Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJKA8C)

DOT Name	Granulysin (GNLY)
Synonyms	Lymphokine LAG-2; Protein NKG5; T-cell activation protein 519
Gene Name	GNLY
Related Disease	Acne vulgaris ( ) Adult lymphoma ( ) Anaplastic large cell lymphoma ( ) Pediatric lymphoma ( ) Type-1/2 diabetes ( ) Acute megakaryoblastic leukemia ( ) Acute myocardial infarction ( ) Advanced cancer ( ) Anemia ( ) Anxiety disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiac failure ( ) Congestive heart failure ( ) Cryptococcosis ( ) Cytomegalovirus infection ( ) Exanthem ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Latent tuberculosis infection ( ) Leukemia ( ) Lichen planus ( ) Myocardial infarction ( ) Neoplasm ( ) Plasmodium falciparum malaria ( ) Polymyositis ( ) Psoriasis ( ) Pulmonary tuberculosis ( ) Schwartz-Jampel syndrome ( ) Scrub typhus ( ) Stevens-Johnson syndrome ( ) Toxic epidermal necrolysis ( ) Tuberculosis ( ) Urinary tract infection ( ) Graft-versus-host disease ( ) Myocardial ischemia ( ) Plasma cell myeloma ( ) Small lymphocytic lymphoma ( ) T-cell lymphoma ( ) Familial hemophagocytic lymphohistiocytosis 2 ( ) Primary biliary cholangitis ( ) Extranodal NK/T-cell Lymphoma ( ) Lymphoma ( ) Metastatic malignant neoplasm ( ) T-cell acute lymphoblastic leukaemia ( )
UniProt ID	GNLY_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1L9L
Pfam ID	PF03489
Sequence	MATWALLLLAAMLLGNPGLVFSRLSPEYYDLARAHLRDEEKSCPCLAQEGPQGDLLTKTQ ELGRDYRTCLTIVQKLKKMVDKPTQRSVSNAATRVCRTGRSRWRDVCRNFMRRYQSRVTQ GLVAGETAQQICEDLRLCIPSTGPL
Function	Antimicrobial protein that kills intracellular pathogens. Active against a broad range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium tuberculosis.
Tissue Specificity	Expressed in natural killer and T-cells.
Reactome Pathway	Antimicrobial peptides (R-HSA-6803157 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acne vulgaris	DISKW8PI	Definitive	Biomarker	[1]
Adult lymphoma	DISK8IZR	Definitive	Biomarker	[2]
Anaplastic large cell lymphoma	DISP4D1R	Definitive	Biomarker	[3]
Pediatric lymphoma	DIS51BK2	Definitive	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[4]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Altered Expression	[5]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Anemia	DISTVL0C	Strong	Biomarker	[8]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cardiac failure	DISDC067	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[11]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[12]
Exanthem	DISAFOQN	Strong	Biomarker	[13]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Latent tuberculosis infection	DIS6R1EH	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Altered Expression	[5]
Lichen planus	DISRPMMS	Strong	Altered Expression	[17]
Myocardial infarction	DIS655KI	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Plasmodium falciparum malaria	DIS3Q9KF	Strong	Biomarker	[20]
Polymyositis	DIS5DHFP	Strong	Altered Expression	[21]
Psoriasis	DIS59VMN	Strong	Biomarker	[22]
Pulmonary tuberculosis	DIS6FLUM	Strong	Biomarker	[23]
Schwartz-Jampel syndrome	DIS3HCR8	Strong	Biomarker	[24]
Scrub typhus	DISRXONX	Strong	Biomarker	[25]
Stevens-Johnson syndrome	DISZG4YX	Strong	Genetic Variation	[24]
Toxic epidermal necrolysis	DISIWPFR	Strong	Biomarker	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[23]
Urinary tract infection	DISMT6UV	Strong	Biomarker	[26]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[27]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[28]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[7]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[29]
T-cell lymphoma	DISSXRTQ	moderate	Altered Expression	[7]
Familial hemophagocytic lymphohistiocytosis 2	DISBBSGH	Disputed	Biomarker	[30]
Primary biliary cholangitis	DIS43E0O	Disputed	Biomarker	[31]
Extranodal NK/T-cell Lymphoma	DIS72GCL	Limited	Biomarker	[7]
Lymphoma	DISN6V4S	Limited	Altered Expression	[7]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[32]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[33]
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⏷ Show the Full List of 45 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of Granulysin (GNLY).	[34]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Granulysin (GNLY).	[35]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Granulysin (GNLY).	[37]
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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 decreases the methylation of Granulysin (GNLY).	[36]
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References

1	Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against Propionibacterium acnes.J Invest Dermatol. 2005 Aug;125(2):256-63. doi: 10.1111/j.0022-202X.2005.23805.x.
2	Granulysin-mediated tumor rejection in transgenic mice.J Immunol. 2007 Jan 1;178(1):77-84. doi: 10.4049/jimmunol.178.1.77.
3	The expression of granulysin in systemic anaplastic large cell lymphoma in childhood.Leuk Res. 2009 Jul;33(7):908-12. doi: 10.1016/j.leukres.2009.01.032. Epub 2009 Feb 24.
4	Association between incidence of fatal intracerebral hemorrhagic stroke and fine particulate air pollution.Environ Health Prev Med. 2019 Jun 1;24(1):38. doi: 10.1186/s12199-019-0793-9.
5	Expression of granulysin mRNA in the human megakaryoblastic leukemia cell line CMK.Acta Haematol. 2002;108(1):13-8. doi: 10.1159/000063061.
6	Air Pollution and Hospitalization for Acute Myocardial Infarction in China.Am J Cardiol. 2017 Sep 1;120(5):753-758. doi: 10.1016/j.amjcard.2017.06.004. Epub 2017 Jun 15.
7	Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type.Virchows Arch. 2018 Dec;473(6):749-757. doi: 10.1007/s00428-018-2434-x. Epub 2018 Aug 27.
8	T cell and monocyte/macrophage activation markers associate with adverse outcome, but give limited prognostic value in anemic patients with heart failure: results from RED-HF.Clin Res Cardiol. 2019 Feb;108(2):133-141. doi: 10.1007/s00392-018-1331-2. Epub 2018 Jul 26.
9	Search trends preceding increases in suicide: A cross-correlation study of monthly Google search volume and suicide rate using transfer function models.J Affect Disord. 2020 Feb 1;262:155-164. doi: 10.1016/j.jad.2019.11.014. Epub 2019 Nov 4.
10	Anti-tumoral potential of a human granulysin-based, CEA-targeted cytolytic immunotoxin.Oncoimmunology. 2019 Jul 22;8(11):1641392. doi: 10.1080/2162402X.2019.1641392. eCollection 2019.
11	Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients.Blood. 2007 Mar 1;109(5):2049-57. doi: 10.1182/blood-2006-03-009720. Epub 2006 Oct 12.
12	Transcriptional profiles in urine during acute rejection, bacteriuria, CMV infection and stable graft function after renal transplantation.Scand J Immunol. 2009 Apr;69(4):357-65. doi: 10.1111/j.1365-3083.2009.02226.x.
13	Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients.J Am Acad Dermatol. 2017 Apr;76(4):722-729. doi: 10.1016/j.jaad.2016.10.022. Epub 2016 Dec 24.
14	Effects of interaction between genetic variants in human leukocyte antigen DQ and granulysin genes in Chinese Han subjects infected with hepatitis B virus.Microbiol Immunol. 2015 Apr;59(4):209-18. doi: 10.1111/1348-0421.12239.
15	Delta-like 3 is silenced by HBx via histone acetylation in HBV-associated HCCs.Sci Rep. 2018 Mar 19;8(1):4842. doi: 10.1038/s41598-018-23318-1.
16	Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.BMC Infect Dis. 2016 Oct 18;16(1):580. doi: 10.1186/s12879-016-1911-6.
17	Involvement of granzyme B and granulysin in the cytotoxic response in lichen planus.J Cutan Pathol. 2008 Jul;35(7):630-4. doi: 10.1111/j.1600-0560.2007.00892.x. Epub 2008 Mar 10.
18	Granulysin Expression in Lymphocytes that Populate the Peripheral Blood and the Myocardium after an Acute Coronary Event.Scand J Immunol. 2012 Feb;75(2):231-42. doi: 10.1111/j.1365-3083.2011.02646.x.
19	Granulysin: The attractive side of a natural born killer.Immunol Lett. 2020 Jan;217:126-132. doi: 10.1016/j.imlet.2019.11.005. Epub 2019 Nov 11.
20	Control of Plasmodium falciparum erythrocytic cycle: T cells target the red blood cell-invasive merozoites.Blood. 2011 Dec 22;118(26):6952-62. doi: 10.1182/blood-2011-08-376111. Epub 2011 Nov 1.
21	Expression of granulysin in polymyositis and inclusion-body myositis.J Neurol Neurosurg Psychiatry. 2006 Oct;77(10):1187-90. doi: 10.1136/jnnp.2005.081810.
22	Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis.Acta Derm Venereol. 2019 Nov 1;99(12):1136-1142. doi: 10.2340/00015555-3298.
23	1, 25-dihydroxyvitamin D(3) downregulates cytotoxic effector response in pulmonary tuberculosis.Int Immunopharmacol. 2018 Sep;62:251-260. doi: 10.1016/j.intimp.2018.07.018. Epub 2018 Jul 20.
24	Mutant GNLY is linked to Stevens-Johnson syndrome and toxic epidermal necrolysis.Hum Genet. 2019 Dec;138(11-12):1267-1274. doi: 10.1007/s00439-019-02066-w. Epub 2019 Oct 14.
25	A Case Report and Literature Review of Scrub Typhus With Acute Abdomen and Septic Shock in a Child-The Role of Leukocytoclastic Vasculitis and Granulysin.Am J Dermatopathol. 2018 Oct;40(10):767-771. doi: 10.1097/DAD.0000000000001167.
26	The selective biomarker IL-8 identifies IFTA after kidney transplantation in blood cells.Transpl Immunol. 2016 Nov;39:18-24. doi: 10.1016/j.trim.2016.09.003. Epub 2016 Sep 29.
27	A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders.J Allergy Clin Immunol. 2013 Sep;132(3):713-722.e11. doi: 10.1016/j.jaci.2013.04.036. Epub 2013 Jun 19.
28	Association between Airborne Fine Particulate Matter and Residents' Cardiovascular Diseases, Ischemic Heart Disease and Cerebral Vascular Disease Mortality in Areas with Lighter Air Pollution in China.Int J Environ Res Public Health. 2018 Sep 3;15(9):1918. doi: 10.3390/ijerph15091918.
29	Granulysin induces apoptotic cell death and cleavage of the autophagy regulator Atg5 in human hematological tumors.Biochem Pharmacol. 2014 Feb 1;87(3):410-23. doi: 10.1016/j.bcp.2013.11.004. Epub 2013 Nov 22.
30	HLH-2/E2A Expression Links Stochastic and Deterministic Elements of a Cell Fate Decision during C.elegans Gonadogenesis.Curr Biol. 2019 Sep 23;29(18):3094-3100.e4. doi: 10.1016/j.cub.2019.07.062. Epub 2019 Aug 8.
31	Increased granulysin expression in peripheral blood cells of patients with primary biliary cirrhosis and its clinical implications.J Clin Immunol. 2008 Sep;28(5):520-7. doi: 10.1007/s10875-008-9207-2. Epub 2008 Jun 28.
32	Immunological differences between primary and metastatic breast cancer.Ann Oncol. 2018 Nov 1;29(11):2232-2239. doi: 10.1093/annonc/mdy399.
33	Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression.Blood. 2011 Mar 10;117(10):2891-900. doi: 10.1182/blood-2009-12-253419. Epub 2011 Jan 11.
34	Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
35	Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
36	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.
37	Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.