Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4WA5YQ)

• DOT Name: Histidine decarboxylase (HDC)
• Synonyms: HDC; EC 4.1.1.22
• Gene Name: HDC
• Related Disease: Tourette syndrome
• UniProt ID: DCHS_HUMAN
• PDB ID: 4E1O; 7EIW; 7EIX; 7EIY
• EC Number: 4.1.1.22
• Pfam ID: PF00282
• Sequence:
  MMEPEEYRERGREMVDYICQYLSTVRERRVTPDVQPGYLRAQLPESAPEDPDSWDSIFGD
  IERIIMPGVVHWQSPHMHAYYPALTSWPSLLGDMLADAINCLGFTWASSPACTELEMNVM
  DWLAKMLGLPEHFLHHHPSSQGGGVLQSTVSESTLIALLAARKNKILEMKTSEPDADESC
  LNARLVAYASDQAHSSVEKAGLISLVKMKFLPVDDNFSLRGEALQKAIEEDKQRGLVPVF
  VCATLGTTGVCAFDCLSELGPICAREGLWLHIDAAYAGTAFLCPEFRGFLKGIEYADSFT
  FNPSKWMMVHFDCTGFWVKDKYKLQQTFSVNPIYLRHANSGVATDFMHWQIPLSRRFRSV
  KLWFVIRSFGVKNLQAHVRHGTEMAKYFESLVRNDPSFEIPAKRHLGLVVFRLKGPNCLT
  ENVLKEIAKAGRLFLIPATIQDKLIIRFTVTSQFTTRDDILRDWNLIRDAATLILSQHCT
  SQPSPRVGNLISQIRGARAWACGTSLQSVSGAGDDPVQARKIIKQPQRVGAGPMKRENGL
  HLETLLDPVDDCFSEEAPDATKHKLSSFLFSYLSVQTKKKTVRSLSCNSVPVSAQKPLPT
  EASVKNGGSSRVRIFSRFPEDMMMLKKSAFKKLIKFYSVPSFPECSSQCGLQLPCCPLQA
  MV
• Function: Catalyzes the biosynthesis of histamine from histidine.
• KEGG Pathway:
  Histidine metabolism (hsa00340)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Histidine catabolism (R-HSA-70921)
• BioCyc Pathway: MetaCyc:HS06697-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Histidine decarboxylase (HDC).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Histidine decarboxylase (HDC).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histidine decarboxylase (HDC).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histidine decarboxylase (HDC).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Histidine decarboxylase (HDC).	[5]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Histidine decarboxylase (HDC).	[6]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Histidine decarboxylase (HDC).	[8]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Histidine decarboxylase (HDC).	[8]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the activity of Histidine decarboxylase (HDC).	[9]

6 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion affects the binding of Histidine decarboxylase (HDC).	[7]
Isoflurophate	DMBSK7X	Approved	Isoflurophate affects the binding of Histidine decarboxylase (HDC).	[7]
Glyphosate	DM0AFY7	Investigative	Glyphosate affects the binding of Histidine decarboxylase (HDC).	[7]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos affects the binding of Histidine decarboxylase (HDC).	[7]
Paraoxon	DMN4ZKC	Investigative	Paraoxon affects the binding of Histidine decarboxylase (HDC).	[7]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon affects the binding of Histidine decarboxylase (HDC).	[7]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] 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.
• [3] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [4] Inhibitory effect of quercetin on tryptase and MCP-1 chemokine release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. Neuroimmunomodulation. 2006;13(3):179-86. doi: 10.1159/000098131. Epub 2006 Dec 21.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma. Eur J Pharmacol. 2002 Feb 1;436(1-2):7-13. doi: 10.1016/s0014-2999(01)01577-1.
• [7] Decarboxylases as hypothetical targets for actions of organophosphates: Molecular modeling for prediction of hidden and unexpected health threats. Food Chem Toxicol. 2022 Mar;161:112856. doi: 10.1016/j.fct.2022.112856. Epub 2022 Feb 11.
• [8] The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. Blood. 2006 Nov 15;108(10):3538-47. doi: 10.1182/blood-2005-12-028456. Epub 2006 Jul 18.
• [9] Modulation of histidine decarboxylase activity and cytokine synthesis in human leukemic cell lines: relationship with basophilic and/or megakaryocytic differentiation. Exp Hematol. 1999 Aug;27(8):1295-305. doi: 10.1016/s0301-472x(99)00070-3.
• [10] 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.