Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA0UN4C)

DOT Name Pituitary homeobox 1 (PITX1)
Synonyms Hindlimb-expressed homeobox protein backfoot; Homeobox protein PITX1; Paired-like homeodomain transcription factor 1
Gene Name PITX1
Related Disease
Adult glioblastoma ( )
Gastric neoplasm ( )
Glioblastoma multiforme ( )
Knee osteoarthritis ( )
Androgen insensitivity syndrome ( )
Autism ( )
Breast cancer ( )
Breast carcinoma ( )
Clear cell renal carcinoma ( )
Clubfoot ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Congenital deformities of limbs ( )
Congestive heart failure ( )
Esophageal adenocarcinoma ( )
Esophageal squamous cell carcinoma ( )
facioscapulohumeral muscular dystrophy ( )
Gastric cancer ( )
Glioma ( )
Hepatitis C virus infection ( )
Immunodeficiency ( )
Influenza ( )
Laurin-Sandrow syndrome ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Neoplasm of testis ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Polydactyly ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Testicular germ cell tumor ( )
Cutaneous melanoma ( )
Gastritis ( )
Hepatocellular carcinoma ( )
Tuberous sclerosis ( )
Brachydactyly-elbow wrist dysplasia syndrome ( )
Adenocarcinoma ( )
Adenoma ( )
Advanced cancer ( )
Barrett esophagus ( )
Melanoma ( )
T-cell acute lymphoblastic leukaemia ( )
UniProt ID
PITX1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00046 ; PF03826
Sequence
MDAFKGGMSLERLPEGLRPPPPPPHDMGPAFHLARPADPREPLENSASESSDTELPEKER
GGEPKGPEDSGAGGTGCGGADDPAKKKKQRRQRTHFTSQQLQELEATFQRNRYPDMSMRE
EIAVWTNLTEPRVRVWFKNRRAKWRKRERNQQLDLCKGGYVPQFSGLVQPYEDVYAAGYS
YNNWAAKSLAPAPLSTKSFTFFNSMSPLSSQSMFSAPSSISSMTMPSSMGPGAVPGMPNS
GLNNINNLTGSSLNSAMSPGACPYGTPASPYSVYRDTCNSSLASLRLKSKQHSSFGYGGL
QGPASGLNACQYNS
Function
Sequence-specific transcription factor that binds gene promoters and activates their transcription. May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb.

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Definitive Altered Expression [1]
Gastric neoplasm DISOKN4Y Definitive Altered Expression [2]
Glioblastoma multiforme DISK8246 Definitive Altered Expression [1]
Knee osteoarthritis DISLSNBJ Definitive Genetic Variation [3]
Androgen insensitivity syndrome DISUZBBO Strong Altered Expression [4]
Autism DISV4V1Z Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [7]
Clubfoot DISLXT4S Strong Autosomal dominant [8]
Colon cancer DISVC52G Strong Genetic Variation [9]
Colon carcinoma DISJYKUO Strong Genetic Variation [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Congenital deformities of limbs DISP4N1Q Strong Genetic Variation [11]
Congestive heart failure DIS32MEA Strong Biomarker [12]
Esophageal adenocarcinoma DISODWFP Strong Altered Expression [13]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [14]
facioscapulohumeral muscular dystrophy DISSE0H0 Strong Biomarker [15]
Gastric cancer DISXGOUK Strong Altered Expression [16]
Glioma DIS5RPEH Strong Biomarker [17]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [18]
Immunodeficiency DIS093I0 Strong Genetic Variation [19]
Influenza DIS3PNU3 Strong Altered Expression [20]
Laurin-Sandrow syndrome DISOYBC3 Strong ChromosomalRearrangement [11]
Lung adenocarcinoma DISD51WR Strong Altered Expression [21]
Lung cancer DISCM4YA Strong Altered Expression [22]
Lung carcinoma DISTR26C Strong Altered Expression [22]
Neoplasm DISZKGEW Strong Altered Expression [23]
Neoplasm of testis DISK4XHT Strong Genetic Variation [24]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [23]
Osteoarthritis DIS05URM Strong Altered Expression [25]
Polydactyly DIS25BMZ Strong Genetic Variation [26]
Prostate cancer DISF190Y Strong Biomarker [27]
Prostate carcinoma DISMJPLE Strong Biomarker [27]
Prostate neoplasm DISHDKGQ Strong Biomarker [28]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [7]
Squamous cell carcinoma DISQVIFL Strong Biomarker [29]
Stomach cancer DISKIJSX Strong Altered Expression [16]
Testicular germ cell tumor DIS5RN24 Strong Biomarker [24]
Cutaneous melanoma DIS3MMH9 moderate Altered Expression [30]
Gastritis DIS8G07K moderate Biomarker [31]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [32]
Tuberous sclerosis DISEMUGZ moderate Genetic Variation [33]
Brachydactyly-elbow wrist dysplasia syndrome DIS9TZPZ Supportive Autosomal dominant [34]
Adenocarcinoma DIS3IHTY Limited Biomarker [35]
Adenoma DIS78ZEV Limited Biomarker [35]
Advanced cancer DISAT1Z9 Limited Altered Expression [16]
Barrett esophagus DIS416Y7 Limited Altered Expression [36]
Melanoma DIS1RRCY Limited Altered Expression [30]
T-cell acute lymphoblastic leukaemia DIS17AI2 Limited Altered Expression [37]
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⏷ Show the Full List of 50 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Pituitary homeobox 1 (PITX1). [38]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Pituitary homeobox 1 (PITX1). [49]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Pituitary homeobox 1 (PITX1). [50]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Pituitary homeobox 1 (PITX1). [39]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Pituitary homeobox 1 (PITX1). [40]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Pituitary homeobox 1 (PITX1). [41]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Pituitary homeobox 1 (PITX1). [42]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Pituitary homeobox 1 (PITX1). [43]
Triclosan DMZUR4N Approved Triclosan increases the expression of Pituitary homeobox 1 (PITX1). [44]
Selenium DM25CGV Approved Selenium increases the expression of Pituitary homeobox 1 (PITX1). [45]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Pituitary homeobox 1 (PITX1). [46]
Aspirin DM672AH Approved Aspirin increases the expression of Pituitary homeobox 1 (PITX1). [47]
Malathion DMXZ84M Approved Malathion decreases the expression of Pituitary homeobox 1 (PITX1). [48]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Pituitary homeobox 1 (PITX1). [51]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Pituitary homeobox 1 (PITX1). [52]
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⏷ Show the Full List of 12 Drug(s)

References

1 Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis.Eur J Pharmacol. 2019 Nov 15;863:172643. doi: 10.1016/j.ejphar.2019.172643. Epub 2019 Sep 4.
2 Expression of pituitary homeobox 1 gene in human gastric carcinogenesis and its clinicopathological significance.World J Gastroenterol. 2008 Jan 14;14(2):292-7. doi: 10.3748/wjg.14.292.
3 Genetic polymorphism of PITX1 in susceptibility to knee osteoarthritis in a Chinese Han population: a case-control study.Rheumatol Int. 2011 May;31(5):629-33. doi: 10.1007/s00296-009-1341-5. Epub 2010 Jan 7.
4 Abnormal PITX1 gene methylation in adolescent idiopathic scoliosis: a pilot study.BMC Musculoskelet Disord. 2018 May 9;19(1):138. doi: 10.1186/s12891-018-2054-2.
5 Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis.BMC Med Genet. 2007 Dec 6;8:74. doi: 10.1186/1471-2350-8-74.
6 The estrogen-regulated transcription factor PITX1 coordinates gene-specific regulation by estrogen receptor-alpha in breast cancer cells.Mol Endocrinol. 2011 Oct;25(10):1699-709. doi: 10.1210/me.2011-0102. Epub 2011 Aug 25.
7 Integrin 5 triggers the metastatic potential in renal cell carcinoma.Oncotarget. 2017 Nov 18;8(64):107530-107542. doi: 10.18632/oncotarget.22501. eCollection 2017 Dec 8.
8 Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation. Am J Hum Genet. 2008 Nov;83(5):616-22. doi: 10.1016/j.ajhg.2008.10.004. Epub 2008 Oct 23.
9 Interaction between physical activity, PITX1 rs647161 genetic polymorphism and colorectal cancer risk in a Korean population: a case-control study.Oncotarget. 2018 Jan 10;9(7):7590-7603. doi: 10.18632/oncotarget.24136. eCollection 2018 Jan 26.
10 The association between fecal enterotoxigenic B. fragilis with colorectal cancer.BMC Cancer. 2019 Sep 5;19(1):879. doi: 10.1186/s12885-019-6115-1.
11 Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly. Eur J Hum Genet. 2012 Jun;20(6):705-8. doi: 10.1038/ejhg.2011.264. Epub 2012 Jan 18.
12 Paediatric deaths in a tertiary government hospital setting, Malawi.Paediatr Int Child Health. 2019 Nov;39(4):240-248. doi: 10.1080/20469047.2018.1536873. Epub 2018 Nov 19.
13 Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma.Surgery. 2005 Nov;138(5):924-31. doi: 10.1016/j.surg.2005.05.007.
14 DNA hypermethyation and silencing of PITX1 correlated with advanced stage and poor postoperative prognosis of esophageal squamous cell carcinoma.Oncotarget. 2017 Sep 28;8(48):84434-84448. doi: 10.18632/oncotarget.21375. eCollection 2017 Oct 13.
15 Testing the effects of FSHD candidate gene expression in vertebrate muscle development.Int J Clin Exp Pathol. 2010 Mar 28;3(4):386-400.
16 Silenced PITX1 promotes chemotherapeutic resistance to 5-fluorocytosine and cisplatin in gastric cancer cells.Exp Ther Med. 2019 May;17(5):4046-4054. doi: 10.3892/etm.2019.7459. Epub 2019 Apr 1.
17 Elevation of circ-PITX1 upregulates interleukin 17 receptor D expression via sponging miR-518a-5p and facilitates cell progression in glioma.J Cell Biochem. 2019 Oct;120(10):16495-16502. doi: 10.1002/jcb.28868. Epub 2019 May 8.
18 Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1.Virology. 2003 Feb 1;306(1):51-9. doi: 10.1016/s0042-6822(02)00029-6.
19 bft gene subtyping in enterotoxigenic Bacteroides fragilis isolated from children with acute diarrhea.Anaerobe. 2007 Feb;13(1):1-5. doi: 10.1016/j.anaerobe.2006.10.002. Epub 2006 Dec 12.
20 Transcriptional derepression of the ERVWE1 locus following influenza A virus infection.J Virol. 2014 Apr;88(8):4328-37. doi: 10.1128/JVI.03628-13. Epub 2014 Jan 29.
21 High PITX1 expression in lung adenocarcinoma patients is associated with DNA methylation and poor prognosis.Pathol Res Pract. 2018 Dec;214(12):2046-2053. doi: 10.1016/j.prp.2018.09.025. Epub 2018 Sep 29.
22 Decreased PITX1 homeobox gene expression in human lung cancer.Lung Cancer. 2007 Mar;55(3):287-94. doi: 10.1016/j.lungcan.2006.11.001. Epub 2006 Dec 8.
23 MicroRNA-1204 promotes cell proliferation by regulating PITX1 in non-small-cell lung cancer.Cell Biol Int. 2019 Mar;43(3):253-264. doi: 10.1002/cbin.11083. Epub 2019 Jan 28.
24 Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.Nat Genet. 2013 Jun;45(6):686-9. doi: 10.1038/ng.2635. Epub 2013 May 12.
25 Overexpression of Pitx1 attenuates the senescence of chondrocytes from osteoarthritis degeneration cartilage-A self-controlled model for studying the etiology and treatment of osteoarthritis.Bone. 2020 Feb;131:115177. doi: 10.1016/j.bone.2019.115177. Epub 2019 Nov 27.
26 Exome sequencing revealed a novel loss-of-function variant in the GLI3 transcriptional activator 2 domain underlies nonsyndromic postaxial polydactyly.Mol Genet Genomic Med. 2019 Jul;7(7):e00627. doi: 10.1002/mgg3.627. Epub 2019 May 21.
27 PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer cell line PC-3.DNA Cell Biol. 2006 Sep;25(9):523-9. doi: 10.1089/dna.2006.25.523.
28 Effects of PTX1 expression on growth and tumorigenicity of the prostate cancer cell line PC-3.DNA Cell Biol. 2003 Jul;22(7):469-74. doi: 10.1089/104454903322247343.
29 De Novo PITX1 Expression Controls Bi-Stable Transcriptional Circuits to Govern Self-Renewal and Differentiation in Squamous Cell Carcinoma.Cell Stem Cell. 2019 Mar 7;24(3):390-404.e8. doi: 10.1016/j.stem.2019.01.003. Epub 2019 Jan 31.
30 Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma.Kaohsiung J Med Sci. 2016 Oct;32(10):494-500. doi: 10.1016/j.kjms.2016.08.001. Epub 2016 Aug 27.
31 Oral Helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA nanoparticles promote immune protection.Eur J Pharm Biopharm. 2017 Feb;111:33-43. doi: 10.1016/j.ejpb.2016.11.007. Epub 2016 Nov 16.
32 Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
33 Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings.Ophthalmology. 2012 Sep;119(9):1917-23. doi: 10.1016/j.ophtha.2012.03.020. Epub 2012 May 16.
34 Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus. Am J Hum Genet. 2012 Oct 5;91(4):629-35. doi: 10.1016/j.ajhg.2012.08.014. Epub 2012 Sep 27.
35 Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas.BMC Cancer. 2006 Oct 9;6:241. doi: 10.1186/1471-2407-6-241.
36 Hypersensitive IFN Responses in Lupus Keratinocytes Reveal Key Mechanistic Determinants in Cutaneous Lupus.J Immunol. 2019 Apr 1;202(7):2121-2130. doi: 10.4049/jimmunol.1800650. Epub 2019 Feb 11.
37 Activation of Paired-homeobox gene PITX1 by del(5)(q31) in T-cell acute lymphoblastic leukemia.Leuk Lymphoma. 2011 Jul;52(7):1348-59. doi: 10.3109/10428194.2011.566391. Epub 2011 Mar 22.
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 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
40 Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
41 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
42 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
43 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
44 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
45 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
46 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
47 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
48 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
49 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.
50 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
51 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
52 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.