The reference OMIM entry for this protein is 180250

Retinol-binding protein 4; rbp4
Retinol-binding protein, plasma

DESCRIPTION

Retinol-binding protein (RBP) is a monomeric-binding protein of 21 kD that specifically transports retinol, the alcoholic form of vitamin A, in plasma from its main store site, the liver, to target cells. RBP circulates almost entirely bound to thyroxine-binding transthyretin (TTR; 176300) (summary by Folli et al., 2005).

CLONING

Rask et al. (1987) reported the complete amino acid sequence of serum retinol-binding protein. Pervaiz and Brew (1985) found homology of human serum RBP to bovine beta-lactoglobulin and to protein HCP.

MAPPING

Using a cDNA probe for RBP4, Rocchi et al. (1989) performed in situ hybridization and Southern blot analysis of genomic DNA from somatic cell hybrids to map the RBP4 gene to 10q23-q24. Gray et al. (1995) found that the RBP4 gene resides just centromeric of the cluster of CYP2C genes (124020) on 10q24. By the study of recombinant inbred strains, Chainani et al. (1991) showed that the mouse Rbp4 locus is closely linked and just proximal to the locus for phenobarbital-inducible cytochrome P450-2c (Cyp-2c) at the distal end of chromosome 19.

MOLECULAR GENETICS

- Retinal Dystrophy, Iris Coloboma, and Comedogenic Acne Syndrome In 2 German sisters with night blindness and retinal dystrophy who had no detectable serum RBP, retinol levels less than 20% of normal, and normal retinyl esters (RDCCAS; 615147), Seeliger et al. (1999) identified compound heterozygosity for missense mutations in the RBP4 gene (180250.0001 and 180250.0002). Both sisters also displayed severe comedogenic acne and widespread follicular keratosis. Using exome capture and next-generation sequencing in a brother and sister with early-onset progressive severe retinal dystrophy, who were born of second-cousin parents, Cukras et al. (2012) identified homozygosity for a splice site mutation in the RBP4 gene (180250.0003). Lack of other classic symptoms of vitamin A deficiency in these patients suggested that some dietary vitamin A was being delivered to organs independently of RBP4, but that RBP4 was required to deliver sufficient levels of vitamin A to prevent retinal degeneration. Additional features included iris coloboma in the brother and persistent acne into the sixth decade of life in the sister. - Microphthalmia, Isolated, with Coloboma 10 In a 7-generation family segregating autosomal dominant microphthalmia or clinical anophthalmia and/or coloboma (MCOPCB10; 616428) mapping to chromosome 10q23, Chou et al. (2015) analyzed 3 genes in the critical region that have roles in vitamin A transport and identified a heterozygous missense mutation in the RBP4 gene (A75T; 180250.0004) in affected individuals and obligate carriers. Screening of DNA samples from 75 unrelated microphthalmia/coloboma cases revealed another missense mutation (A73T; 180250.0005) in 2 patients. Functional analysis demonstrated that both mutant retinol-binding proteins (RBPs) bind the STRA6 (610745) receptor with much higher affinity than wildtype yet carry little or no vitamin A. Consistent with these findings, all 3 A75T heterozygous carriers who were tested had fasting serum vitamin A levels below normal limits, and plasma retinol fluorescence was also reduced. Maternal penetrance was significantly greater than paternal penetrance (0.7 vs 0.1). Chou et al. (2015) therefore suggested that when the RBP4 mutation is maternally transmitted, there is decreased vitamin A delivery both at the placenta, involving maternal- ... More on the omim web site

Subscribe to this protein entry history

Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 180250 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).