Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4J7EFT)

• DOT Name: Trichohyalin (TCHH)
• Gene Name: TCHH
• Related Disease:
  B-cell neoplasm
  Atopic dermatitis
  Hydrocephalus
  Neoplasm
  Polycythemia
  Skin disease
  Skin neoplasm
  Uncombable hair syndrome
  Lymphoma
• UniProt ID: TRHY_HUMAN
• Pfam ID: PF01023
• Sequence:
  MSPLLRSICDITEIFNQYVSHDCDGAALTKKDLKNLLEREFGAVLRRPHDPKTVDLILEL
  LDLDSNGRVDFNEFLLFIFKVAQACYYALGQATGLDEEKRARCDGKESLLQDRRQEEDQR
  RFEPRDRQLEEEPGQRRRQKRQEQERELAEGEEQSEKQERLEQRDRQRRDEELWRQRQEW
  QEREERRAEEEQLQSCKGHETEEFPDEEQLRRRELLELRRKGREEKQQQRRERQDRVFQE
  EEEKEWRKRETVLRKEEEKLQEEEPQRQRELQEEEEQLRKLERQELRRERQEEEQQQQRL
  RREQQLRRKQEEERREQQEERREQQERREQQEERREQQLRREQEERREQQLRREQEEERR
  EQQLRREQEEERREQQLRREQQLRREQQLRREQQLRREQQLRREQQLRREQQLRREQQLR
  REQQLRREQEEERHEQKHEQERREQRLKREQEERRDWLKREEETERHEQERRKQQLKRDQ
  EEERRERWLKLEEEERREQQERREQQLRREQEERREQRLKRQEEEERLQQRLRSEQQLRR
  EQEERREQLLKREEEKRLEQERREQRLKREQEERRDQLLKREEERRQQRLKREQEERLEQ
  RLKREEVERLEQEERREQRLKREEPEEERRQQLLKSEEQEERRQQQLRREQQERREQRLK
  REEEEERLEQRLKREHEEERREQELAEEEQEQARERIKSRIPKWQWQLESEADARQSKVY
  SRPRKQEGQRRRQEQEEKRRRRESELQWQEEERAHRQQQEEEQRRDFTWQWQAEEKSERG
  RQRLSARPPLREQRERQLRAEERQQREQRFLPEEEEKEQRRRQRREREKELQFLEEEEQL
  QRRERAQQLQEEEDGLQEDQERRRSQEQRRDQKWRWQLEEERKRRRHTLYAKPALQEQLR
  KEQQLLQEEEEELQREEREKRRRQEQERQYREEEQLQQEEEQLLREEREKRRRQERERQY
  RKDKKLQQKEEQLLGEEPEKRRRQEREKKYREEEELQQEEEQLLREEREKRRRQEWERQY
  RKKDELQQEEEQLLREEREKRRLQERERQYREEEELQQEEEQLLGEERETRRRQELERQY
  RKEEELQQEEEQLLREEPEKRRRQERERQCREEEELQQEEEQLLREEREKRRRQELERQY
  REEEEVQQEEEQLLREEPEKRRRQELERQYREEEELQQEEEQLLREEQEKRRQERERQYR
  EEEELQRQKRKQRYRDEDQRSDLKWQWEPEKENAVRDNKVYCKGRENEQFRQLEDSQLRD
  RQSQQDLQHLLGEQQERDREQERRRWQQRDRHFPEEEQLEREEQKEAKRRDRKSQEEKQL
  LREEREEKRRRQETDRKFREEEQLLQEREEQPLRRQERDRKFREEELRHQEQGRKFLEEE
  QRLRRQERERKFLKEEQQLRCQEREQQLRQDRDRKFREEEQQLSRQERDRKFREEEQQVR
  RQERERKFLEEEQQLRQERHRKFREEEQLLQEREEQQLHRQERDRKFLEEEQQLRRQERD
  RKFREQELRSQEPERKFLEEEQQLHRQQRQRKFLQEEQQLRRQERGQQRRQDRDRKFREE
  EQLRQEREEQQLSRQERDRKFRLEEQKVRRQEQERKFMEDEQQLRRQEGQQQLRQERDRK
  FREDEQLLQEREEQQLHRQERDRKFLEEEPQLRRQEREQQLRHDRDRKFREEEQLLQEGE
  EQQLRRQERDRKFREEEQQLRRQERERKFLQEEQQLRRQELERKFREEEQLRQETEQEQL
  RRQERYRKILEEEQLRPEREEQQLRRQERDRKFREEEQLRQEREEQQLRSQESDRKFREE
  EQLRQEREEQQLRPQQRDGKYRWEEEQLQLEEQEQRLRQERDRQYRAEEQFATQEKSRRE
  EQELWQEEEQKRRQERERKLREEHIRRQQKEEQRHRQVGEIKSQEGKGHGRLLEPGTHQF
  ASVPVRSSPLYEYIQEQRSQYRP
• Function: Intermediate filament-associated protein that associates in regular arrays with keratin intermediate filaments (KIF) of the inner root sheath cells of the hair follicle and the granular layer of the epidermis. It later becomes cross-linked to KIF by isodipeptide bonds. It may serve as scaffold protein, together with involucrin, in the organization of the cell envelope or even anchor the cell envelope to the KIF network. It may be involved in its own calcium-dependent postsynthetic processing during terminal differentiation.
• Tissue Specificity: Found in the hard keratinizing tissues such as the inner root sheath (IRS) of hair follicles and medulla, and in the filiform papillae of dorsal tongue epithelium.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[2]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Polycythemia	DIS8B6VW	Strong	Biomarker	[5]
Skin disease	DISDW8R6	Strong	Biomarker	[6]
Skin neoplasm	DIS16DDV	Strong	Biomarker	[7]
Uncombable hair syndrome	DISJNMLZ	Strong	Genetic Variation	[8]
Lymphoma	DISN6V4S	moderate	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Trichohyalin (TCHH).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Trichohyalin (TCHH).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Trichohyalin (TCHH).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Trichohyalin (TCHH).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Trichohyalin (TCHH).	[14]

References

• [1] Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review.Int J Clin Exp Pathol. 2013;6(4):788-94. Epub 2013 Mar 15.
• [2] A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis.Hum Mol Genet. 2013 Dec 1;22(23):4841-56. doi: 10.1093/hmg/ddt317. Epub 2013 Jul 25.
• [3] Endoscopic ventriculo-cisterno-ventricular approach in the treatment of bilateral trapped temporal horn related to fungal infection in a child: case report and review of the literature.Childs Nerv Syst. 2018 Aug;34(8):1593-1597. doi: 10.1007/s00381-018-3776-z. Epub 2018 Mar 20.
• [4] Advances in pathological understanding of high-grade B cell lymphomas.Expert Rev Hematol. 2018 Aug;11(8):637-648. doi: 10.1080/17474086.2018.1494567. Epub 2018 Jul 10.
• [5] Experimental Study on the Effect of Tibetan Medicine Triphala on the Proliferation and Apoptosis of Pancreatic Islet Cells through Incretin-cAMP Signaling Pathway.Biol Pharm Bull. 2020 Feb 1;43(2):289-295. doi: 10.1248/bpb.b19-00562. Epub 2019 Dec 6.
• [6] Expression of keratohyalin-trichohyalin hybrid granules in molluscum contagiosum.Int J Dermatol. 1996 Feb;35(2):106-8. doi: 10.1111/j.1365-4362.1996.tb03271.x.
• [7] Trichohyalin expression in skin tumors: retrieval of trichohyalin antigenicity in tissues by microwave irradiation.Int J Dermatol. 1996 May;35(5):325-9. doi: 10.1111/j.1365-4362.1996.tb03632.x.
• [8] Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome. Am J Hum Genet. 2016 Dec 1;99(6):1292-1304. doi: 10.1016/j.ajhg.2016.10.004. Epub 2016 Nov 17.
• [9] Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for double hit and triple hit B-cell lymphomas.Leuk Res. 2015 Jul;39(7):730-8. doi: 10.1016/j.leukres.2015.04.003. Epub 2015 Apr 17.
• [10] 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.
• [11] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [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] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.