Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNQ040R)

• DOT Name: Keratin, type II cuticular Hb3 (KRT83)
• Synonyms: Hair keratin K2.10; Keratin-83; K83; Type II hair keratin Hb3; Type-II keratin Kb23
• Gene Name: KRT83
• Related Disease:
  Monilethrix
  Acute myelogenous leukaemia
  Erythrokeratodermia variabilis
• UniProt ID: KRT83_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MTCGFNSIGCGFRPGNFSCVSACGPRPSRCCITAAPYRGISCYRGLTGGFGSHSVCGGFR
  AGSCGRSFGYRSGGVCGPSPPCITTVSVNESLLTPLNLEIDPNAQCVKQEEKEQIKSLNS
  RFAAFIDKVRFLEQQNKLLETKLQFYQNRECCQSNLEPLFAGYIETLRREAECVEADSGR
  LASELNHVQEVLEGYKKKYEEEVALRATAENEFVALKKDVDCAYLRKSDLEANVEALIQE
  IDFLRRLYEEEIRILQSHISDTSVVVKLDNSRDLNMDCIVAEIKAQYDDIATRSRAEAES
  WYRSKCEEMKATVIRHGETLRRTKEEINELNRMIQRLTAEVENAKCQNSKLEAAVAQSEQ
  QGEAALSDARCKLAELEGALQKAKQDMACLIREYQEVMNSKLGLDIEIATYRRLLEGEEQ
  RLCEGVEAVNVCVSSSRGGVVCGDLCVSGSRPVTGSVCSAPCNGNLVVSTGLCKPCGQLN
  TTCGGGSCGQGRH
• Tissue Specificity: Synthesis begins in the cortex 10-15 cell layers above the apex of the dermal papilla and ends abruptly in the middle of the cortex.
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Monilethrix	DISF9MNT	Strong	Autosomal dominant	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Erythrokeratodermia variabilis	DIS4BMUQ	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Keratin, type II cuticular Hb3 (KRT83).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Keratin, type II cuticular Hb3 (KRT83).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Keratin, type II cuticular Hb3 (KRT83).	[6]

References

• [1] A missense mutation in the type II hair keratin hHb3 is associated with monilethrix. J Med Genet. 2005 Mar;42(3):e19. doi: 10.1136/jmg.2004.021030.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Recessive progressive symmetric erythrokeratoderma results from a homozygous loss-of-function mutation of KRT83 and is allelic with dominant monilethrix. J Med Genet. 2017 Mar;54(3):186-189. doi: 10.1136/jmedgenet-2016-104107. Epub 2016 Dec 13.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [6] 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.