Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCY4D6B)

• DOT Name: Retinaldehyde-binding protein 1 (RLBP1)
• Synonyms: Cellular retinaldehyde-binding protein
• Gene Name: RLBP1
• Related Disease:
  Bothnia retinal dystrophy
  RLBP1-related retinopathy
  Age-related macular degeneration
  Cone dystrophy
  Familial adenomatous polyposis
  Fundus albipunctatus
  Inherited retinal dystrophy
  Neoplasm
  Newfoundland cone-rod dystrophy
  Retinitis
  Retinopathy
  Schizophrenia
  Uveitis
  Retinitis pigmentosa
  Retinitis punctata albescens
  Osteoarthritis
• UniProt ID: RLBP1_HUMAN
• PDB ID: 3HX3; 3HY5; 4CIZ; 4CJ6
• Pfam ID: PF00650 ; PF03765
• Sequence:
  MSEGVGTFRMVPEEEQELRAQLEQLTTKDHGPVFGPCSQLPRHTLQKAKDELNEREETRE
  EAVRELQEMVQAQAASGEELAVAVAERVQEKDSGFFLRFIRARKFNVGRAYELLRGYVNF
  RLQYPELFDSLSPEAVRCTIEAGYPGVLSSRDKYGRVVMLFNIENWQSQEITFDEILQAY
  CFILEKLLENEETQINGFCIIENFKGFTMQQAASLRTSDLRKMVDMLQDSFPARFKAIHF
  IHQPWYFTTTYNVVKPFLKSKLLERVFVHGDDLSGFYQEIDENILPSDFGGTLPKYDGKA
  VAEQLFGPQAQAENTAF
• Function: 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'.
• Tissue Specificity: Retina and pineal gland. Not present in photoreceptor cells but is expressed abundantly in the adjacent retinal pigment epithelium (RPE) and in the Mueller glial cells of the retina.
• Reactome Pathway:
  Retinoid cycle disease events (R-HSA-2453864)
  The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)
  The retinoid cycle in cones (daylight vision) (R-HSA-2187335)
• BioCyc Pathway: MetaCyc:ENSG00000140522-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bothnia retinal dystrophy	DISYEI1M	Definitive	Autosomal recessive	[1]
RLBP1-related retinopathy	DIS5F8BY	Definitive	Autosomal recessive	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[3]
Cone dystrophy	DIS7SAZZ	Strong	Genetic Variation	[4]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[4]
Fundus albipunctatus	DISNICY6	Strong	Autosomal recessive	[5]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Newfoundland cone-rod dystrophy	DIS4A0KN	Strong	Autosomal recessive	[5]
Retinitis	DISRWZEG	Strong	Genetic Variation	[8]
Retinopathy	DISB4B0F	Strong	Genetic Variation	[9]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[10]
Uveitis	DISV0RYS	Strong	Biomarker	[11]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[12]
Retinitis punctata albescens	DISVJAI4	Supportive	Autosomal dominant	[13]
Osteoarthritis	DIS05URM	Limited	Biomarker	[14]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Retinaldehyde-binding protein 1 (RLBP1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Retinaldehyde-binding protein 1 (RLBP1).	[17]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Retinaldehyde-binding protein 1 (RLBP1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Retinaldehyde-binding protein 1 (RLBP1).	[18]

References

• [1] Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1. Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3172-7. doi: 10.1167/iovs.07-1664. Epub 2008 Mar 14.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration.Nat Genet. 2019 Apr;51(4):606-610. doi: 10.1038/s41588-019-0351-9. Epub 2019 Feb 11.
• [4] A homozygous frameshift mutation in LRAT causes retinitis punctata albescens.Ophthalmology. 2012 Sep;119(9):1899-906. doi: 10.1016/j.ophtha.2012.02.037. Epub 2012 May 3.
• [5] Visual cycle impairment in cellular retinaldehyde binding protein (CRALBP) knockout mice results in delayed dark adaptation. Neuron. 2001 Mar;29(3):739-48. doi: 10.1016/s0896-6273(01)00248-3.
• [6] Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens.Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4719-24. doi: 10.1167/iovs.05-1488.
• [7] RALBP1 regulates oral cancer cells via Akt and is a novel target of miR-148a-3p and miR-148b-3p.J Oral Pathol Med. 2019 Nov;48(10):919-928. doi: 10.1111/jop.12936. Epub 2019 Aug 18.
• [8] Novel mutation in RLBP1 gene in a Japanese patient with retinitis punctata albescens.Am J Ophthalmol. 2005 Jun;139(6):1133-5. doi: 10.1016/j.ajo.2004.12.011.
• [9] Phenotype variations of retinal dystrophies caused by mutations in the RLBP1 gene.Acta Ophthalmol. 2015 Jun;93(4):e281-6. doi: 10.1111/aos.12573. Epub 2014 Nov 27.
• [10] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [11] CRALBP is a highly prevalent autoantigen for human autoimmune uveitis.Clin Dev Immunol. 2007;2007:39245. doi: 10.1155/2007/39245.
• [12] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [13] Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens. Invest Ophthalmol Vis Sci. 1999 Apr;40(5):1000-4.
• [14] A retinal-binding protein mediates olfactory attraction in the migratory locusts.Insect Biochem Mol Biol. 2019 Nov;114:103214. doi: 10.1016/j.ibmb.2019.103214. Epub 2019 Aug 20.
• [15] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [16] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [17] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.