Online Mendelian Inheritance in Man (OMIM)
- ️Mon Aug 03 2015
* 605748
BETA-CAROTENE OXYGENASE 1; BCO1
Alternative titles; symbols
BETA-CAROTENE 15,15-PRIME-MONOOXYGENASE 1; BCMO1
BETA-CAROTENE 15,15-PRIME-DIOXYGENASE; BCDO
BETA-CAROTENE 15,15-PRIME OXYGENASE 1
HGNC Approved Gene Symbol: BCO1
Cytogenetic location: 16q23.2 Genomic coordinates (GRCh38) : 16:81,238,689-81,291,142 (from NCBI)
Gene-Phenotype Relationships
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 16q23.2 | ?Hypercarotenemia and vitamin A deficiency, autosomal dominant | 115300 | Autosomal dominant | 3 |
TEXT
Description
Vitamin A metabolism is important for vital processes such as vision, embryonic development, cell differentiation, and membrane and skin protection. Beta-carotene 15,15-prime-monooxygenase (EC 1.13.11.21) is a key enzyme in beta-carotene metabolism to vitamin A.
Cloning and Expression
Wyss et al. (2000) cloned chicken Bcdo from a duodenal expression library. They demonstrated that chicken Bcdo is a cytoplasmic enzyme that specifically cleaves beta-carotene at the 15,15-prime-double bond. Von Lintig and Vogt (2000) cloned Drosophila Bcdo, which encodes a protein that shares 36.7% sequence identity with the bovine retinal pigment epithelium-specific gene Rpe65 (180069). They found that recombinant Drosophila Bcdo catalyzes centric cleavage of beta-carotene, resulting in the formation of 2 molecules of retinal. RT-PCR detected Bcdo expression exclusively in Drosophila head. Yan et al. (2001) cloned human BCMO1, which they called BCDO, from a retinal pigment epithelium (RPE) cDNA library by screening with a PCR probe generated from a subtracted bovine RPE cDNA library. By EST database searching, they also identified the mouse homolog. The deduced 547-amino acid human protein, which has a calculated molecular mass of 62 kD, shares 37% sequence identity with RPE65 (180069), 67% with chicken Bcdo, and 83% with mouse Bcdo. By Northern blot analysis, Yan et al. (2001) identified a 2.4-kb transcript in human RPE, but not in mRNA from whole retina or in any other tissues tested. By RT-PCR, they found expression in kidney, testis, liver, brain, small intestine, and colon as well as in RPE.
Gene Structure
Yan et al. (2001) determined that the BCMO1 gene contains 11 exons spanning approximately 20 kb of genomic DNA.
Mapping
Using a combination of somatic cell and radiation hybrid analysis, Yan et al. (2001) mapped the BCMO1 gene to chromosome 16q21-q23.
Gene Function
Yan et al. (2001) found that recombinant BCDO expressed in sf9 insect cells was specific toward beta-carotene in biochemical assays.
Molecular Genetics
In a patient with hypercarotenemia and vitamin A deficiency (HCVAD; 115300), Lindqvist et al. (2007) identified a heterozygous mutation in the BCMO1 gene (605748.0001).
Animal Model
Widjaja-Adhi et al. (2015) characterized zeaxanthin uptake and metabolism in single and compound mutant mice lacking Bco2 (611740), Scarb1 (601040), Isx (612019), and/or Bco1. They found that the membrane protein Scarb1 was required for intestinal xanthophyll uptake. The transcription factor Isx downregulated Scarb1 and Bco1 expression by binding to a core DNA element in their promoters. Bco1 was required for xanthophyll absorption in liver and eye. The studies identified Bco1 and Bco2 as the major metabolizing enzymes for beta-carotene and zeaxanthin, respectively, and showed that Bco1-dependent retinoid signaling induced Isx expression in a negative-feedback loop.
ALLELIC VARIANTS 1 Selected Example):
.0001 HYPERCAROTENEMIA AND VITAMIN A DEFICIENCY, AUTOSOMAL DOMINANT (1 patient)
BCO1, THR170MET
SNP: rs119478057,
gnomAD: rs119478057,
ClinVar: RCV000005038, RCV002247250, RCV003924801
In a patient with hypercarotenemia and vitamin A deficiency (HCVAD; 115300) who was previously reported by Sharvill (1970), Lindqvist et al. (2007) identified a heterozygous C-to-T transition in exon 5 of the BCMO1 gene, resulting in a thr170-to-met (T170M) substitution in a highly conserved residue. In vitro functional expression studies showed that the mutant protein had about 90% decreased enzyme activity compared to wildtype. There was no evidence for a dominant-negative effect. The mutation was not identified in 60 control chromosomes. The findings were consistent with a loss-of-function mutation resulting in haploinsufficiency.
REFERENCES
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Lindqvist, A., Sharvill, J., Sharvill, D. E., Andersson, S. Loss-of-function mutation in carotenoid 15,15-prime-monooxygenase identified in a patient with hypercarotenemia and hypovitaminosis A. J. Nutr. 137: 2346-2350, 2007. [PubMed: 17951468] [Full Text: https://doi.org/10.1093/jn/137.11.2346]
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Sharvill, D. E. Familial hypercarotinaemia and hypovitaminosis A. Proc. Roy. Soc. Med. 63: 605-606, 1970. [PubMed: 5453458]
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von Lintig, J., Vogt, K. Filling the gap in vitamin A research: molecular identification of an enzyme cleaving beta-carotene to retinal. J. Biol. Chem. 275: 11915-11920, 2000. [PubMed: 10766819] [Full Text: https://doi.org/10.1074/jbc.275.16.11915]
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Widjaja-Adhi, M. A. K., Lobo, G. P., Golczak, M., Von Lintig, J. A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption. Hum. Molec. Genet. 24: 3206-3219, 2015. [PubMed: 25701869] [Full Text: https://doi.org/10.1093/hmg/ddv072]
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Wyss, A., Wirtz, G., Woggon, W.-D., Brugger, R., Wyss, M., Friedlein, A., Bachmann, H., Hunziker, W. Cloning and expression of beta,beta-carotene 15,15-prime-dioxygenase. Biochem. Biophys. Res. Commun. 271: 334-336, 2000. [PubMed: 10799297] [Full Text: https://doi.org/10.1006/bbrc.2000.2619]
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Yan, W., Jang, G.-F., Haeseleer, F., Esumi, N., Chang, J., Kerrigan, M., Campochiaro, M., Campochiaro, P., Palczewski, K., Zack, D. J. Cloning and characterization of a human beta,beta-carotene-15,15-prime dioxygenase that is highly expressed in the retinal pigment epithelium. Genomics 72: 193-202, 2001. [PubMed: 11401432] [Full Text: https://doi.org/10.1006/geno.2000.6476]
Contributors:
Patricia A. Hartz - updated : 8/3/2015
Cassandra L. Kniffin - updated : 3/6/2009
Patricia A. Hartz - updated : 4/9/2002
Creation Date:
Dawn Watkins-Chow : 3/20/2001
Edit History:
carol : 01/05/2018
carol : 01/04/2018
carol : 01/04/2018
mgross : 08/06/2015
mcolton : 8/3/2015
carol : 7/1/2013
carol : 3/9/2009
ckniffin : 3/6/2009
wwang : 1/18/2008
carol : 4/9/2002
carol : 3/22/2001