Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB5NV8A)

• DOT Name: Golgi integral membrane protein 4 (GOLIM4)
• Synonyms: Golgi integral membrane protein, cis; GIMPc; Golgi phosphoprotein 4; Golgi-localized phosphoprotein of 130 kDa; Golgi phosphoprotein of 130 kDa
• Gene Name: GOLIM4
• Related Disease:
  Alzheimer disease
  Head and neck cancer
  Head and neck carcinoma
  Neoplasm
  Nasopharyngeal carcinoma
• UniProt ID: GOLI4_HUMAN
• Sequence:
  MGNGMCSRKQKRIFQTLLLLTVVFGFLYGAMLYYELQTQLRKAEAVALKYQQHQESLSAQ
  LQVVYEHRSRLEKSLQKERLEHKKAKEDFLVYKLEAQETLNKGRQDSNSRYSALNVQHQM
  LKSQHEELKKQHSDLEEEHRKQGEDFSRTFNDHKQKYLQLQQEKEQELSKLKETVYNLRE
  ENRQLRKAHQDIHTQLQDVKQQHKNLLSEHEQLVVTLEDHKSALAAAQTQVAEYKQLKDT
  LNRIPSLRKPDPAEQQNVTQVAHSPQGYNTAREKPTREVQEVSRNNDVWQNHEAVPGRAE
  DTKLYAPTHKEAEFQAPPEPIQQEVERREPEEHQVEEEHRKALEEEEMEQVGQAEHLEEE
  HDPSPEEQDREWKEQHEQREAANLLEGHARAEVYPSAKPMIKFQSPYEEQLEQQRLAVQQ
  VEEAQQLREHQEALHQQRLQGHLLRQQEQQQQQVAREMALQRQAELEEGRPQHQEQLRQQ
  AHYDAMDNDIVQGAEDQGIQGEEGAYERDNQHQDEAEGDPGNRHEPREQGPREADPESEA
  DRAAVEDINPADDPNNQGEDEFEEAEQVREENLPDENEEQKQSNQKQENTEVEEHLVMAG
  NPDQQEDNVDEQYQEEAEEEVQEDLTEEKKRELEHNAEETYGENDENTDDKNNDGEEQEV
  RDDNRPKGREEHYEEEEEEEEDGAAVAEKSHRRAEM
• Function: Plays a role in endosome to Golgi protein trafficking; mediates protein transport along the late endosome-bypass pathway from the early endosome to the Golgi.
• Reactome Pathway: Intra-Golgi traffic (R-HSA-6811438)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[2]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Golgi integral membrane protein 4 (GOLIM4) increases the Metabolic disorder ADR of Chlorothiazide.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Golgi integral membrane protein 4 (GOLIM4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Golgi integral membrane protein 4 (GOLIM4).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Golgi integral membrane protein 4 (GOLIM4).	[11]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[8]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Golgi integral membrane protein 4 (GOLIM4).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Golgi integral membrane protein 4 (GOLIM4).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[13]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Golgi integral membrane protein 4 (GOLIM4).	[14]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Golgi integral membrane protein 4 (GOLIM4).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Golgi integral membrane protein 4 (GOLIM4).	[16]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Golgi integral membrane protein 4 (GOLIM4).	[17]

References

• [1] Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.Alzheimers Dement. 2018 May;14(5):623-633. doi: 10.1016/j.jalz.2017.11.006. Epub 2017 Dec 20.
• [2] Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer.Biosci Rep. 2018 Aug 31;38(4):BSR20180454. doi: 10.1042/BSR20180454. Print 2018 Aug 31.
• [3] Native early antigen of Epstein-Barr virus, a promising antigen for diagnosis of nasopharyngeal carcinoma.J Med Virol. 2007 Nov;79(11):1710-21. doi: 10.1002/jmv.20987.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [12] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [13] 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.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [18] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.