Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT09FZE1)

• DOT Name: Killer cell immunoglobulin-like receptor 2DL5A (KIR2DL5A)
• Synonyms: CD antigen CD158f1
• Gene Name: KIR2DL5A
• Related Disease:
  Multiple sclerosis
  Ankylosing spondylitis
  Coeliac disease
  Cytomegalovirus infection
  Hepatitis C virus infection
  Inflammatory bowel disease
  Irritable bowel syndrome
  Non-hodgkin lymphoma
  Psoriasis
  Systemic lupus erythematosus
  Head-neck squamous cell carcinoma
  Neurofibromatosis type 1
  Small lymphocytic lymphoma
  Rheumatoid arthritis
  Type-1 diabetes
• UniProt ID: KI2LA_HUMAN
• Pfam ID: PF00047
• Sequence:
  MSLMVISMACVGFFLLQGAWTHEGGQDKPLLSAWPSAVVPRGGHVTLLCRSRLGFTIFSL
  YKEDGVPVPELYNKIFWKSILMGPVTPAHAGTYRCRGSHPRSPIEWSAPSNPLVIVVTGL
  FGKPSLSAQPGPTVRTGENVTLSCSSRSSFDMYHLSREGRAHEPRLPAVPSVNGTFQADF
  PLGPATHGGTYTCFGSLHDSPYEWSDPSDPLLVSVTGNSSSSSSSPTEPSSKTGIRRHLH
  ILIGTSVAIILFIILFFFLLHCCCSNKKNAAVMDQEPAGDRTVNREDSDDQDPQEVTYAQ
  LDHCVFTQTKITSPSQRPKTPPTDTTMYMELPNAKPRSLSPAHKHHSQALRGSSRETTAL
  SQNRVASSHVPAAGI
• Function: Receptor on natural killer (NK) cells for HLA-C alleles. 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)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[1]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[2]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[3]
Cytomegalovirus infection	DISCEMGC	Strong	Genetic Variation	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[5]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[6]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[6]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[7]
Psoriasis	DIS59VMN	Strong	Altered Expression	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[9]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[10]
Neurofibromatosis type 1	DIS53JH9	moderate	Biomarker	[11]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[12]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[13]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[14]

1 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 2DL5A (KIR2DL5A).	[15]

References

• [1] Killer cell immunoglobulin-like receptor genes in Spanish multiple sclerosis patients.Mol Immunol. 2011 Sep;48(15-16):1896-902. doi: 10.1016/j.molimm.2011.05.018. Epub 2011 Jun 12.
• [2] Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese.Int J Mol Sci. 2017 Aug 16;18(8):1775. doi: 10.3390/ijms18081775.
• [3] Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4.Genes Immun. 2007 Mar;8(2):171-6. doi: 10.1038/sj.gene.6364367. Epub 2007 Jan 11.
• [4] Killer immunoglobulin-like receptor gene repertoire influences viral load of primary human cytomegalovirus infection in renal transplant patients.Genes Immun. 2014 Dec;15(8):562-8. doi: 10.1038/gene.2014.53. Epub 2014 Sep 25.
• [5] Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders.Liver Int. 2010 Apr;30(4):567-73. doi: 10.1111/j.1478-3231.2010.02212.x.
• [6] Killer immunoglobulin-like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease.Microbiol Immunol. 2016 Nov;60(11):787-792. doi: 10.1111/1348-0421.12447.
• [7] Natural killer cell killer immunoglobulin-like gene receptor polymorphisms in non-Hodgkin lymphoma: possible association with clinical course.Leuk Lymphoma. 2015;56(10):2902-7. doi: 10.3109/10428194.2015.1014361. Epub 2015 Mar 27.
• [8] Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to psoriasis vulgaris.J Invest Dermatol. 2004 May;122(5):1133-6. doi: 10.1111/j.0022-202X.2004.22517.x.
• [9] Association between killer cell immunoglobulin-like receptor (KIR) polymorphisms and systemic lupus erythematosus (SLE) in populations: A PRISMA-compliant meta-analysis.Medicine (Baltimore). 2017 Mar;96(10):e6166. doi: 10.1097/MD.0000000000006166.
• [10] KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.Exp Mol Pathol. 2020 Feb;112:104345. doi: 10.1016/j.yexmp.2019.104345. Epub 2019 Nov 18.
• [11] KIR2DL5 mutation and loss underlies sporadic dermal neurofibroma pathogenesis and growth.Oncotarget. 2017 Jul 18;8(29):47574-47585. doi: 10.18632/oncotarget.17736.
• [12] KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease.Tissue Antigens. 2011 Aug;78(2):129-38. doi: 10.1111/j.1399-0039.2011.01721.x.
• [13] Association of Killer Cell Immunoglobulin- Like Receptor Genes in Iranian Patients with Rheumatoid Arthritis.PLoS One. 2015 Dec 11;10(12):e0143757. doi: 10.1371/journal.pone.0143757. eCollection 2015.
• [14] Predominance of the group A killer Ig-like receptor haplotypes in Korean patients with T1D.Ann N Y Acad Sci. 2006 Oct;1079:240-50. doi: 10.1196/annals.1375.037.
• [15] 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.