Details of Drug Off-Target (DOT)

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

• DOT Name: Tryptase gamma (TPSG1)
• Synonyms: EC 3.4.21.-; Serine protease 31; Transmembrane tryptase
• Gene Name: TPSG1
• Related Disease:
  Cognitive impairment
  Obsessive compulsive disorder
  Osteochondritis dissecans
  Parkinson disease
  Schizophrenia
  Type-1/2 diabetes
  Alzheimer disease
  Amyloidosis
  Attention deficit hyperactivity disorder
  Behavioral variant of frontotemporal dementia
  Bipolar disorder
  Brain cancer
  Brain neoplasm
  Breast carcinoma
  Breast neoplasm
  Cerebrovascular disease
  Chronic obstructive pulmonary disease
  Colitis
  Dementia
  Linear nevus sebaceous syndrome
  Frontal lobe epilepsy
  Anxiety disorder
  Depression
  Lewy body dementia
• UniProt ID: TRYG1_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MALGACGLLLLLAVPGVSLRTLQPGCGRPQVSDAGGRIVGGHAAPAGAWPWQASLRLRRV
  HVCGGSLLSPQWVLTAAHCFSGSLNSSDYQVHLGELEITLSPHFSTVRQIILHSSPSGQP
  GTSGDIALVELSVPVTLSSRILPVCLPEASDDFCPGIRCWVTGWGYTREGEPLPPPYSLR
  EVKVSVVDTETCRRDYPGPGGSILQPDMLCARGPGDACQDDSGGPLVCQVNGAWVQAGTV
  SWGEGCGRPNRPGVYTRVPAYVNWIRRHITASGGSESGYPRLPLLAGFFLPGLFLLLVSC
  VLLAKCLLHPSADGTPFPAPD
• Tissue Specificity: Expressed in many tissues.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[1]
Obsessive compulsive disorder	DIS1ZMM2	Definitive	Genetic Variation	[2]
Osteochondritis dissecans	DIS1FGN4	Definitive	Genetic Variation	[2]
Parkinson disease	DISQVHKL	Definitive	Genetic Variation	[3]
Schizophrenia	DISSRV2N	Definitive	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[5]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[6]
Behavioral variant of frontotemporal dementia	DISQHX2V	Strong	Biomarker	[7]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[8]
Brain cancer	DISBKFB7	Strong	Genetic Variation	[9]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[11]
Cerebrovascular disease	DISAB237	Strong	Biomarker	[12]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[13]
Colitis	DISAF7DD	Strong	Biomarker	[13]
Dementia	DISXL1WY	Strong	Biomarker	[14]
Linear nevus sebaceous syndrome	DIS6VQ2J	Strong	Biomarker	[10]
Frontal lobe epilepsy	DISHN8AO	moderate	Biomarker	[15]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[16]
Depression	DIS3XJ69	Limited	Biomarker	[17]
Lewy body dementia	DISAE66J	Limited	Biomarker	[18]

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 Tryptase gamma (TPSG1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tryptase gamma (TPSG1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tryptase gamma (TPSG1).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tryptase gamma (TPSG1).	[21]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tryptase gamma (TPSG1).	[22]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Tryptase gamma (TPSG1).	[23]

References

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• [2] Comparison of neurocognitive domains in patients with schizophrenia with and without co-morbid obsessive compulsive disorder.Schizophr Res. 2018 Nov;201:151-158. doi: 10.1016/j.schres.2018.05.029. Epub 2018 May 29.
• [3] Effects of Transcranial Direct Current Stimulation (tDCS) Over the Frontal Polar Area on Motor and Executive Functions in Parkinson's Disease; A Pilot Study.Front Aging Neurosci. 2018 Jul 30;10:231. doi: 10.3389/fnagi.2018.00231. eCollection 2018.
• [4] Effect of Chlorogenic Acids on Cognitive Function in Mild Cognitive Impairment: A Randomized Controlled Crossover Trial.J Alzheimers Dis. 2019;72(4):1209-1216. doi: 10.3233/JAD-190757.
• [5] Amyloid-, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.Front Aging Neurosci. 2018 Jun 25;10:193. doi: 10.3389/fnagi.2018.00193. eCollection 2018.
• [6] Executive Function Training for Children with Attention Deficit Hyperactivity Disorder.Chin Med J (Engl). 2017 Mar 5;130(5):549-558. doi: 10.4103/0366-6999.200541.
• [7] Reduced tendency to attribute mental states to abstract shapes in behavioral variant frontotemporal dementia links with cerebellar structural integrity.Neuroimage Clin. 2019;22:101770. doi: 10.1016/j.nicl.2019.101770. Epub 2019 Mar 12.
• [8] Tryptophan breakdown and cognition in bipolar disorder.Psychoneuroendocrinology. 2017 Jul;81:144-150. doi: 10.1016/j.psyneuen.2017.04.015. Epub 2017 Apr 27.
• [9] Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial.Lancet Oncol. 2019 Oct;20(10):1444-1453. doi: 10.1016/S1470-2045(19)30502-9. Epub 2019 Sep 2.
• [10] Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF-I and EGF.Int J Cancer. 2002 Jul 1;100(1):2-8. doi: 10.1002/ijc.10481.
• [11] Deep Coverage of Global Protein Expression and Phosphorylation in Breast Tumor Cell Lines Using TMT 10-plex Isobaric Labeling.J Proteome Res. 2017 Mar 3;16(3):1121-1132. doi: 10.1021/acs.jproteome.6b00374. Epub 2017 Feb 3.
• [12] Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests.Front Aging Neurosci. 2018 Jul 16;10:217. doi: 10.3389/fnagi.2018.00217. eCollection 2018.
• [13] Importance of mast cell Prss31/transmembrane tryptase/tryptase- in lung function and experimental chronic obstructive pulmonary disease and colitis.J Biol Chem. 2014 Jun 27;289(26):18214-27. doi: 10.1074/jbc.M114.548594. Epub 2014 May 12.
• [14] Errors versus speed on the trail making test: Relevance to driving performance.Accid Anal Prev. 2018 Apr;113:125-130. doi: 10.1016/j.aap.2018.01.004. Epub 2018 Mar 7.
• [15] Emotional asymmetries in refractory medial temporal and frontal lobe epilepsy: Their impact on predicting lateralization and localization of seizures.Epilepsy Behav. 2019 May;94:269-276. doi: 10.1016/j.yebeh.2019.03.008. Epub 2019 Apr 11.
• [16] Comparison of Neurological and Cognitive Deficits in Children With ADHD and Anxiety Disorders.J Atten Disord. 2018 Mar;22(5):472-485. doi: 10.1177/1087054715578003. Epub 2015 Jun 15.
• [17] Effects of MitraClip on cognitive and psychological function in heart failure patients: the sicker the better.Eur J Med Res. 2019 Feb 22;24(1):14. doi: 10.1186/s40001-019-0371-z.
• [18] A Longitudinal Study of Neurocognition in Dementia with Lewy Bodies Compared to Alzheimer's Disease.Front Neurol. 2018 Mar 6;9:124. doi: 10.3389/fneur.2018.00124. eCollection 2018.
• [19] 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.
• [20] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [21] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [22] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [23] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [24] 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.