Details of Drug Off-Target (DOT)

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

DOT Name	Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1)
Synonyms	CD158 antigen-like family member E; HLA-BW4-specific inhibitory NK cell receptor; Natural killer-associated transcript 3; NKAT-3; p70 natural killer cell receptor clones CL-2/CL-11; p70 NK receptor CL-2/CL-11; CD antigen CD158e
Gene Name	KIR3DL1
Related Disease	Acute lymphocytic leukaemia ( ) Adult lymphoma ( ) Advanced cancer ( ) Autoimmune hepatitis ( ) Breast cancer ( ) Breast carcinoma ( ) Childhood acute lymphoblastic leukemia ( ) Coeliac disease ( ) Epstein barr virus infection ( ) Graves disease ( ) Head-neck squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Hirschsprung disease ( ) Idiopathic thrombocytopenic purpura ( ) Latent tuberculosis infection ( ) Lupus ( ) Lymphoma ( ) Malaria ( ) Neoplasm ( ) Paroxysmal nocturnal haemoglobinuria ( ) Pediatric lymphoma ( ) Psoriasis ( ) Squamous cell carcinoma ( ) Systemic sclerosis ( ) Uveitis ( ) Cryohydrocytosis ( ) Human papillomavirus infection ( ) Liver cirrhosis ( ) Melanoma ( ) Pulmonary tuberculosis ( ) Spondyloarthropathy ( ) Tuberculosis ( ) Chronic renal failure ( ) End-stage renal disease ( ) Psoriatic arthritis ( ) Aplastic anemia ( ) Colorectal carcinoma ( ) Hepatitis B virus infection ( ) leukaemia ( ) Leukemia ( ) Neuroblastoma ( ) Non-insulin dependent diabetes ( )
UniProt ID	KI3L1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3VH8; 3WUW; 5B38; 5B39; 5T6Z; 5T70; 6V3J; 7K80; 7K81
Pfam ID	PF00047
Sequence	MSLMVVSMACVGLFLVQRAGPHMGGQDKPFLSAWPSAVVPRGGHVTLRCHYRHRFNNFML YKEDRIHIPIFHGRIFQESFNMSPVTTAHAGNYTCRGSHPHSPTGWSAPSNPVVIMVTGN HRKPSLLAHPGPLVKSGERVILQCWSDIMFEHFFLHKEGISKDPSRLVGQIHDGVSKANF SIGPMMLALAGTYRCYGSVTHTPYQLSAPSDPLDIVVTGPYEKPSLSAQPGPKVQAGESV TLSCSSRSSYDMYHLSREGGAHERRLPAVRKVNRTFQADFPLGPATHGGTYRCFGSFRHS PYEWSDPSDPLLVSVTGNPSSSWPSPTEPSSKSGNPRHLHILIGTSVVIILFILLLFFLL HLWCSNKKNAAVMDQEPAGNRTANSEDSDEQDPEEVTYAQLDHCVFTQRKITRPSQRPKT PPTDTILYTELPNAKPRSKVVSCP
Function	Receptor on natural killer (NK) cells for HLA Bw4 allele. Inhibits the activity of NK cells thus preventing cell lysis.
KEGG Pathway	Antigen processing and presentation (hsa04612 ) .tural killer cell mediated cytotoxicity (hsa04650 ) Graft-versus-host disease (hsa05332 )
Reactome Pathway	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[6]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[7]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[8]
Graves disease	DISU4KOQ	Strong	Biomarker	[9]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Hirschsprung disease	DISUUSM1	Strong	Genetic Variation	[12]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Genetic Variation	[13]
Latent tuberculosis infection	DIS6R1EH	Strong	Genetic Variation	[14]
Lupus	DISOKJWA	Strong	Altered Expression	[15]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[2]
Malaria	DISQ9Y50	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[17]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Strong	Genetic Variation	[18]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[2]
Psoriasis	DIS59VMN	Strong	Biomarker	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[20]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[21]
Uveitis	DISV0RYS	Strong	Biomarker	[22]
Cryohydrocytosis	DISMQHL3	moderate	Genetic Variation	[23]
Human papillomavirus infection	DISX61LX	moderate	Biomarker	[24]
Liver cirrhosis	DIS4G1GX	moderate	Genetic Variation	[25]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[26]
Pulmonary tuberculosis	DIS6FLUM	moderate	Genetic Variation	[27]
Spondyloarthropathy	DISBPYCZ	moderate	Biomarker	[28]
Tuberculosis	DIS2YIMD	moderate	Biomarker	[29]
Chronic renal failure	DISGG7K6	Disputed	Biomarker	[30]
End-stage renal disease	DISXA7GG	Disputed	Biomarker	[30]
Psoriatic arthritis	DISLWTG2	Disputed	Biomarker	[31]
Aplastic anemia	DISJRSC0	Limited	Biomarker	[32]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[33]
Hepatitis B virus infection	DISLQ2XY	Limited	Biomarker	[34]
leukaemia	DISS7D1V	Limited	Genetic Variation	[35]
Leukemia	DISNAKFL	Limited	Genetic Variation	[35]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[36]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[37]
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⏷ Show the Full List of 42 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1).	[41]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1).	[39]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1).	[42]
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References

1	Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide.Leukemia. 2019 Jan;33(1):230-239. doi: 10.1038/s41375-018-0170-5. Epub 2018 Jun 15.
2	Genetic diversity of the KIR/HLA system and susceptibility to hepatitis C virus-related diseases.PLoS One. 2015 Feb 20;10(2):e0117420. doi: 10.1371/journal.pone.0117420. eCollection 2015.
3	KIR downregulation by IL-12/15/18 unleashes human NK cells from KIR/HLA-I inhibition and enhances killing of tumor cells.Eur J Immunol. 2018 Feb;48(2):355-365. doi: 10.1002/eji.201747128. Epub 2017 Nov 29.
4	The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes.Genes Immun. 2016 Apr;17(3):187-92. doi: 10.1038/gene.2016.7. Epub 2016 Feb 18.
5	Association of the genetic diversity of killer cell immunoglobulin-like receptor genes and HLA-C ligand in Saudi women with breast cancer.Immunogenetics. 2017 Feb;69(2):69-76. doi: 10.1007/s00251-016-0950-x. Epub 2016 Sep 15.
6	Genetic associations of killer immunoglobulin like receptors and class I human leukocyte antigens on childhood acute lymphoblastic leukemia among north Indians.Hum Immunol. 2016 Jan;77(1):41-46. doi: 10.1016/j.humimm.2015.10.009. Epub 2015 Oct 21.
7	Contribution of KIR genes, HLA class I ligands, and KIR/HLA class I ligand combinations on the genetic predisposition to celiac disease and coexisting celiac disease and type 1 diabetes mellitus.Rev Esp Enferm Dig. 2015 Sep;107(9):547-53. doi: 10.17235/reed.2015.3817/2015.
8	Epstein-Barr virus infections are strongly dependent on activating and inhibitory KIR-HLA pairs after T-cell replate unrelated hematopoietic stem cell transplantation, the principles, and method of pairing analysis.HLA. 2019 Dec;94 Suppl 2:40-48. doi: 10.1111/tan.13770.
9	NKG2A expression and impaired function of NK cells in patients with new onset of Graves' disease.Int Immunopharmacol. 2015 Jan;24(1):133-9. doi: 10.1016/j.intimp.2014.09.020. Epub 2014 Oct 1.
10	Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma.Head Neck. 2019 Aug;41(8):2591-2601. doi: 10.1002/hed.25726. Epub 2019 Mar 4.
11	Human liver-derived CXCR6(+) NK cells are predominantly educated through NKG2A and show reduced cytokine production.J Leukoc Biol. 2019 Jun;105(6):1331-1340. doi: 10.1002/JLB.1MA1118-428R. Epub 2019 Feb 19.
12	Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2694-9. doi: 10.1073/pnas.0809630105. Epub 2009 Feb 5.
13	A Study of Human Killer Cell Immunoglobulin-Like Receptor and Multidrug Resistance Gene Polymorphisms in Children With Immune Thrombocytopenia.Clin Appl Thromb Hemost. 2016 Jul;22(5):429-40. doi: 10.1177/1076029615576738. Epub 2015 Mar 18.
14	Killer cell immunoglobulin like receptor gene association with tuberculosis.Hum Immunol. 2013 Jan;74(1):85-92. doi: 10.1016/j.humimm.2012.10.006. Epub 2012 Oct 13.
15	CD4+CD28+KIR+CD11a(hi) T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients.J Autoimmun. 2018 Jan;86:19-28. doi: 10.1016/j.jaut.2017.09.011. Epub 2017 Oct 20.
16	Killer cell immunoglobulin-like receptor (KIR) gene diversity in a population naturally exposed to malaria in Porto Velho, Northern Brazil.Tissue Antigens. 2015 Mar;85(3):190-9. doi: 10.1111/tan.12523. Epub 2015 Feb 6.
17	Imbalance of Genes Encoding Natural Killer Immunoglobulin-Like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer.Gastroenterology. 2019 Oct;157(4):1067-1080.e9. doi: 10.1053/j.gastro.2019.06.023. Epub 2019 Jun 21.
18	Killer immunoglobulin-like receptors (KIR) and their HLA-ligands in Italian paroxysmal nocturnal haemoglobinuria (PNH) patients.Tissue Antigens. 2012 Oct;80(4):322-7. doi: 10.1111/j.1399-0039.2012.01932.x. Epub 2012 Jul 17.
19	The Presence of HLA-A Bw4-80I KIR Ligands Could Predict "Difficult-to-Treat" Psoriasis and Poor Response to Etanercept.Mol Diagn Ther. 2018 Aug;22(4):471-474. doi: 10.1007/s40291-018-0345-9.
20	SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor-derived keratinocytes.Oncotarget. 2017 Apr 11;8(15):24652-24667. doi: 10.18632/oncotarget.15629.
21	Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis.Clin Rheumatol. 2017 Apr;36(4):853-862. doi: 10.1007/s10067-016-3526-0. Epub 2017 Jan 24.
22	Diversity of killer cell immunoglobulin-like receptor genes in uveitis associated with autoimmune diseases: ankylosing spondylitis and Behet disease.Ocul Immunol Inflamm. 2013 Apr;21(2):135-43. doi: 10.3109/09273948.2012.754905.
23	Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population.Int J Immunogenet. 2019 Aug;46(4):263-273. doi: 10.1111/iji.12425. Epub 2019 Apr 1.
24	Implication of HLA-C and KIR alleles in human papillomavirus infection and associated cervical lesions.Viral Immunol. 2014 Nov;27(9):468-70. doi: 10.1089/vim.2014.0017. Epub 2014 Sep 4.
25	KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians.PLoS One. 2017 Nov 17;12(11):e0188307. doi: 10.1371/journal.pone.0188307. eCollection 2017.
26	KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis.Immunogenetics. 2013 May;65(5):333-43. doi: 10.1007/s00251-013-0682-0. Epub 2013 Jan 31.
27	Potential implication of activating killer cell immunoglobulin-like receptor and HLA in onset of pulmonary tuberculosis.Scand J Immunol. 2012 Nov;76(5):491-6. doi: 10.1111/j.1365-3083.2012.02762.x.
28	Killer immunoglobulin-like receptor genes in uveitis.Ocul Immunol Inflamm. 2011 Jun;19(3):192-201. doi: 10.3109/09273948.2010.538798.
29	Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population.Tuberculosis (Edinb). 2015 Dec;95(6):817-821. doi: 10.1016/j.tube.2015.09.003. Epub 2015 Oct 17.
30	Putative role of KIR3DL1/3DS1 alleles and HLA-Bw4 ligands with end stage renal disease and long term renal allograft survival.Gene. 2017 Dec 30;637:219-229. doi: 10.1016/j.gene.2017.09.033. Epub 2017 Sep 21.
31	Association of variably expressed KIR3dl1 alleles with psoriatic disease.Clin Rheumatol. 2017 Oct;36(10):2261-2266. doi: 10.1007/s10067-017-3784-5. Epub 2017 Aug 11.
32	Impact of immunogenetic polymorphisms in bone marrow failure syndromes.Mini Rev Med Chem. 2011 Jun;11(6):544-52. doi: 10.2174/138955711795843356.
33	KIR genes and HLA class I ligands in a Caucasian Brazilian population with colorectal cancer.Hum Immunol. 2017 Mar;78(3):263-268. doi: 10.1016/j.humimm.2017.01.003. Epub 2017 Jan 11.
34	Insights into the Interplay between KIR Gene Frequencies and Chronic HBV Infection in Burkina Faso.Mediterr J Hematol Infect Dis. 2018 Nov 1;10(1):e2018060. doi: 10.4084/MJHID.2018.060. eCollection 2018.
35	Natural Killer Cells Offer Differential Protection From Leukemia in Chinese Southern Han.Front Immunol. 2019 Jul 16;10:1646. doi: 10.3389/fimmu.2019.01646. eCollection 2019.
36	KIR3DL1 Allelic Polymorphism and HLA-B Epitopes Modulate Response to Anti-GD2 Monoclonal Antibody in Patients With Neuroblastoma.J Clin Oncol. 2016 Jul 20;34(21):2443-51. doi: 10.1200/JCO.2015.64.9558. Epub 2016 Apr 11.
37	Diversity and association of HLA/KIR receptors with type 2 diabetes in South India.Int J Immunogenet. 2019 Jun;46(3):166-178. doi: 10.1111/iji.12417. Epub 2019 Feb 27.
38	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.
39	Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
40	DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors. Clin Immunol. 2009 Feb;130(2):213-24. doi: 10.1016/j.clim.2008.08.009. Epub 2008 Oct 22.
41	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.
42	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.