Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM2V2R0)

• DOT Name: Ras-related protein Rab-40C (RAB40C)
• Synonyms: Rar-like protein; Ras-like protein family member 8C; SOCS box-containing protein RAR3
• Gene Name: RAB40C
• Related Disease:
  Duchenne muscular dystrophy
  Gastric cancer
  Stomach cancer
• UniProt ID: RB40C_HUMAN
• Pfam ID: PF00071 ; PF07525
• Sequence:
  MGSQGSPVKSYDYLLKFLLVGDSDVGKGEILESLQDGAAESPYAYSNGIDYKTTTILLDG
  RRVKLELWDTSGQGRFCTIFRSYSRGAQGILLVYDITNRWSFDGIDRWIKEIDEHAPGVP
  RILVGNRLHLAFKRQVPTEQARAYAEKNCMTFFEVSPLCNFNVIESFTELSRIVLMRHGM
  EKIWRPNRVFSLQDLCCRAIVSCTPVHLIDKLPLPVTIKSHLKSFSMANGMNAVMMHGRS
  YSLASGAGGGGSKGNSLKRSKSIRPPQSPPQNCSRSNCKIS
• Function: Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Duchenne muscular dystrophy	DISRQ3NV	Strong	Genetic Variation	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras-related protein Rab-40C (RAB40C).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rab-40C (RAB40C).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras-related protein Rab-40C (RAB40C).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-related protein Rab-40C (RAB40C).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ras-related protein Rab-40C (RAB40C).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ras-related protein Rab-40C (RAB40C).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related protein Rab-40C (RAB40C).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras-related protein Rab-40C (RAB40C).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ras-related protein Rab-40C (RAB40C).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ras-related protein Rab-40C (RAB40C).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ras-related protein Rab-40C (RAB40C).	[12]

References

• [1] The Xq22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation.Am J Hum Genet. 2002 Sep;71(3):637-45. doi: 10.1086/342208. Epub 2002 Jul 23.
• [2] Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C.Carcinogenesis. 2011 May;32(5):713-22. doi: 10.1093/carcin/bgr035. Epub 2011 Feb 24.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro: estrogen receptor dependent or independent pathways of raloxifene. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):281-9.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] 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.
• [13] Identification of formaldehyde-responsive genes by suppression subtractive hybridization. Toxicology. 2008 Jan 14;243(1-2):224-35.