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GeneE
28 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RBP4
retinol binding protein 4
Chromosome 10 Β· 10q23.33
NCBI Gene: 5950Ensembl: ENSG00000138207.15HGNC: HGNC:9922UniProt: P02753
397PubMed Papers
22Diseases
0Drugs
18Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
GO:0005615retinol bindingprotein bindingmaintenance of gastrointestinal epitheliumprogressive retinal dystrophy due to retinol transport defectmicrophthalmia, isolated, with coloboma 10microphthalmiamicrophthalmia, isolated, with coloboma
✦AI Summary

RBP4 (retinol-binding protein 4) is a lipocalin family member that serves as the primary circulating carrier for vitamin A, mediating retinol transport from hepatic stores to peripheral tissues 1. The protein transfers bound retinol to STRA6, facilitating cellular uptake across membranes 2. Beyond its classical transport function, RBP4 functions as an adipokine with pleiotropic metabolic effects 3. Elevated serum RBP4 correlates with insulin resistance and type 2 diabetes development; mechanistically, RBP4 stimulates adipocyte lipolysis and macrophage TNFΞ± production, impairing insulin-mediated suppression of free fatty acid release 4. Circulating RBP4 levels are significantly elevated in gestational diabetes mellitus across all pregnancy trimesters, potentially serving as a biomarker 5. In ocular pathology, macrophage-derived RBP4 promotes pathological neovascularization in age-related macular degeneration and diabetic retinopathy through VEGFR2-dependent endothelial sprouting 6. RBP4 elevation associates with psoriasis and cardiovascular disease; however, evidence suggests potential cardioprotective effects via vasodilation and reduced platelet activation in certain contexts 78. Clinical significance includes diagnostic potential for liver damage and cancer prognosis 9, though RBP4's role in cardiovascular disease remains controversial.

Sources cited
1
RBP4 mediates retinol transport in blood plasma
PMID: 5541771
2
RBP4 transfers retinol to STRA6 for cellular membrane transport
PMID: 22665496
3
RBP4 is an adipokine linked to obesity, insulin resistance, and type 2 diabetes
PMID: 21835764
4
RBP4 stimulates adipocyte lipolysis and impairs insulin-mediated suppression of free fatty acids in obesity
PMID: 32167208
5
Elevated RBP4 levels are associated with gestational diabetes mellitus across pregnancy trimesters
PMID: 38532976
6
Macrophage-derived RBP4 promotes pathological neovascularization in age-related macular degeneration and diabetic retinopathy
PMID: 38129891
7
Increased RBP4 shows vasodilatory and cardioprotective effects in a model of anti-atherosclerotic defense
PMID: 24739026
8
RBP4 levels are elevated in psoriasis and associated with cardiovascular disease
PMID: 30193612
9
RBP4 expression correlates with liver damage and plays a role in cancer diagnosis and prognosis
PMID: 34889026
Disease Associationsβ“˜22
progressive retinal dystrophy due to retinol transport defectOpen Targets
0.69Moderate
microphthalmia, isolated, with coloboma 10Open Targets
0.64Moderate
microphthalmiaOpen Targets
0.50Moderate
microphthalmia, isolated, with colobomaOpen Targets
0.46Moderate
Retinal dystrophyOpen Targets
0.42Moderate
Bilateral microphthalmosOpen Targets
0.41Moderate
colobomaOpen Targets
0.40Weak
retinitis pigmentosaOpen Targets
0.39Weak
congenital stationary night blindnessOpen Targets
0.38Weak
reticular dystrophy of the retinal pigment epitheliumOpen Targets
0.37Weak
open-angle glaucomaOpen Targets
0.36Weak
genetic disorderOpen Targets
0.34Weak
diabetic ketoacidosisOpen Targets
0.32Weak
AnophthalmiaOpen Targets
0.27Weak
anterior segment dysgenesisOpen Targets
0.27Weak
Ocular anterior segment dysgenesisOpen Targets
0.27Weak
Unilateral microphthalmosOpen Targets
0.27Weak
Abnormality of the eyeOpen Targets
0.26Weak
glioblastoma multiformeOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
Microphthalmia/Coloboma 10UniProt
Retinal dystrophy, iris coloboma, and comedogenic acne syndromeUniProt
Pathogenic Variants18
NM_006744.4(RBP4):c.358G>C (p.Asp120His)Likely pathogenic
Congenital ocular coloboma
β˜…β˜†β˜†β˜†2022β†’ Residue 120
NM_006744.4(RBP4):c.217G>A (p.Ala73Thr)Pathogenic
Microphthalmia, isolated, with coloboma 10|Bilateral microphthalmos
β˜…β˜†β˜†β˜†2022β†’ Residue 73
NM_006744.4(RBP4):c.218C>T (p.Ala73Val)Likely pathogenic
Anophthalmia
β˜…β˜†β˜†β˜†2022β†’ Residue 73
NM_006744.4(RBP4):c.358G>T (p.Asp120Tyr)Likely pathogenic
Bilateral microphthalmos
β˜…β˜†β˜†β˜†2022β†’ Residue 120
NM_006744.4(RBP4):c.383A>G (p.Asp128Gly)Likely pathogenic
Anterior segment dysgenesis
β˜…β˜†β˜†β˜†2022β†’ Residue 128
NM_006744.4(RBP4):c.244_248+2delLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_006744.4(RBP4):c.111+1G>CPathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_006744.4(RBP4):c.129C>G (p.Tyr43Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 43
NM_006744.4(RBP4):c.355+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_006744.4(RBP4):c.324_349del (p.Tyr108_Lys117delinsTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 108
NM_006744.4(RBP4):c.67C>T (p.Arg23Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 23
NM_006744.4(RBP4):c.569-1G>ALikely pathogenic
Microphthalmia, isolated, with coloboma 10
β˜…β˜†β˜†β˜†2020
NM_006744.4(RBP4):c.526G>T (p.Glu176Ter)Pathogenic
Progressive retinal dystrophy due to retinol transport defect|Retinal dystrophy
β˜…β˜†β˜†β˜†2020β†’ Residue 176
NM_006744.4(RBP4):c.353G>A (p.Gly118Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 118
NM_006744.4(RBP4):c.223G>A (p.Ala75Thr)Likely pathogenic
Microphthalmia, isolated, with coloboma 10|Inborn genetic diseases
β˜…β˜†β˜†β˜†2017β†’ Residue 75
NM_006744.4(RBP4):c.38_56del (p.Leu13fs)Likely pathogenic
Retinal dystrophy
β˜†β˜†β˜†β˜†2022β†’ Residue 13
NM_006744.4(RBP4):c.248+1G>ALikely pathogenic
Abnormality of the eye
β˜†β˜†β˜†β˜†2015
NM_006744.4(RBP4):c.111+1G>APathogenic
Progressive retinal dystrophy due to retinol transport defect
β˜†β˜†β˜†β˜†2012
View on ClinVar β†—
Related Genes
GCProtein interaction100%ALBProtein interaction100%STRA6Protein interaction98%ADIPOQProtein interaction97%LEPProtein interaction93%RBP1Protein interaction91%
Tissue Expression6 tissues
Liver
100%
Brain
0%
Lung
0%
Heart
0%
Bone Marrow
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
RBP4GCALBSTRA6ADIPOQLEPRBP1
PROTEIN STRUCTURE
Preparing viewer…
PDB5NU2 Β· 1.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.57Moderately Constrained
pLIβ“˜
0.87Intermediate
Observed/Expected LoF0.33 [0.20–0.57]
RankingsWhere RBP4 stands among ~20K protein-coding genes
  • #743of 20,598
    Most Researched397 Β· top 5%
  • #2,264of 5,498
    Most Pathogenic Variants18
  • #3,801of 17,882
    Most Constrained (LOEUF)0.57 Β· top quartile
Genes detectedRBP4
Sources retrieved28 papers
Response timeβ€”
πŸ“„ Sources
28β–Ό
1
Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.
PMID: 38129891
J Neuroinflammation Β· 2023
1.00
2
[Psoriasis,Cardiovascular Disease,and Adipokines].
PMID: 30193612
Zhongguo Yi Xue Ke Xue Yuan Xue Bao Β· 2018
0.90
3
Assessing the Impact of Bariatric Surgery on Retinol-Binding Protein 4 (RBP4): A Systematic Review and Meta-Analysis.
PMID: 38451368
Obes Surg Β· 2024
0.88
4
RBP4: a controversial adipokine.
PMID: 21835764
Eur J Endocrinol Β· 2011
0.80
5
Retinol binding protein 4 restricts PCV2 replication via selective autophagy degradation of viral ORF1 protein.
PMID: 39500783
Commun Biol Β· 2024
0.76