Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB6RCAH)

• DOT Name: Keratin, type I cuticular Ha1 (KRT31)
• Synonyms: Hair keratin, type I Ha1; Keratin-31; K31
• Gene Name: KRT31
• Related Disease:
  Advanced cancer
  Hydatidiform mole
  Hydatidiform mole, recurrent, 1
  Influenza
  Neoplasm
  Obesity
  Small lymphocytic lymphoma
  Factor IX deficiency
  Acute myelogenous leukaemia
  Myeloid leukaemia
  Non-insulin dependent diabetes
  Parkinson disease
• UniProt ID: K1H1_HUMAN
• Pfam ID: PF00038
• Sequence:
  MPYNFCLPSLSCRTSCSSRPCVPPSCHSCTLPGACNIPANVSNCNWFCEGSFNGSEKETM
  QFLNDRLASYLEKVRQLERDNAELENLIRERSQQQEPLLCPSYQSYFKTIEELQQKILCT
  KSENARLVVQIDNAKLAADDFRTKYQTELSLRQLVESDINGLRRILDELTLCKSDLEAQV
  ESLKEELLCLKSNHEQEVNTLRCQLGDRLNVEVDAAPTVDLNRVLNETRSQYEALVETNR
  REVEQWFTTQTEELNKQVVSSSEQLQSYQAEIIELRRTVNALEIELQAQHNLRDSLENTL
  TESEARYSSQLSQVQSLITNVESQLAEIRSDLERQNQEYQVLLDVRARLECEINTYRSLL
  ESEDCNLPSNPCATTNACSKPIGPCLSNPCTSCVPPAPCTPCAPRPRCGPCNSFVR
• Tissue Specificity: Present in scalp but not in hairless skin. Abundantly expressed in the differentiating cortex of growing (anagen) hair. Expression is restricted to the keratinocytes of the hair cortex and is absent from inner root sheath and medulla.
• KEGG Pathway:
  Estrogen sig.ling pathway (hsa04915)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hydatidiform mole	DISKNP7O	Strong	Biomarker	[2]
Hydatidiform mole, recurrent, 1	DISXUJWE	Strong	Biomarker	[2]
Influenza	DIS3PNU3	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[4]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[5]
Factor IX deficiency	DISHN9SC	moderate	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[7]
Myeloid leukaemia	DISMN944	Limited	Posttranslational Modification	[7]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[8]
Parkinson disease	DISQVHKL	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Keratin, type I cuticular Ha1 (KRT31).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Keratin, type I cuticular Ha1 (KRT31).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Keratin, type I cuticular Ha1 (KRT31).	[13]

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 increases the methylation of Keratin, type I cuticular Ha1 (KRT31).	[11]

References

• [1] Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy. Blood. 2009 Mar 19;113(12):2715-22. doi: 10.1182/blood-2008-05-158956. Epub 2008 Dec 18.
• [2] Relative levels of methylation in human growth hormone and chorionic somatomammotropin genes in expressing and non-expressing tissues.Nucleic Acids Res. 1982 Jun 11;10(11):3459-74. doi: 10.1093/nar/10.11.3459.
• [3] Structure of general-population antibody titer distributions to influenza A virus.Sci Rep. 2017 Jul 20;7(1):6060. doi: 10.1038/s41598-017-06177-0.
• [4] Analysis of MC4R rs17782313, POMC rs1042571, APOE-Hha1 and AGRP rs3412352 genetic variants with susceptibility to obesity risk in North Indians.Ann Hum Biol. 2016 May;43(3):285-8. doi: 10.3109/03014460.2015.1061597. Epub 2015 Jul 31.
• [5] 1513A/C polymorphism in the P2X7 receptor gene in chronic lymphocytic leukemia: absence of correlation with clinical outcome.Eur J Haematol. 2004 Apr;72(4):259-63. doi: 10.1111/j.0902-4441.2003.00210.x.
• [6] Diagnosis of hemophilia B carriers using two novel dinucleotide polymorphisms and Hha I RFLP of the factor IX gene in Japanese subjects.Thromb Haemost. 1995 Oct;74(4):1009-14.
• [7] Investigation of methylation at Hha I sites using the hypervariable probe M27 beta allows improved clonal analysis in myeloid leukaemia and demonstrates differences in methylation between leukaemic and remission samples.Leukemia. 1994 Jan;8(1):190-4.
• [8] Association of APOE (Hha1) and ACE (I/D) gene polymorphisms with type 2 diabetes mellitus in North West India.Diabetes Res Clin Pract. 2006 Oct;74(1):95-102. doi: 10.1016/j.diabres.2006.03.013. Epub 2006 Apr 18.
• [9] Lack of relation between genetic polymorphism of cytochrome P-450IID6 and sporadic idiopathic Parkinson's disease.Clin Neuropharmacol. 1996 Jun;19(3):213-21. doi: 10.1097/00002826-199619030-00003.
• [10] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.