4ciz

Structural highlights

Disease

[RLBP1_HUMAN] Defects in RLBP1 are a cause of retinitis pigmentosa autosomal recessive (ARRP) [MIM:268000]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.^[1] Defects in RLBP1 are the cause of Bothnia retinal dystrophy (BRD) [MIM:607475]; also known as Vasterbotten dystrophy. Affected individuals show night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration.^[2] Defects in RLBP1 are the cause of rod-cone dystrophy Newfoundland (NFRCD) [MIM:607476]. NFRCD is a retinal dystrophy reminiscent of retinitis punctata albescens but with a substantially lower age at onset and more-rapid and distinctive progression. Rod-cone dystrophies results from initial loss of rod photoreceptors, later followed by cone photoreceptors loss.^[3] Defects in RLBP1 are a cause of retinitis punctata albescens (RPA) [MIM:136880]. A rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments.

Function

[RLBP1_HUMAN] Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'.^[4]

References

1. ↑ Maw MA, Kennedy B, Knight A, Bridges R, Roth KE, Mani EJ, Mukkadan JK, Nancarrow D, Crabb JW, Denton MJ. Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa. Nat Genet. 1997 Oct;17(2):198-200. PMID:9326942 doi:10.1038/ng1097-198
2. ↑ Burstedt MS, Sandgren O, Holmgren G, Forsman-Semb K. Bothnia dystrophy caused by mutations in the cellular retinaldehyde-binding protein gene (RLBP1) on chromosome 15q26. Invest Ophthalmol Vis Sci. 1999 Apr;40(5):995-1000. PMID:10102298
3. ↑ Eichers ER, Green JS, Stockton DW, Jackman CS, Whelan J, McNamara JA, Johnson GJ, Lupski JR, Katsanis N. Newfoundland rod-cone dystrophy, an early-onset retinal dystrophy, is caused by splice-junction mutations in RLBP1. Am J Hum Genet. 2002 Apr;70(4):955-64. Epub 2002 Feb 26. PMID:11868161 doi:S0002-9297(07)60302-4
4. ↑ He X, Lobsiger J, Stocker A. Bothnia dystrophy is caused by domino-like rearrangements in cellular retinaldehyde-binding protein mutant R234W. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18545-50. Epub 2009 Oct 21. PMID:19846785
5. ↑ Bolze CS, Helbling RE, Owen RL, Pearson AR, Pompidor G, Dworkowski F, Fuchs MR, Furrer J, Golczak M, Palczewski K, Cascella M, Stocker A. Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-cis-Retinal Isomerase Activity. J Am Chem Soc. 2013 Dec 20. PMID:24328211 doi:http://dx.doi.org/10.1021/ja411366w