CRABP2

Summary

CRABP2 (cellular retinoic acid binding protein 2, HGNC:2339) is a protein-coding gene on chromosome 1q23.1, encoding Cellular retinoic acid-binding protein 2 (P29373). Transports retinoic acid to the nucleus.

This gene encodes a member of the retinoic acid (RA, a form of vitamin A) binding protein family and lipocalin/cytosolic fatty-acid binding protein family. The protein is a cytosol-to-nuclear shuttling protein, which facilitates RA binding to its cognate receptor complex and transfer to the nucleus. It is involved in the retinoid signaling pathway, and is associated with increased circulating low-density lipoprotein cholesterol. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 1382 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 37 total
• Druggable target: yes
• MANE Select transcript: NM_001878

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2339
Approved symbol	CRABP2
Name	cellular retinoic acid binding protein 2
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	CRABP-II
Ensembl gene	ENSG00000143320
Ensembl biotype	protein_coding
OMIM	180231
Entrez	1382

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000368220, ENST00000368221, ENST00000368222, ENST00000621784, ENST00000858003, ENST00000858004, ENST00000926904, ENST00000926905, ENST00000926906, ENST00000926907, ENST00000926908, ENST00000926909, ENST00000926910, ENST00000926911

RefSeq mRNA: 2 — MANE Select: NM_001878 NM_001199723, NM_001878

CCDS: CCDS1152

Canonical transcript exons

ENST00000368222 — 4 exons

Exon	Start	End
ENSE00000959257	156700874	156701052
ENSE00000959258	156700542	156700658
ENSE00001446614	156699606	156700076
ENSE00001446616	156705377	156705583

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 85.4448 / max 1883.5826, expressed in 1327 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15183	83.0819	1316
15185	2.2244	677
15184	0.1384	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.57	gold quality
esophagus mucosa	UBERON:0002469	99.01	gold quality
gingiva	UBERON:0001828	98.69	gold quality
gingival epithelium	UBERON:0001949	98.46	gold quality
mammalian vulva	UBERON:0000997	98.44	gold quality
oral cavity	UBERON:0000167	97.55	gold quality
esophagus squamous epithelium	UBERON:0006920	97.43	gold quality
skin of abdomen	UBERON:0001416	97.39	gold quality
epithelium of esophagus	UBERON:0001976	97.24	gold quality
pharyngeal mucosa	UBERON:0000355	97.01	gold quality
skin of leg	UBERON:0001511	96.75	gold quality
upper arm skin	UBERON:0004263	96.71	gold quality
zone of skin	UBERON:0000014	96.36	gold quality
vagina	UBERON:0000996	95.51	gold quality
squamous epithelium	UBERON:0006914	95.38	gold quality
mammary duct	UBERON:0001765	94.61	gold quality
cervix epithelium	UBERON:0004801	94.55	gold quality
penis	UBERON:0000989	94.38	gold quality
upper leg skin	UBERON:0004262	94.38	gold quality
right uterine tube	UBERON:0001302	94.00	gold quality
stromal cell of endometrium	CL:0002255	93.91	gold quality
endometrium epithelium	UBERON:0004811	93.42	gold quality
epithelium of mammary gland	UBERON:0003244	92.43	gold quality
smooth muscle tissue	UBERON:0001135	91.99	gold quality
uterine cervix	UBERON:0000002	91.79	gold quality
tongue squamous epithelium	UBERON:0006919	90.74	silver quality
adenohypophysis	UBERON:0002196	90.12	gold quality
nipple	UBERON:0002030	89.82	gold quality
esophagus	UBERON:0001043	89.74	gold quality
fallopian tube	UBERON:0003889	89.65	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	2301.67
E-HCAD-1	yes	1749.02
E-MTAB-6108	yes	1694.63
E-MTAB-10018	yes	1366.12
E-MTAB-8142	yes	1300.04
E-GEOD-124472	yes	1151.37
E-HCAD-10	yes	977.80
E-HCAD-56	yes	939.66
E-HCAD-5	yes	875.55
E-MTAB-7407	yes	831.72
E-MTAB-10485	yes	807.66
E-GEOD-114530	yes	776.59
E-CURD-79	yes	732.95
E-MTAB-8271	yes	646.72
E-CURD-11	yes	586.47

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
RARA	Activation

Upstream regulators (CollecTRI, top): CEBPA, CREM, EGR1, ESR1, MED1, MYCN, NCOA1, PBRM1, PGR, RARA, RARB, RARG, RXRA, TFAP2A, TFAP2C

miRNA regulators (miRDB)

28 targeting CRABP2, 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-3163	100.00	77.23	8605
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 40)

• Direct channeling of retinoic acid between cellular retinoic acid-binding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid-induced growth arrest. (PMID:11909957)
• Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of this protein (PMID:12482873)
• In this study, we excluded mutations within the complete coding region and the promoter of LMNA and the CRABP II gene in HIV-1 infected patients with lipodystrophy (PMID:12844477)
• CRABP-II has a role in wound re-epithelialisation by dermal fibroblasts (PMID:14766225)
• Phosphorylation/dephosphorylation of retinoic x receptor alpha via protein kinase C may be involved in the regulation of CRABP-II gene expression. (PMID:15225641)
• Data suggest that the ligand-controlled nuclear localization signal of CRABP-II may represent a general mechanism for posttranslational regulation of the subcellular distribution of a protein. (PMID:15866176)
• Transient transfection of either all-trans-retinoic acid (ATRA) receptor alpha or estrogen receptor alpha expression vectors increased CRABPII expression in MDA-MB-231 cells (PMID:15870697)
• CRABP-II overexpression in CAKI-2 RCC cells did not significantly influence RA associated antiproliferative actions. (PMID:16215318)
• MycN binds to the promoter of CRABP-II and induces CRABP-II transcription directly in neuroblastoma. (PMID:16912187)
• Results describe the structure of apo-wild type (WT) CRABPII at 1.35 A and show that apo- and holo-CRABPII share very similar structures. (PMID:16979656)
• AP2 factors regulate CRABPII expression in human mammary epithelial cells and breast cancer cells (PMID:17187826)
• results show that the CRABP2 gene is associated with increased plasma LDL-C concentrations. Carriers of the C allele had significantly higher LDL-C in healthy males, HIV-infected patients, and patients with familial hypercholesterolemia (PMID:17484622)
• 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)
• MycN and DNA methylation are responsible for CRABP-II expression in pediatric tumors and demethylation of CRABP-II may be an early event in tumor development. (PMID:18955045)
• Derangement/lack of a critical factor necessary for RARalpha function induces epigenetic repression of a RA-regulated gene network downstream of RARalpha, with major pleiotropic biological outcomes. (PMID:19173001)
• Data sghow a higher frequency of CRABP2 and MX1 hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. (PMID:20019841)
• Individual variation in ALDH1A2/CRABP2 genes may account for subtle variations in retinoic acid-dependent human embryogenesis. (PMID:20308937)
• Data show that NIPER-4 induces cIAP1-mediated ubiquitylation of CRABP-II, resulting in the proteasomal degradation. (PMID:21414315)
• Trophoblast spheroids cocultured with endometrial cells overexpressing CRABP2 are defective in expansion and exhibit apoptosis, suggesting that CRABP2 is involved in abnormal endometrium-trophoblast interaction, leading to implantation failure. (PMID:21605859)
• Nuclear translocation of cellular retinoic acid-binding protein II is regulated by retinoic acid-controlled SUMOylation (PMID:21998312)
• Low CRABP2 is associated with pancreatic ductal adenocarcinoma. (PMID:22010213)
• Aberrant methylation in CRABP-II reduces the expression of CRABP-II that in turn confers retinoic acid resistance in medulloblastoma cells. (PMID:22153617)
• Hypermethylation in the CpG island of the CRABP2 gene is associated with astrocytic gliomas. (PMID:22275178)
• E-FABP showed high exp ression in NSCLC, and the increased E-FABP expression may involved in the occurrence and development of NSCLC (PMID:23327868)
• all three proteins (RDH10, RALDH2, and CRABP2) appeared to be required for ATRA production induced by activation of PPARgamma (PMID:23833249)
• Reengineering of cellular retinoic acid binding protein II (CRABPII) to be capable of binding retinal as a protonated Schiff base is described (PMID:24059243)
• 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)
• CRABP2 controls mRNA stabilization by HuR. (PMID:24687854)
• overexpression of CRABP-II is a late event of pancreatic carcinogenesis, and it could be used as a diagnostic marker (PMID:24709110)
• CBX3 and CRABP2 expression was markedly increased in lung cancer tissues (PMID:24751108)
• we demonstrated significant changes in CRABP1 and CRABP2 expression in non-small cell lung cancer samples (PMID:25034531)
• The anticarcinogenic activities of CRABP2 are mediated by both HuR and RAR. (PMID:25320093)
• in esophageal squamous carcinogenesis by significantly inhibiting cell growth, inducing cell apoptosis and blocking cell metastasis both in vitro and in vivo (PMID:26839961)
• reducing CRABP2 levels may enhance the therapeutic index of Retinoic acid in glioblastoma multiforme patients (PMID:26893190)
• Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs(CRABP-I and CRABP-II ) inhibited the formation of 4-OH-RA by CYP26B1. (PMID:27416800)
• A high expression ratio between FABP5 and CRABPII may be related to CP tumor recurrence and ATRA could be a potential therapeutic agent for CP chemotherapy. (PMID:27418530)
• These data suggest a retinoic acid-independent, non-tumor suppressor role of CRABP2 for the survival of Malignant peripheral nerve sheath tumor (MPNST) cells in vitro. Targeting CRABP2 overexpression may represent a unique approach for the treatment of human MPNST. (PMID:28502478)
• Semiquantitative and quantitative analyses of the markers RARA and CRABP2 indicate their potential as biomarkers for tumor progression and their participation in nephroblastoma tumorigenesis (PMID:29378601)
• ATRA increased the resistance to apoptosis despite the high CRABP2/FABP5 ratio of RA fibroblast-like synoviocytes (FLS); and CRABP2 suppression sensitized RA FLS to Fas-induced apoptosis. (PMID:29880835)
• Higher plasma CRABP2 levels were also correlated with lower survival rates in non-small cell lung cancer patients (PMID:29930489)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	crabp2b	ENSDARG00000030449
danio_rerio	crabp2a	ENSDARG00000073978
mus_musculus	Crabp2	ENSMUSG00000004885
rattus_norvegicus	Crabp2	ENSRNOG00000022101
drosophila_melanogaster	fabp	FBGN0037913
caenorhabditis_elegans		WBGENE00002259
caenorhabditis_elegans		WBGENE00002260

Paralogs (15): RBP2 (ENSG00000114113), RBP1 (ENSG00000114115), FABP3 (ENSG00000121769), RBP5 (ENSG00000139194), 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

Cellular retinoic acid-binding protein 2 — P29373 (reviewed: P29373)

Alternative names: Cellular retinoic acid-binding protein II

All UniProt accessions (2): P29373, Q5SYZ4

UniProt curated annotations — full annotation on UniProt →

Function. Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors.

Subunit / interactions. Interacts with RXR and RARA. Interacts with importin alpha.

Subcellular location. Cytoplasm. Endoplasmic reticulum. Nucleus.

Post-translational modifications. Sumoylated in response to retinoic acid binding, sumoylation is critical for dissociation from ER and subsequent nuclear translocation.

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

Induction. By retinoic acid.

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

RefSeq proteins (2): NP_001186652, NP_001869* (*=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

Pfam: PF00061

UniProt features (26 total): strand 15, helix 3, mutagenesis site 3, chain 1, short sequence motif 1, turn 1, binding site 1, cross-link 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OXW	X-RAY DIFFRACTION	1.16
2G7B	X-RAY DIFFRACTION	1.18
3D95	X-RAY DIFFRACTION	1.2
3CR6	X-RAY DIFFRACTION	1.22
7OXX	X-RAY DIFFRACTION	1.33
2FS6	X-RAY DIFFRACTION	1.35
4QGX	X-RAY DIFFRACTION	1.47
2FR3	X-RAY DIFFRACTION	1.48
3D97	X-RAY DIFFRACTION	1.5
6HKR	X-RAY DIFFRACTION	1.5
2FRS	X-RAY DIFFRACTION	1.51
3FEK	X-RAY DIFFRACTION	1.51
3FA6	X-RAY DIFFRACTION	1.54
2FS7	X-RAY DIFFRACTION	1.55
3FEN	X-RAY DIFFRACTION	1.56
4YKO	X-RAY DIFFRACTION	1.57
4YKM	X-RAY DIFFRACTION	1.58
6MPK	X-RAY DIFFRACTION	1.58
3CWK	X-RAY DIFFRACTION	1.6
4YFQ	X-RAY DIFFRACTION	1.62
6NNY	X-RAY DIFFRACTION	1.67
3I17	X-RAY DIFFRACTION	1.68
2G79	X-RAY DIFFRACTION	1.69
2G78	X-RAY DIFFRACTION	1.7
3D96	X-RAY DIFFRACTION	1.71
7AA1	X-RAY DIFFRACTION	1.71
4QGV	X-RAY DIFFRACTION	1.73
5HZQ	X-RAY DIFFRACTION	1.75
6MOV	X-RAY DIFFRACTION	1.75
4QGW	X-RAY DIFFRACTION	1.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29373-F1	96.84	0.98

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): 133–135

Post-translational modifications (1): 102

Mutagenesis-validated functional residues (3):

Position	Phenotype
21	loss of ligand-induced nuclear import; when associated with a-30 and a-31.
30	loss of ligand-induced nuclear import; when associated with a-21 and a-31.
31	loss of ligand-induced nuclear import; when associated with a-21 and a-30.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5362517	Signaling by Retinoic Acid

MSigDB gene sets: 298 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, TSENG_IRS1_TARGETS_UP, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, LI_WILMS_TUMOR, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_FORELIMB_MORPHOGENESIS

GO Biological Process (7): regulation of DNA-templated transcription (GO:0006355), signal transduction (GO:0007165), epidermis development (GO:0008544), fatty acid transport (GO:0015908), embryonic forelimb morphogenesis (GO:0035115), retinoic acid metabolic process (GO:0042573), positive regulation of collateral sprouting (GO:0048672)

GO Molecular Function (8): retinoic acid binding (GO:0001972), retinoid binding (GO:0005501), fatty acid binding (GO:0005504), retinal binding (GO:0016918), retinol binding (GO:0019841), cyclin binding (GO:0030332), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid binding	3
cellular anatomical structure	3
monocarboxylic acid binding	2
vitamin binding	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
tissue development	1
lipid transport	1
monocarboxylic acid transport	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
retinoid metabolic process	1
monocarboxylic acid metabolic process	1
hormone metabolic process	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
collateral sprouting	1
regulation of collateral sprouting	1
positive regulation of axonogenesis	1
isoprenoid binding	1
lipid binding	1
alcohol binding	1
protein binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
extracellular vesicle	1

Protein interactions and networks

STRING

1286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRABP2	RARB	P10826	938
CRABP2	RARG	P13631	881
CRABP2	RARA	P10276	812
CRABP2	PLAAT4	Q9UL19	752
CRABP2	PLAAT3	P53816	747
CRABP2	RARS1	P54136	742
CRABP2	PBRM1	Q86U86	742
CRABP2	S100A13	Q99584	742
CRABP2	ELAVL1	Q15717	738
CRABP2	PPARD	Q03181	728
CRABP2	CYP26C1	Q6V0L0	722
CRABP2	PLAAT1	Q9HDD0	717
CRABP2	CYP26A1	O43174	709
CRABP2	RBP3	P10745	649
CRABP2	RXRA	P19793	648

IntAct

61 interactions, top by confidence:

A	B	Type	Score
	TOMM70	psi-mi:“MI:0914”(association)	0.980
KASH5	CRABP2	psi-mi:“MI:0915”(physical association)	0.720
CRABP2	KASH5	psi-mi:“MI:0915”(physical association)	0.720
ACTN2	CRABP2	psi-mi:“MI:0915”(physical association)	0.560
CRABP2	CCND3	psi-mi:“MI:0915”(physical association)	0.560
CRABP2	FLAD1	psi-mi:“MI:0915”(physical association)	0.560
UGT1A10	A2ML1	psi-mi:“MI:0914”(association)	0.530
GDF5	SERPINB7	psi-mi:“MI:0914”(association)	0.530
CGREF1	TNKS	psi-mi:“MI:0914”(association)	0.530
DHDH	ATRN	psi-mi:“MI:0914”(association)	0.530
VPS50	PHF20L1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
PDE4DIP	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
FCF1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
RAB5A	EIF3CL	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
FAM24B	SHTN1	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (113): CCDC155 (Two-hybrid), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Two-hybrid), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Proximity Label-MS), CRABP2 (Affinity Capture-MS), CRABP2 (Two-hybrid), FLAD1 (Two-hybrid)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, B9N1F9, B9SQI7, E0CSI1, I3SPW2, O15305, O42386, O80526, O88600, O97555, O97556, P21856, P22935, P29373, P29762, P31150, P34932, P40220, P50396, P50398, P50568, P51673, P60028, P62964, P62965, P62966, Q2QNG7, Q2QZ86, Q2TFN9, Q3C1F4, Q42785, Q5PXY7, Q5R2J5, Q5R5C9, Q5RDM4, Q5ZID6, Q60HD6, Q61316, Q6AY30

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

4 interactions.

A	Effect	B	Mechanism
PBRM1	“up-regulates quantity by expression”	CRABP2	“transcriptional regulation”
TFAP2C	“up-regulates quantity by expression”	CRABP2	“transcriptional regulation”
TFAP2A	“up-regulates quantity by expression”	CRABP2	“transcriptional regulation”
CRABP2	up-regulates	Metastasis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

303 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156700076:TC:T	acceptor_loss	1.0000
1:156700077:C:CA	acceptor_loss	1.0000
1:156700077:C:CC	acceptor_gain	1.0000
1:156700078:T:C	acceptor_loss	1.0000
1:156700535:GACTT:G	donor_loss	1.0000
1:156700536:ACTTA:A	donor_loss	1.0000
1:156700537:CTTA:C	donor_loss	1.0000
1:156700538:TTA:T	donor_loss	1.0000
1:156700539:TACCA:T	donor_loss	1.0000
1:156700540:A:AC	donor_gain	1.0000
1:156700540:AC:A	donor_gain	1.0000
1:156700541:C:CT	donor_gain	1.0000
1:156700541:C:G	donor_loss	1.0000
1:156700541:CC:C	donor_gain	1.0000
1:156700541:CCA:C	donor_gain	1.0000
1:156700541:CCAGG:C	donor_gain	1.0000
1:156700654:AGGCT:A	acceptor_gain	1.0000
1:156700655:GGCT:G	acceptor_gain	1.0000
1:156700657:CT:C	acceptor_gain	1.0000
1:156700659:C:CC	acceptor_gain	1.0000
1:156700659:CTGC:C	acceptor_loss	1.0000
1:156700660:T:G	acceptor_loss	1.0000
1:156700869:CTCA:C	donor_loss	1.0000
1:156700871:CA:C	donor_loss	1.0000
1:156700872:ACC:A	donor_loss	1.0000
1:156700873:CCTTA:C	donor_gain	1.0000
1:156701048:CACCC:C	acceptor_gain	1.0000
1:156701049:ACCC:A	acceptor_gain	1.0000
1:156701050:CCC:C	acceptor_gain	1.0000
1:156701050:CCCC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000427804 (1:156699430 G>A,C), RS1000820964 (1:156700317 G>A,C), RS1000902698 (1:156703889 G>A,C), RS1001161241 (1:156706229 A>T), RS1001268989 (1:156699825 A>G), RS1002166943 (1:156704783 C>T), RS1002223841 (1:156701948 G>A), RS1002814169 (1:156703705 G>C,T), RS1002834734 (1:156707537 G>A), RS1002886002 (1:156700855 A>G), RS1003974401 (1:156707637 G>A), RS1004181787 (1:156701996 G>C), RS1004487149 (1:156701571 C>T), RS1004611645 (1:156700229 C>G,T), RS1005179804 (1:156706811 G>A,T)

Disease associations

OMIM: gene MIM:180231 | 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 (3): CHEMBL2221342 (PROTEIN COMPLEX), CHEMBL2692 (SINGLE PROTEIN), CHEMBL6193808 (PROTEIN-PROTEIN INTERACTION)

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

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

pChembl	Type	Value	Unit	Molecule
6.80	Kd	160	nM	CHEMBL451835

PubChem BioAssay actives

1 with measured affinity, of 24 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethynyl]benzoic acid	1586852: Displacement of DC271 from CRABP2 (unknown origin) by fluorescence assay	kd	0.1600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects folding, increases activity, increases expression, affects cotreatment, affects binding (+5 more)	13
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	6
sodium arsenite	increases expression, affects methylation, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
Vitamin A	increases expression, increases reaction	3
bisphenol A	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Adapalene	increases expression	2
Resveratrol	increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Alitretinoin	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Copper	decreases expression, affects binding	2
Dactinomycin	affects cotreatment, increases expression, increases secretion	2
Tobacco Smoke Pollution	affects expression	2
Aflatoxin B1	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
4-oxoretinoic acid	increases expression	1
apocarotenal	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
methylselenic acid	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
titanium dioxide	decreases methylation, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2182118	Binding	Binding affinity to Flag-tagged cIAP1/CRABP2 expressed in human IMR32 cells assessed as reduction in MycN level at 1 to 10 uM after 48 hrs by Western blot analysis	Development of target protein-selective degradation inducer for protein knockdown. — Bioorg Med Chem

Clinical trials (associated diseases)

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