Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVM43E3)

• DOT Name: Gasdermin-C (GSDMC)
• Synonyms: Melanoma-derived leucine zipper-containing extranuclear factor
• Gene Name: GSDMC
• Related Disease:
  Glioma
  Colorectal carcinoma
  Gastric cancer
  Neoplasm
• UniProt ID: GSDMC_HUMAN
• Pfam ID: PF04598 ; PF17708
• Sequence:
  MPSMLERISKNLVKEIGSKDLTPVKYLLSATKLRQFVILRKKKDSRSSFWEQSDYVPVEF
  SLNDILEPSSSVLETVVTGPFHFSDIMIQKHKADMGVNVGIEVSVSGEASVDHGCSLEFQ
  IVTIPSPNLEDFQKRKLLDPEPSFLKECRRRGDNLYVVTEAVELINNTVLYDSSSVNILG
  KIALWITYGKGQGQGESLRVKKKALTLQKGMVMAYKRKQLVIKEKAILISDDDEQRTFQD
  EYEISEMVGYCAARSEGLLPSFHTISPTLFNASSNDMKLKPELFLTQQFLSGHLPKYEQV
  HILPVGRIEEPFWQNFKHLQEEVFQKIKTLAQLSKDVQDVMFYSILAMLRDRGALQDLMN
  MLELDSSGHLDGPGGAILKKLQQDSNHAWFNPKDPILYLLEAIMVLSDFQHDLLACSMEK
  RILLQQQELVRSILEPNFRYPWSIPFTLKPELLAPLQSEGLAITYGLLEECGLRMELDNP
  RSTWDVEAKMPLSALYGTLSLLQQLAEA
• Function: [Gasdermin-C]: This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C, N-terminal) binds to membranes and forms pores, triggering pyroptosis; [Gasdermin-C, N-terminal]: Pore-forming protein that causes membrane permeabilization and pyroptosis. Produced by the cleavage of gasdermin-D by caspase CASP8 in response to death signals. After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis.
• Tissue Specificity: Expressed mainly in trachea and spleen . In the esophagus, expressed in differentiating cells and probably in differentiated cells. Also detected in gastric epithelium .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]

1 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 decreases the methylation of Gasdermin-C (GSDMC).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Gasdermin-C (GSDMC).	[5]

References

• [1] Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.Am J Epidemiol. 2011 Sep 1;174(5):574-81. doi: 10.1093/aje/kwr124. Epub 2011 Jul 8.
• [2] Gasdermin C Is Upregulated by Inactivation of Transforming Growth Factor Receptor Type II in the Presence of Mutated Apc, Promoting Colorectal Cancer Proliferation.PLoS One. 2016 Nov 11;11(11):e0166422. doi: 10.1371/journal.pone.0166422. eCollection 2016.
• [3] Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium.Genes Chromosomes Cancer. 2009 Mar;48(3):261-71. doi: 10.1002/gcc.20636.
• [4] 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.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.