding protein with RPE65 and affinity binding suggest a direct interaction of RPE65 with plasma retinol-binding protein in cultured human keratinocytes that might be involved in retinoid uptake of keratinocytes. (PMID:15009723)
• in fibrotic or cirrhotic liver, the different patterns of expression for CRBP-1 and alpha-SMA allow the distinction of different subsets of fibroblastic cells involved in fibrogenesis and septa formation (PMID:15094224)
• CRBP-I downregulation in cancer promotes tumor progression through inhibition of retinoic acid receptor activity and derepression of PI3K/Akt signaling via a novel mechanism. (PMID:15608670)
• The widely expressed CRBP1, which binds all-trans-retinol with much higher affinity than all-trans-retinaldehyde, restricts the oxidation of all-trans-retinol by retinol dehydrogenase 12 but has little effect on the reduction of all-trans-retinaldehyde. (PMID:15865448)
• CRBP-1+ cells increased in squamous intraepithelial lesions and slightly decreased in invasive squamous cell carcinomas. (PMID:17593084)
• Retinoic acid and retinol regulate expression of cellular retinol binding protein 1 and cellular RA binding protein 2 in fibroid and myometrial cells. (PMID:18343808)
• CRBP-1 clearly stains liver lobular HSCs without reacting with smooth muscle cells (SMCs) and shows variable cholangiocyte p (PMID:19052772)
• Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma. (PMID:19288010)
• protein-ligand interaction differences between CRBP-I and CRBP-II (PMID:19965581)
• CRBP1 gene could have a tumor suppressive function in bladder cancer. (PMID:21042705)
• It is likely that mutations in RGR, RBP3, and possibly RBP1 occur rarely in inherited retinal dystrophies. (PMID:21067480)
• CDK-mediated phosphorylation of both RBP1 and pRb induces their dissociation to mediate release of the mSin3.HDAC transcriptional repressor complex from pRb to alleviate transcriptional repression of E2F. (PMID:21148318)
• STRA6 not only is a vitamin A transporter but also is a cell-surface signaling receptor activated by the RBP-retinol complex. (PMID:21368206)
• Data show that CRBPI and CRBPII bind 9-cis-retinol and 9-cis-retinal with high affinities, albeit with affinities somewhat lower than for all-trans-retinol and all-trans-retinal. (PMID:21382444)
• Increased expression and unmethylated promoter of the CRBP1 gene could be considered as markers for larynx cancer. (PMID:22049223)
• CRBP-1 plays a role in ventricular remodeling after myocardial infarction allegedly through its RA binding activity. (PMID:22449228)
• RBP1 promoter hypermethylation is found in nearly all IDH1 and IDH2 mutant gliomas Because RBP1 is involved in retinoic acid synthesis, results suggest that dysregltion of RA metabolism may contribute to glioma formation along the IDH1/IDH2-mutant pathway (PMID:22945948)
• High urine retinol binding protein is associated with interstitial fibrosis and tubular atrophy plus inflammation. (PMID:23414180)
• Functional hepatic stellate cells coexpressing both LRAT and CRBP-1, that continue to maintain the ability to store vitamin A, contribute in part to the development of portal and parenchymal fibrogenesis in patients with viral hepatitis. (PMID:23890161)
• Suggest CRBP1 gene as a tumor suppressor gene for cervical cancer. (PMID:24040446)
• Factors involved in the retinoid pathway, in particular upregulation of CRBP, CRABP1 and CRABP2, also showed differential expression in tumors with different histological subtypes (PMID:24269351)
• CRBP-1 loss in G2/G3 ovarian carcinomas and increased apoptotic susceptibility to retinoids. (PMID:24982334)
• RBP1 expression was reduced in tissue and endometrial stromal cells derived from endometritis lesions versus eutopic endometruim in humans and mice. (PMID:25143356)
• Hypermethylation of CRBP1 gene is associated with Epstein-Barr virus-associated gastric carcinomas. (PMID:25720522)
• Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients screening for a more personalized and efficacy retinoid therapy (PMID:25879031)
• This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. (PMID:26900151)
• Low CRBP1 expression is associated with low radiation sensitivity in rectal cancer. (PMID:28291773)
• molecular dynamics simulations for the uptake of retinol by CRBP 1 and 2 (PMID:29567208)
• Up-regulated expression of CRBP-1 is associated with poor prognosis in tongue squamous cell carcinoma (PMID:29720147)
• The levels of urinary retinol-binding protein (uRBP) were significantly higher in patients infected with cytomegalovirus (CMV) at the time of diagnosis. (PMID:30171051)
• CRBP1 expression was significantly increased in lesional alopecia areata skin in comparison with normal skin of controls. Significant positive correlation was found between expression of CRBP-1 and percentage of hair loss in the scalp. (PMID:30556317)
• The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma. (PMID:32587255)
• Cellular retinol binding protein 1 transfection reduces proliferation and AKT-related gene expression in H460 non-small lung cancer cells. (PMID:32909215)
• Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/beta-catenin pathway in hepatocellular carcinoma. (PMID:34775955)
• Retinol binding protein 1-dependent activation of NF- kappaB signaling enhances the malignancy of non-glioblastomatous diffuse gliomas. (PMID:34866280)
• MicroRNA-20a-5p inhibits the autophagy and cisplatin resistance in ovarian cancer via regulating DNMT3B-mediated DNA methylation of RBP1. (PMID:34990753)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbp1.1	ENSDARG00000018077
danio_rerio	rbp1.2	ENSDARG00000038742
mus_musculus	Rbp1	ENSMUSG00000046402
drosophila_melanogaster	fabp	FBGN0037913
caenorhabditis_elegans		WBGENE00002259
caenorhabditis_elegans		WBGENE00002260

Paralogs (15): RBP2 (ENSG00000114113), FABP3 (ENSG00000121769), RBP5 (ENSG00000139194), CRABP2 (ENSG00000143320), FABP2 (ENSG00000145384), PMP2 (ENSG00000147588), RBP7 (ENSG00000162444), FABP1 (ENSG00000163586), FABP7 (ENSG00000164434), FABP5 (ENSG00000164687), CRABP1 (ENSG00000166426), FABP6 (ENSG00000170231), FABP4 (ENSG00000170323), FABP12 (ENSG00000197416), FABP9 (ENSG00000205186)

Protein

Protein identifiers

Retinol-binding protein 1 — P09455 (reviewed: P09455)

Alternative names: Cellular retinol-binding protein, Cellular retinol-binding protein I

All UniProt accessions (4): P09455, A0A0A0MQT0, A0A0A0MTB9, H0YAK8

UniProt curated annotations — full annotation on UniProt →

Function. Cytoplasmic retinol-binding protein. Accepts retinol from the transport protein STRA6, and thereby contributes to retinol uptake, storage and retinoid homeostasis.

Subunit / interactions. Interacts (only as retinol-free apoprotein) with STRA6.

Subcellular location. Cytoplasm. Lipid droplet.

Tissue specificity. Detected in nearly all the tissues with higher expression in adult ovary, pancreas, pituitary gland and adrenal gland, and fetal liver.

Domain organisation. Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.

Similarity. Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.

Isoforms (3)

UniProt ID	Names	Canonical?
P09455-1	1	yes
P09455-2	2
P09455-3	3

RefSeq proteins (4): NP_001124464, NP_001124465, NP_001352869, NP_002890* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000463	Fatty_acid-bd	Domain
IPR000566	Lipocln_cytosolic_FA-bd_dom	Domain
IPR012674	Calycin	Homologous_superfamily
IPR031259	ILBP	Family
IPR031264	CRBP1	Family

Pfam: PF00061

UniProt features (31 total): strand 10, mutagenesis site 7, binding site 3, splice variant 3, helix 2, modified residue 2, chain 1, region of interest 1, turn 1, sequence conflict 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
5HBS	X-RAY DIFFRACTION	0.89
8GD2	X-RAY DIFFRACTION	1.13
5LJG	X-RAY DIFFRACTION	1.15
6E5L	X-RAY DIFFRACTION	1.17
5H8T	X-RAY DIFFRACTION	1.21
5LJB	X-RAY DIFFRACTION	1.26
8GEY	X-RAY DIFFRACTION	1.3
5HA1	X-RAY DIFFRACTION	1.35
5H9A	X-RAY DIFFRACTION	1.38
5LJE	X-RAY DIFFRACTION	1.4
5LJC	X-RAY DIFFRACTION	1.43
8GEU	X-RAY DIFFRACTION	1.47
5LJH	X-RAY DIFFRACTION	1.52
6E5T	X-RAY DIFFRACTION	1.55
6E6M	X-RAY DIFFRACTION	1.55
8GEM	X-RAY DIFFRACTION	1.55
5LJD	X-RAY DIFFRACTION	1.61
5LJK	X-RAY DIFFRACTION	1.7
8GDM	X-RAY DIFFRACTION	1.8
8GEV	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09455-F1	96.81	0.96

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): 41; 63; 109

Post-translational modifications (2): 9, 9

Mutagenesis-validated functional residues (7):

Position	Phenotype
31	no effect on retinol binding. abolishes interaction with sta6 and the ability to enhance sta6-mediated vitamin a uptake.
32	no effect on retinol binding. abolishes interaction with sta6 and the ability to enhance sta6-mediated vitamin a uptake.
41	strongly decreased affinity for retinol. further decrease in affinity for retinol; when associated with l-109.
59	decreases cellular retinol uptake and impairs retinol storage.
109	strongly decreased affinity for retinol. further decrease in for retinol; when associated with l-41.
22	no effect on retinol binding. abolishes interaction with sta6 and the ability to enhance sta6-mediated vitamin a uptake.
30	decreases cellular retinol uptake and impairs retinol storage.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9918442	Defective visual phototransduction due to LRAT loss of function

MSigDB gene sets: 249 (showing top): MODULE_52, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, JI_RESPONSE_TO_FSH_UP, GRUETZMANN_PANCREATIC_CANCER_DN, KAAB_FAILED_HEART_ATRIUM_DN, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, MODULE_404, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, ZHAN_MULTIPLE_MYELOMA_CD1_UP, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_LIPID_HOMEOSTASIS, MODULE_66

GO Biological Process (10): retinoic acid biosynthetic process (GO:0002138), vitamin A metabolic process (GO:0006776), fatty acid transport (GO:0015908), lipid homeostasis (GO:0055088), retinoid metabolic process (GO:0001523), lipid storage (GO:0019915), regulation of granulocyte differentiation (GO:0030852), response to vitamin A (GO:0033189), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573)

GO Molecular Function (7): retinoid binding (GO:0005501), fatty acid binding (GO:0005504), retinal binding (GO:0016918), all-trans-retinol binding (GO:1904768), protein binding (GO:0005515), lipid binding (GO:0008289), retinol binding (GO:0019841)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), lipid droplet (GO:0005811), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Visual phototransduction	2
Metabolism of fat-soluble vitamins	1
Retinoid cycle disease events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid metabolic process	3
cellular anatomical structure	3
hormone metabolic process	2
retinoid binding	2
vitamin binding	2
binding	2
diterpenoid biosynthetic process	1
retinoic acid metabolic process	1
monocarboxylic acid biosynthetic process	1
lipid transport	1
monocarboxylic acid transport	1
chemical homeostasis	1
diterpenoid metabolic process	1
nutrient storage	1
regulation of myeloid leukocyte differentiation	1
granulocyte differentiation	1
response to vitamin	1
response to lipid	1
primary alcohol metabolic process	1
olefinic compound metabolic process	1
monocarboxylic acid metabolic process	1
isoprenoid binding	1
lipid binding	1
monocarboxylic acid binding	1
retinol binding	1
alcohol binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBP1	STRA6	Q9BX79	959
RBP1	RDH11	Q8TC12	909
RBP1	RLBP1	P12271	862
RBP1	RBP4	P02753	820
RBP1	LRAT	O95237	814
RBP1	RBP3	P10745	802
RBP1	ALDH1A1	P00352	746
RBP1	RARS1	P54136	719
RBP1	CYP26A1	O43174	714
RBP1	RDH12	Q96NR8	702
RBP1	RARB	P10826	701
RBP1	RDH10	Q8IZV5	692
RBP1	RARA	P10276	678
RBP1	ADH1A	P07327	655
RBP1	RARG	P13631	655

IntAct

36 interactions, top by confidence:

A	B	Type	Score
ARPC1A	ARPC2	psi-mi:“MI:0914”(association)	0.900
RBP1	DHPS	psi-mi:“MI:0915”(physical association)	0.560
RBP1	UBE2J2	psi-mi:“MI:0915”(physical association)	0.560
RBP1	TTC19	psi-mi:“MI:0915”(physical association)	0.560
RBP1	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
SOX2	PDLIM1	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
SLC4A5	RBP1	psi-mi:“MI:0915”(physical association)	0.400
RBP1	EBNA2	psi-mi:“MI:0915”(physical association)	0.370
RBP1	IKBKG	psi-mi:“MI:0915”(physical association)	0.370
SHLD3		psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
FAM24B	SHTN1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
SFR1	CTSV	psi-mi:“MI:0914”(association)	0.350
OR52N4	RBP1	psi-mi:“MI:0914”(association)	0.350
EEF2K	RBP1	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
RAE1	NHERF1	psi-mi:“MI:0914”(association)	0.350
DHPS	RBP1	psi-mi:“MI:0915”(physical association)	0.000
RBP1	UBE2J2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): RBP1 (Affinity Capture-Western), RBP1 (Affinity Capture-Western), CUL4B (Affinity Capture-Western), DDB1 (Affinity Capture-Western), RBP1 (Affinity Capture-MS), RBP1 (Affinity Capture-MS), RBP1 (Affinity Capture-MS), RBP1 (Two-hybrid), RBP1 (Two-hybrid), UBE2J2 (Two-hybrid), TNFRSF10D (Two-hybrid), RBP1 (Affinity Capture-MS), LRP2 (Reconstituted Complex), RBP1 (Affinity Capture-MS), RBP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K0MJN3, A6NFH5, B7SUM8, C4N147, O01812, O01814, O02323, O02324, O02772, O08716, O15540, P02694, P02696, P05413, P06768, P09455, P0C6G6, P10790, P15090, P24526, P29498, P41496, P41509, P48035, P50120, P50121, P51880, P55051, P55054, P70623, P80049, P82708, P82980, Q00915, Q02970, Q05423, Q05816, Q08652, Q09139, Q0Z7S8

Diamond homologs: A0A0K0MJ13, A0A0K0MJN3, A6NFH5, A6YLM6, A8MUU1, B7SUM8, C4N147, O01812, O01814, O02323, O02324, O02772, O08716, O13008, O15540, O42386, O45035, O76821, O97788, P02689, P02690, P02691, P02694, P02696, P04117, P05413, P06768, P07148, P07483, P09455, P0C6G6, P10790, P11404, P12710, P15090, P22935, P24526, P29373, P29498, P29762

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RBP1	“up-regulates quantity”	retinol	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1315 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:139538791:C:G	R81P	0.998
3:139518422:A:G	L118P	0.997
3:139518456:A:G	W107R	0.997
3:139518456:A:T	W107R	0.997
3:139538820:A:C	F71L	0.997
3:139538820:A:T	F71L	0.997
3:139538822:A:G	F71L	0.997
3:139538865:G:C	S56R	0.997
3:139538865:G:T	S56R	0.997
3:139538867:T:G	S56R	0.997
3:139538932:G:T	A34D	0.996
3:139517642:G:C	F131L	0.995
3:139517642:G:T	F131L	0.995
3:139517644:A:G	F131L	0.995
3:139518428:A:G	L116P	0.995
3:139518454:C:A	W107C	0.995
3:139518454:C:G	W107C	0.995
3:139538838:G:C	F65L	0.995
3:139538838:G:T	F65L	0.995
3:139538840:A:G	F65L	0.995
3:139538910:T:A	K41N	0.995
3:139538910:T:G	K41N	0.995
3:139539514:C:A	G7W	0.995
3:139518494:A:G	L94P	0.994
3:139538875:C:G	R53P	0.994
3:139538941:C:G	R31P	0.994
3:139539471:A:G	L21P	0.994
3:139517654:G:C	C127W	0.993
3:139518462:G:T	R105S	0.993
3:139518481:C:A	Q98H	0.993

dbSNP variants (sampled 300 via entrez): RS1000057420 (3:139534419 G>C), RS1000099263 (3:139520603 A>G), RS1000256353 (3:139520789 A>G), RS1000402166 (3:139520902 T>A), RS1000430970 (3:139528189 C>A,T), RS1000830108 (3:139526466 T>C), RS1000884105 (3:139526293 G>A), RS1000962308 (3:139525982 A>G), RS1001083410 (3:139539856 G>A,C), RS1001104609 (3:139533837 TC>T), RS1001234643 (3:139534041 T>A,G), RS1001406773 (3:139540581 C>T), RS1001468071 (3:139533109 A>G), RS1001508955 (3:139519121 A>C,G,T), RS1001701091 (3:139532208 G>T)

Disease associations

OMIM: gene MIM:180260 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2076 (SINGLE PROTEIN)

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

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.17	Ki	67	nM	CHEMBL5559991
5.15	Ki	7100	nM	CHEMBL5559914
5.15	Ki	7100	nM	CHEMBL5556282
5.15	Ki	7100	nM	CHEMBL5563667
5.15	Ki	7100	nM	CHEMBL5568461
5.15	Ki	7100	nM	CHEMBL5566589
5.15	Ki	7100	nM	CHEMBL1598041

PubChem BioAssay actives

7 with measured affinity, of 7 total; 7 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-pentyl-4-[(1R)-2-prop-1-en-2-ylcyclohexyl]benzene-1,3-diol	2082672: Binding affinity to human recombinant CRBP1 assessed as inhibition constant	ki	0.0670	uM
N-methyl-N-[[3-[1-(4-methylphenyl)cyclopentyl]-1,2,4-oxadiazol-5-yl]methyl]-1-(1-methylpyrazol-4-yl)methanamine	2082673: Binding affinity to CRBP1 (unknown origin) assessed as inhibition constant	ki	7.1000	uM
N-methyl-N-[[3-[1-(4-methylphenyl)cyclopentyl]-1,2,4-oxadiazol-5-yl]methyl]-1-thiophen-2-ylmethanamine	2082673: Binding affinity to CRBP1 (unknown origin) assessed as inhibition constant	ki	7.1000	uM
3-benzhydryl-5-[[4-(methoxymethyl)piperidin-1-yl]methyl]-1,2,4-oxadiazole	2082673: Binding affinity to CRBP1 (unknown origin) assessed as inhibition constant	ki	7.1000	uM
N-ethyl-N-[[3-[1-(4-methylphenyl)cyclopentyl]-1,2,4-oxadiazol-5-yl]methyl]-2-pyrazol-1-ylethanamine	2082673: Binding affinity to CRBP1 (unknown origin) assessed as inhibition constant	ki	7.1000	uM
N-[(3-benzhydryl-1,2,4-oxadiazol-5-yl)methyl]-N-methyl-1-thiophen-2-ylethanamine	2082673: Binding affinity to CRBP1 (unknown origin) assessed as inhibition constant	ki	7.1000	uM
4-(hydroxymethyl)-1-[(4-methoxy-5,6,7,8-tetrahydronaphthalen-1-yl)sulfonyl]piperidin-4-ol	2082673: Binding affinity to CRBP1 (unknown origin) assessed as inhibition constant	ki	7.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Tretinoin	increases expression, increases reaction, affects binding	7
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	5
Estradiol	increases expression, affects cotreatment, decreases expression	5
Cisplatin	affects cotreatment, increases expression, affects response to substance, increases response to substance	4
trichostatin A	affects cotreatment, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
methylmercuric chloride	decreases expression, increases expression	2
Decitabine	increases expression, increases reaction, decreases metabolic processing	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Ethinyl Estradiol	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Vitamin A	increases uptake, increases expression	2
Genistein	decreases expression	2
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
potassium perchlorate	decreases expression	1
propargylglycine	decreases reaction, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
diallyl trisulfide	affects cotreatment, decreases reaction, increases expression	1
pentanal	increases expression	1
3,5-di-tert-butylchalcone 4’-carboxylic acid	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5522713	Binding	Binding affinity to human recombinant CRBP1 assessed as inhibition constant	Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins. — J Med Chem

Clinical trials (associated diseases)

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