RBP5

Summary

RBP5 (retinol binding protein 5, HGNC:15847) is a protein-coding gene on chromosome 12p13.31, encoding Retinol-binding protein 5 (P82980). Intracellular transport of retinol.

The protein encoded by this gene is a cellular retinol-binding protein expressed highly in kidney and liver. Down-regulation of the encoded protein in hepatocellular carcinoma was associated with large tumor size and poor patient survival rates.

Source: NCBI Gene 83758 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_031491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15847
Approved symbol	RBP5
Name	retinol binding protein 5
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CRBPIII, CRBP3, CRBP-III
Ensembl gene	ENSG00000139194
Ensembl biotype	protein_coding
OMIM	611866
Entrez	83758

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000266560, ENST00000542370, ENST00000542784, ENST00000543045, ENST00000619522, ENST00000890521, ENST00000890522

RefSeq mRNA: 2 — MANE Select: NM_031491 NM_001329454, NM_031491

CCDS: CCDS8574

Canonical transcript exons

ENST00000266560 — 4 exons

Exon	Start	End
ENSE00000937011	7128240	7128418
ENSE00001328243	7123686	7124174
ENSE00002287871	7128703	7128889
ENSE00003636441	7124629	7124730

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 99.02.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7690 / max 372.8658, expressed in 272 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129253	2.5066	221
129254	0.2625	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	99.02	gold quality
right lobe of liver	UBERON:0001114	98.85	gold quality
liver	UBERON:0002107	98.27	gold quality
spleen	UBERON:0002106	96.65	gold quality
lymph node	UBERON:0000029	95.70	gold quality
kidney	UBERON:0002113	95.61	gold quality
metanephros cortex	UBERON:0010533	95.31	gold quality
vermiform appendix	UBERON:0001154	91.98	gold quality
cortex of kidney	UBERON:0001225	91.48	gold quality
mucosa of transverse colon	UBERON:0004991	86.88	gold quality
mucosa of stomach	UBERON:0001199	86.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.98	gold quality
myometrium	UBERON:0001296	85.96	gold quality
smooth muscle tissue	UBERON:0001135	85.92	gold quality
small intestine	UBERON:0002108	85.88	gold quality
gall bladder	UBERON:0002110	85.29	gold quality
body of uterus	UBERON:0009853	85.20	gold quality
colonic epithelium	UBERON:0000397	85.00	gold quality
left adrenal gland cortex	UBERON:0035825	84.70	gold quality
endocervix	UBERON:0000458	84.52	gold quality
duodenum	UBERON:0002114	84.33	gold quality
left adrenal gland	UBERON:0001234	84.18	gold quality
right adrenal gland	UBERON:0001233	83.93	gold quality
rectum	UBERON:0001052	83.57	gold quality
right ovary	UBERON:0002118	83.55	gold quality
adrenal gland	UBERON:0002369	83.53	gold quality
tonsil	UBERON:0002372	83.17	gold quality
uterine cervix	UBERON:0000002	82.67	gold quality
right adrenal gland cortex	UBERON:0035827	82.56	gold quality
left uterine tube	UBERON:0001303	82.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

33 targeting RBP5, 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-1252-5P	100.00	69.80	2774
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-631	97.05	66.93	602
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-7846-3P	96.92	65.18	51
HSA-MIR-6894-3P	96.73	65.64	798
HSA-MIR-6815-5P	96.05	65.55	662

Literature-anchored findings (GeneRIF, showing 1)

• Our study revealed that RBP5 down-regulation in HCC was associated with aggressive tumor features, suggesting an (PMID:17497168)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbp7a	ENSDARG00000091906
danio_rerio	rbp5	ENSDARG00000101481
drosophila_melanogaster	fabp	FBGN0037913
caenorhabditis_elegans		WBGENE00002259
caenorhabditis_elegans		WBGENE00002260

Paralogs (15): RBP2 (ENSG00000114113), RBP1 (ENSG00000114115), FABP3 (ENSG00000121769), 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 5 — P82980 (reviewed: P82980)

Alternative names: Cellular retinol-binding protein III, HRBPiso

All UniProt accessions (3): A0A0B4J233, P82980, F5H2Q2

UniProt curated annotations — full annotation on UniProt →

Function. Intracellular transport of retinol.

Subcellular location. Cytoplasm.

Tissue specificity. Higher expression in adult kidney and liver and to a lesser extent in adult and fetal spleen, adult lymph nodes and appendix, and fetal liver and kidney. Strongly decreased in hepatocellular carcinoma tissues (at protein level).

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.

RefSeq proteins (2): NP_001316383, NP_113679* (*=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 (18 total): strand 10, sequence variant 3, turn 2, helix 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9BCB	X-RAY DIFFRACTION	1.45
1GGL	X-RAY DIFFRACTION	2.31
6E5W	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P82980-F1	96.78	0.94

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): ATF_B, GCANCTGNY_MYOD_Q6, SP3_Q3, GGGTGGRR_PAX4_03, GOBP_ORGANIC_ACID_TRANSPORT, CREB_Q4, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, TGCTGAY_UNKNOWN, TCF11_01, GOBP_ORGANIC_ANION_TRANSPORT, CREB_Q2_01, LYF1_01, ATF4_Q2, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT

GO Biological Process (1): fatty acid transport (GO:0015908)

GO Molecular Function (6): retinoid binding (GO:0005501), fatty acid binding (GO:0005504), retinal binding (GO:0016918), retinol binding (GO:0019841), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid binding	2
vitamin binding	2
binding	2
cellular anatomical structure	2
lipid transport	1
monocarboxylic acid transport	1
isoprenoid binding	1
lipid binding	1
monocarboxylic acid binding	1
alcohol binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBP5	URI1	O94763	685
RBP5	ASH2L	Q9UBL3	532
RBP5	WDR5	P61964	523
RBP5	DPY30	Q9C005	523
RBP5	RUVBL2	Q9Y230	509
RBP5	RUVBL1	P82276	506
RBP5	POLR2E	P19388	479
RBP5	LRAT	O95237	447
RBP5	POLR2A	P24928	435
RBP5	STRA6	Q9BX79	432
RBP5	PMS2P11	Q13670	414
RBP5	UPK1A	O00322	402
RBP5	UPK2	O00526	395
RBP5	RDH5	Q92781	381
RBP5	TAF1	P21675	373

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CCNDBP1	RBP5	psi-mi:“MI:0915”(physical association)	0.560
AGR2	RBP5	psi-mi:“MI:0915”(physical association)	0.560
NR0B2	RBP5	psi-mi:“MI:0915”(physical association)	0.370
RBP5	ABCC5	psi-mi:“MI:0915”(physical association)	0.370
RBP5	AGR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): RBP5 (Two-hybrid), RBP5 (Reconstituted Complex), RBP5 (Two-hybrid), RBP5 (Affinity Capture-MS), RBP5 (Two-hybrid), RBP5 (Two-hybrid)

ESM2 similar proteins: A6NFH5, B7SUM8, O01812, O01814, O02323, O02324, O08716, O45035, P02693, P0C241, P0C6G6, P10289, P12104, P24526, P29498, P41496, P41509, P50119, P51161, P51162, P51880, P55050, P55054, P80226, P80856, P81653, P82289, P82708, P82980, P83409, Q02970, Q0Z7S8, Q17284, Q1AMT3, Q23092, Q3T0Z2, Q45KW7, Q56JX9, Q5RBM7, Q7M4G0

Diamond homologs: A0A0K0MJ13, A0A0K0MJN3, A6NFH5, A6YLM6, A8MUU1, B7SUM8, C4N147, O01812, O01814, O02323, O02324, O02772, O08716, O13008, O15540, O42386, O45035, O76821, O97788, P02689, P02690, P02691, P02693, P02694, P02696, P04117, P05413, P06768, P07483, P09455, P0C241, P0C6G6, P0DM59, P10790, P11404, P12104, P15090, P22935, P24526, P29373

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

485 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7128235:TGTA:T	donor_loss	1.0000
12:7128236:GTAC:G	donor_loss	1.0000
12:7128237:TACCT:T	donor_loss	1.0000
12:7128238:A:C	donor_loss	1.0000
12:7128239:C:G	donor_loss	1.0000
12:7128701:A:AC	donor_gain	1.0000
12:7128702:C:CC	donor_gain	1.0000
12:7128705:A:AC	donor_gain	1.0000
12:7128705:AGGG:A	donor_gain	1.0000
12:7128706:G:C	donor_gain	1.0000
12:7124173:TCCT:T	acceptor_loss	0.9800
12:7124174:CCTG:C	acceptor_loss	0.9800
12:7124175:CTG:C	acceptor_loss	0.9800
12:7124645:C:CA	donor_gain	0.9800
12:7124683:C:A	donor_gain	0.9800
12:7124175:C:CC	acceptor_gain	0.9600
12:7124623:ATTT:A	donor_loss	0.9500
12:7124624:TTTAC:T	donor_loss	0.9500
12:7124625:TTACC:T	donor_loss	0.9500
12:7124626:TA:T	donor_loss	0.9500
12:7124627:ACCAG:A	donor_loss	0.9500
12:7124628:CCA:C	donor_loss	0.9500
12:7124731:C:CC	acceptor_gain	0.9500
12:7128239:CCTGG:C	donor_gain	0.9500
12:7124644:T:A	donor_gain	0.9400
12:7124622:CATTT:C	donor_loss	0.9300
12:7124728:GGTC:G	acceptor_loss	0.9300
12:7124730:TC:T	acceptor_loss	0.9300
12:7124731:C:CA	acceptor_loss	0.9300
12:7124173:TC:T	acceptor_gain	0.9200

AlphaMissense

883 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7128279:A:C	F71L	0.987
12:7128279:A:T	F71L	0.987
12:7128281:A:G	F71L	0.987
12:7128297:A:C	F65L	0.985
12:7128297:A:T	F65L	0.985
12:7128299:A:G	F65L	0.985
12:7124136:G:C	F131L	0.982
12:7124136:G:T	F131L	0.982
12:7124138:A:G	F131L	0.982
12:7128324:G:C	S56R	0.976
12:7128324:G:T	S56R	0.976
12:7128326:T:G	S56R	0.976
12:7128369:C:A	K41N	0.974
12:7128369:C:G	K41N	0.974
12:7124664:A:G	W107R	0.973
12:7124664:A:T	W107R	0.973
12:7124689:C:A	Q98H	0.963
12:7124689:C:G	Q98H	0.963
12:7124662:C:A	W107C	0.962
12:7124662:C:G	W107C	0.962
12:7124669:C:G	R105P	0.961
12:7124716:C:A	W89C	0.955
12:7124716:C:G	W89C	0.955
12:7128400:C:G	R31P	0.953
12:7128250:C:G	R81P	0.952
12:7124695:A:C	C96W	0.951
12:7124723:A:T	V87E	0.948
12:7128751:A:C	Y9D	0.946
12:7124630:A:G	L118P	0.944
12:7124137:A:G	F131S	0.941

dbSNP variants (sampled 300 via entrez): RS1000269680 (12:7120097 GC>G), RS1000324504 (12:7126381 A>G), RS1000461829 (12:7126598 A>G), RS1000528676 (12:7120359 T>G), RS1000595062 (12:7121725 A>G,T), RS1000660048 (12:7124872 C>G), RS1000796982 (12:7125169 A>G), RS1000951109 (12:7126545 G>A,C), RS1001024796 (12:7126244 A>G), RS1001459287 (12:7126675 T>C), RS1001575350 (12:7115833 C>T), RS1001593606 (12:7126998 T>A), RS1001793147 (12:7125309 G>A), RS1002107623 (12:7120485 T>C), RS1002296911 (12:7120750 A>C)

Disease associations

OMIM: gene MIM:611866 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_196	Night sleep phenotypes	5.000000e-06
GCST010002_206	Refractive error	3.000000e-62
GCST90002400_74	Plateletcrit	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
Acetaminophen	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Perfume	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Antirheumatic Agents	decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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