Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ15VVK)

DOT Name Interleukin-34 (IL34)
Synonyms IL-34
Gene Name IL34
Related Disease
Alzheimer disease ( )
Chronic kidney disease ( )
Periodontitis ( )
Acute myocardial infarction ( )
Adult glioblastoma ( )
Arteriosclerosis ( )
Arthritis ( )
Atherosclerosis ( )
Autoimmune disease ( )
B-cell lymphoma ( )
Cardiac failure ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Coronary atherosclerosis ( )
Crohn disease ( )
Diabetic kidney disease ( )
Endometriosis ( )
Glioblastoma multiforme ( )
Hepatitis ( )
Hepatitis B virus infection ( )
Huntington disease ( )
Inflammatory bowel disease ( )
Knee osteoarthritis ( )
Lung cancer ( )
Lung carcinoma ( )
Lupus ( )
Lymphoma ( )
Major depressive disorder ( )
Myocardial infarction ( )
Obesity ( )
Osteoarthritis ( )
Osteoporosis ( )
Polycystic ovarian syndrome ( )
Pulmonary disease ( )
Skin cancer ( )
Stroke ( )
Systemic lupus erythematosus ( )
Systemic sclerosis ( )
Ulcerative colitis ( )
Lupus nephritis ( )
Plasma cell myeloma ( )
Congenital contractural arachnodactyly ( )
Coronary heart disease ( )
Hepatocellular carcinoma ( )
Melanoma ( )
Rheumatoid arthritis ( )
UniProt ID
IL34_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4DKC; 4DKD; 4DKE; 4DKF
Pfam ID
PF15036
Sequence
MPRGFTWLRYLGIFLGVALGNEPLEMWPLTQNEECTVTGFLRDKLQYRSRLQYMKHYFPI
NYKISVPYEGVFRIANVTRLQRAQVSERELRYLWVLVSLSATESVQDVLLEGHPSWKYLQ
EVETLLLNVQQGLTDVEVSPKVESVLSLLNAPGPNLKLVRPKALLDNCFRVMELLYCSCC
KQSSVLNWQDCEVPSPQSCSPEPSLQYAATQLYPPPPWSPSSPPHSTGSVRPVRAQGEGL
LP
Function
Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.
Tissue Specificity
Detected in the sinusoidal epithelium in the red pulp of spleen (at protein level). Predominantly expressed in spleen. Also detected in a range of other tissues including heart, brain, lung, liver, kidney, thymus, testis, ovary, small intestine, prostate and colon.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
Reactome Pathway
Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350 )
Other interleukin signaling (R-HSA-449836 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Definitive Genetic Variation [1]
Chronic kidney disease DISW82R7 Definitive Biomarker [2]
Periodontitis DISI9JOI Definitive Biomarker [3]
Acute myocardial infarction DISE3HTG Strong Biomarker [4]
Adult glioblastoma DISVP4LU Strong Biomarker [5]
Arteriosclerosis DISK5QGC Strong Biomarker [6]
Arthritis DIST1YEL Strong Altered Expression [7]
Atherosclerosis DISMN9J3 Strong Biomarker [6]
Autoimmune disease DISORMTM Strong Biomarker [8]
B-cell lymphoma DISIH1YQ Strong Altered Expression [9]
Cardiac failure DISDC067 Strong Altered Expression [4]
Colon cancer DISVC52G Strong Biomarker [10]
Colon carcinoma DISJYKUO Strong Biomarker [10]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [10]
Congestive heart failure DIS32MEA Strong Altered Expression [4]
Coronary atherosclerosis DISKNDYU Strong Biomarker [11]
Crohn disease DIS2C5Q8 Strong Altered Expression [12]
Diabetic kidney disease DISJMWEY Strong Genetic Variation [13]
Endometriosis DISX1AG8 Strong Biomarker [14]
Glioblastoma multiforme DISK8246 Strong Biomarker [5]
Hepatitis DISXXX35 Strong Biomarker [15]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [16]
Huntington disease DISQPLA4 Strong Biomarker [17]
Inflammatory bowel disease DISGN23E Strong Altered Expression [12]
Knee osteoarthritis DISLSNBJ Strong Altered Expression [18]
Lung cancer DISCM4YA Strong Altered Expression [19]
Lung carcinoma DISTR26C Strong Altered Expression [19]
Lupus DISOKJWA Strong Altered Expression [20]
Lymphoma DISN6V4S Strong Biomarker [9]
Major depressive disorder DIS4CL3X Strong Altered Expression [21]
Myocardial infarction DIS655KI Strong Altered Expression [4]
Obesity DIS47Y1K Strong Altered Expression [6]
Osteoarthritis DIS05URM Strong Altered Expression [18]
Osteoporosis DISF2JE0 Strong Biomarker [22]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [23]
Pulmonary disease DIS6060I Strong Biomarker [24]
Skin cancer DISTM18U Strong Altered Expression [25]
Stroke DISX6UHX Strong Altered Expression [4]
Systemic lupus erythematosus DISI1SZ7 Strong Altered Expression [20]
Systemic sclerosis DISF44L6 Strong Altered Expression [26]
Ulcerative colitis DIS8K27O Strong Altered Expression [12]
Lupus nephritis DISCVGPZ moderate Biomarker [27]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [28]
Congenital contractural arachnodactyly DISOM1K7 Limited Biomarker [29]
Coronary heart disease DIS5OIP1 Limited Altered Expression [6]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [30]
Melanoma DIS1RRCY Limited Genetic Variation [31]
Rheumatoid arthritis DISTSB4J Limited Altered Expression [32]
------------------------------------------------------------------------------------
⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) 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 Interleukin-34 (IL34). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Interleukin-34 (IL34). [39]
------------------------------------------------------------------------------------
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Interleukin-34 (IL34). [34]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Interleukin-34 (IL34). [35]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Interleukin-34 (IL34). [36]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Interleukin-34 (IL34). [37]
APR-246 DMNFADH Phase 2 APR-246 affects the expression of Interleukin-34 (IL34). [38]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Interleukin-34 (IL34). [40]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Drug(s)

References

1 Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.Alzheimers Dement. 2018 May;14(5):623-633. doi: 10.1016/j.jalz.2017.11.006. Epub 2017 Dec 20.
2 Increased Serum Interleukin-34 Levels Are Related to the Presence and Severity of Cardiac Dysfunction in Patients With Ischemic Cardiomyopathy.Front Physiol. 2018 Jul 11;9:904. doi: 10.3389/fphys.2018.00904. eCollection 2018.
3 Expression of colony-stimulating factor 1 and interleukin-34 in gingival tissue and gingival fibroblasts from periodontitis patients and controls.J Periodontol. 2020 Jun;91(6):828-835. doi: 10.1002/JPER.19-0296. Epub 2020 Jan 20.
4 Interleukin-34 Levels Were Associated with Prognosis in Patients with Acute Myocardial Infarction.Int Heart J. 2019 Nov 30;60(6):1259-1267. doi: 10.1536/ihj.19-111. Epub 2019 Nov 15.
5 Receptor-type protein-tyrosine phosphatase is a functional receptor for interleukin-34.J Biol Chem. 2013 Jul 26;288(30):21972-86. doi: 10.1074/jbc.M112.442731. Epub 2013 Jun 6.
6 IL-34 promotes foam cell formation by enhancing CD36 expression through p38 MAPK pathway.Sci Rep. 2018 Nov 26;8(1):17347. doi: 10.1038/s41598-018-35485-2.
7 Serum levels of interleukin-34 and clinical correlation in patients with primary Sjgren's syndrome.Int J Rheum Dis. 2020 Mar;23(3):374-380. doi: 10.1111/1756-185X.13773. Epub 2019 Dec 10.
8 Immunomodulation of Interleukin-34 and its Potential Significance as a Disease Biomarker and Therapeutic Target.Int J Biol Sci. 2019 Jul 20;15(9):1835-1845. doi: 10.7150/ijbs.35070. eCollection 2019.
9 Expression of IL-34 correlates with macrophage infiltration and prognosis of diffuse large B-cell lymphoma.Clin Transl Immunology. 2019 Aug 13;8(8):e1074. doi: 10.1002/cti2.1074. eCollection 2019.
10 Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue.Oncotarget. 2017 Dec 15;9(3):3432-3445. doi: 10.18632/oncotarget.23289. eCollection 2018 Jan 9.
11 Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.J Am Heart Assoc. 2017 Apr 1;6(4):e004911. doi: 10.1161/JAHA.116.004911.
12 Interleukin-34 sustains inflammatory pathways in the gut.Clin Sci (Lond). 2015 Aug;129(3):271-80. doi: 10.1042/CS20150132.
13 Identified single-nucleotide polymorphisms and haplotypes at 16q22.1 increase diabetic nephropathy risk in Han Chinese population.BMC Genet. 2014 Oct 31;15:113. doi: 10.1186/s12863-014-0113-8.
14 Autocrine Production of Interleukin-34 Promotes the Development of Endometriosis through CSF1R/JAK3/STAT6 signaling.Sci Rep. 2019 Nov 14;9(1):16781. doi: 10.1038/s41598-019-52741-1.
15 Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis.Pathol Res Pract. 2019 Aug;215(8):152493. doi: 10.1016/j.prp.2019.152493. Epub 2019 Jun 10.
16 Interleukin-34 mediated by hepatitis B virus X protein via CCAAT/enhancer-binding protein contributes to the proliferation and migration of hepatoma cells.Cell Prolif. 2019 Nov;52(6):e12703. doi: 10.1111/cpr.12703. Epub 2019 Oct 16.
17 IKK and mutant huntingtin interactions regulate the expression of IL-34: implications for microglial-mediated neurodegeneration in HD.Hum Mol Genet. 2017 Nov 1;26(21):4267-4277. doi: 10.1093/hmg/ddx315.
18 Interleukin-34 as a promising clinical biomarker and therapeutic target for inflammatory arthritis.Cytokine Growth Factor Rev. 2019 Jun;47:43-53. doi: 10.1016/j.cytogfr.2019.05.005. Epub 2019 May 10.
19 High co-expression of IL-34 and M-CSF correlates with tumor progression and poor survival in lung cancers.Sci Rep. 2018 Jan 11;8(1):418. doi: 10.1038/s41598-017-18796-8.
20 Targeting IL-34 in inflammatory autoimmune diseases.J Cell Physiol. 2019 Dec;234(12):21810-21816. doi: 10.1002/jcp.28946. Epub 2019 Jun 7.
21 Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: An exploratory pilot case-control study.J Affect Disord. 2018 Nov;240:88-98. doi: 10.1016/j.jad.2018.07.040. Epub 2018 Jul 17.
22 Effect of Interleukin-34 on Secretion of Angiogenesis Cytokines by Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis.Immunol Invest. 2020 Feb;49(1-2):81-87. doi: 10.1080/08820139.2019.1649281. Epub 2019 Aug 12.
23 Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
24 IL-34 regulates IL-6 and IL-8 production in human lung fibroblasts via MAPK, PI3K-Akt, JAK and NF-B signaling pathways.Int Immunopharmacol. 2018 Aug;61:119-125. doi: 10.1016/j.intimp.2018.05.023. Epub 2018 May 30.
25 Integrative genomic analyses of a novel cytokine, interleukin-34 and its potential role in cancer prediction.Int J Mol Med. 2015 Jan;35(1):92-102. doi: 10.3892/ijmm.2014.2001. Epub 2014 Nov 12.
26 Serum interleukin-34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease.J Dermatol. 2018 Oct;45(10):1216-1220. doi: 10.1111/1346-8138.14538. Epub 2018 Jul 13.
27 Analysis of expression levels of IL-17 and IL-34 and influencing factors for prognosis in patients with lupus nephritis.Exp Ther Med. 2019 Mar;17(3):2279-2283. doi: 10.3892/etm.2019.7168. Epub 2019 Jan 14.
28 A role for IL-34 in osteolytic disease of multiple myeloma.Blood Adv. 2019 Feb 26;3(4):541-551. doi: 10.1182/bloodadvances.2018020008.
29 Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages.J Hepatol. 2017 Jan;66(1):102-115. doi: 10.1016/j.jhep.2016.08.012. Epub 2016 Sep 1.
30 High serum interleukin-34 level is a predictor of poor prognosis in patients with non-viral hepatocellular carcinoma.Hepatol Res. 2019 Sep;49(9):1046-1053. doi: 10.1111/hepr.13350. Epub 2019 May 29.
31 The RUNX1/IL-34/CSF-1R axis is an autocrinally regulated modulator of resistance to BRAF-V600E inhibition in melanoma.JCI Insight. 2018 Jul 26;3(14):e120422. doi: 10.1172/jci.insight.120422. eCollection 2018 Jul 26.
32 The correlation between interleukin-34 and bone erosion under ultrasound in rheumatoid arthritis.Mod Rheumatol. 2020 Mar;30(2):269-275. doi: 10.1080/14397595.2019.1593576. Epub 2019 Apr 16.
33 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.
34 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
35 Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
36 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
37 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
38 Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
39 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.
40 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.