Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP65YD7)

• DOT Name: RAB6-interacting golgin (GORAB)
• Synonyms: N-terminal kinase-like-binding protein 1; NTKL-BP1; NTKL-binding protein 1; hNTKL-BP1; SCY1-like 1-binding protein 1; SCYL1-BP1; SCYL1-binding protein 1
• Gene Name: GORAB
• Related Disease:
  Diabetic retinopathy
  Geroderma osteodysplastica
  Non-insulin dependent diabetes
  Bone disease
  Hepatocellular carcinoma
  Neoplasm
  Osteoporosis
  Androgenetic alopecia
  Baldness, male pattern
• UniProt ID: GORAB_HUMAN
• Pfam ID: PF04949
• Sequence:
  MAQGWAGFSEEELRRLKQTKDPFEPQRRLPAKKSRQQLQREKALVEQSQKLGLQDGSTSL
  LPEQLLSAPKQRVNVQKPPFSSPTLPSHFTLTSPVGDGQPQGIESQPKELGLENSHDGHN
  NVEILPPKPDCKLEKKKVELQEKSRWEVLQQEQRLMEEKNKRKKALLAKAIAERSKRTQA
  ETMKLKRIQKELQALDDMVSADIGILRNRIDQASLDYSYARKRFDRAEAEYIAAKLDIQR
  KTEIKEQLTEHLCTIIQQNELRKAKKLEELMQQLDVEADEETLELEVEVERLLHEQEVES
  RRPVVRLERPFQPAEESVTLEFAKENRKCQEQAVSPKVDDQCGNSSSIPFLSPNCPNQEG
  NDISAALAT
• KEGG Pathway: p53 sig.ling pathway (hsa04115)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
Geroderma osteodysplastica	DISFPJ78	Definitive	Autosomal recessive	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Bone disease	DISE1F82	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[5]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[6]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RAB6-interacting golgin (GORAB).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RAB6-interacting golgin (GORAB).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RAB6-interacting golgin (GORAB).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RAB6-interacting golgin (GORAB).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of RAB6-interacting golgin (GORAB).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RAB6-interacting golgin (GORAB).	[12]

References

• [1] Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes.Diabetologia. 2015 Jun;58(6):1231-8. doi: 10.1007/s00125-015-3569-9. Epub 2015 Mar 28.
• [2] Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin. Nat Genet. 2008 Dec;40(12):1410-2. doi: 10.1038/ng.252. Epub 2008 Nov 9.
• [3] GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation.Nat Commun. 2019 Jan 10;10(1):127. doi: 10.1038/s41467-018-08044-6.
• [4] SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor-suppressive function in the development of hepatocellular carcinoma.Carcinogenesis. 2012 Aug;33(8):1581-8. doi: 10.1093/carcin/bgs162. Epub 2012 May 7.
• [5] Examining tissue composition, whole-bone morphology and mechanical behavior of Gorab(Prx1) mice tibiae: A mouse model of premature aging.J Biomech. 2017 Dec 8;65:145-153. doi: 10.1016/j.jbiomech.2017.10.018. Epub 2017 Oct 25.
• [6] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.