Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWSC8TF)

DOT Name	Homeobox protein Hox-D13 (HOXD13)
Synonyms	Homeobox protein Hox-4I
Gene Name	HOXD13
Related Disease	Brachydactyly-syndactyly syndrome ( ) Hyperglycemia ( ) Advanced cancer ( ) Anemia ( ) Asthma ( ) Brachydactyly ( ) Breast neoplasm ( ) Coagulation defect ( ) Colorectal carcinoma ( ) Endometrial carcinoma ( ) Esophageal cancer ( ) Fetal growth restriction ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Hypospadias ( ) Idiopathic thrombocytopenic purpura ( ) leukaemia ( ) Melanoma ( ) Myelodysplastic syndrome ( ) Non-small-cell lung cancer ( ) Obesity ( ) Osteoarthritis ( ) Parkinson disease ( ) Platelet storage pool deficiency ( ) Syndactyly ( ) Synpolydactyly type 1 ( ) Triple negative breast cancer ( ) VACTERL/vater association ( ) Cardiovascular disease ( ) Childhood myelodysplastic syndrome ( ) Lung cancer ( ) Lung carcinoma ( ) Thyroid gland papillary carcinoma ( ) Brachydactyly type E ( ) Syndactyly type 5 ( ) Neoplasm ( ) Rheumatoid arthritis ( ) Acute leukaemia ( ) Acute myelogenous leukaemia ( ) Cryptorchidism ( ) Hand-foot-genital syndrome ( ) Intellectual disability ( ) Leukemia ( ) Neuroblastoma ( ) Pancreatic cancer ( )
UniProt ID	HXD13_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00046 ; PF12284
Sequence	MSRAGSWDMDGLRADGGGAGGAPASSSSSSVAAAAASGQCRGFLSAPVFAGTHSGRAAAA AAAAAAAAAAASGFAYPGTSERTGSSSSSSSSAVVAARPEAPPAKECPAPTPAAAAAAPP SAPALGYGYHFGNGYYSCRMSHGVGLQQNALKSSPHASLGGFPVEKYMDVSGLASSSVPA NEVPARAKEVSFYQGYTSPYQHVPGYIDMVSTFGSGEPRHEAYISMEGYQSWTLANGWNS QVYCTKDQPQGSHFWKSSFPGDVALNQPDMCVYRRGRKKRVPYTKLQLKELENEYAINKF INKDKRRRISAATNLSERQVTIWFQNRRVKDKKIVSKLKDTVS
Function	Sequence-specific transcription factor that binds gene promoters and activates their transcription. Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Brachydactyly-syndactyly syndrome	DISR95WN	Definitive	Autosomal dominant	[1]
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Anemia	DISTVL0C	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Altered Expression	[5]
Brachydactyly	DIS2533F	Strong	Genetic Variation	[6]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[7]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[10]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[11]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Hypospadias	DIS48CCP	Strong	Biomarker	[15]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Biomarker	[17]
Melanoma	DIS1RRCY	Strong	Altered Expression	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[19]
Obesity	DIS47Y1K	Strong	Genetic Variation	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Parkinson disease	DISQVHKL	Strong	Biomarker	[22]
Platelet storage pool deficiency	DISHODOH	Strong	Genetic Variation	[23]
Syndactyly	DISZK2BT	Strong	Genetic Variation	[24]
Synpolydactyly type 1	DISAO4FJ	Strong	Autosomal dominant	[25]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[26]
VACTERL/vater association	DISJNE30	Strong	Biomarker	[27]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[28]
Childhood myelodysplastic syndrome	DISMN80I	moderate	Biomarker	[18]
Lung cancer	DISCM4YA	moderate	Biomarker	[9]
Lung carcinoma	DISTR26C	moderate	Biomarker	[9]
Thyroid gland papillary carcinoma	DIS48YMM	moderate	Altered Expression	[29]
Brachydactyly type E	DISM8YNM	Supportive	Autosomal dominant	[27]
Syndactyly type 5	DIS1KOY0	Supportive	Autosomal dominant	[30]
Neoplasm	DISZKGEW	Disputed	Biomarker	[31]
Rheumatoid arthritis	DISTSB4J	Disputed	Altered Expression	[32]
Acute leukaemia	DISDQFDI	Limited	Biomarker	[33]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[34]
Cryptorchidism	DISYUD2P	Limited	Biomarker	[35]
Hand-foot-genital syndrome	DISZQ3U9	Limited	Genetic Variation	[36]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[37]
Leukemia	DISNAKFL	Limited	Altered Expression	[38]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[39]
Pancreatic cancer	DISJC981	Limited	Biomarker	[40]
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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

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 Homeobox protein Hox-D13 (HOXD13).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein Hox-D13 (HOXD13).	[42]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-D13 (HOXD13).	[43]
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References

1	An acceptor splice site mutation in HOXD13 results in variable hand, but consistent foot malformations. Am J Med Genet A. 2003 Aug 15;121A(1):69-74. doi: 10.1002/ajmg.a.20103.
2	Maternal BDE-209 exposure during lactation causes testicular and epididymal toxicity through increased oxidative stress in peripubertal mice offspring.Toxicol Lett. 2019 Sep 1;311:66-79. doi: 10.1016/j.toxlet.2019.04.028. Epub 2019 Apr 27.
3	Association Between Activation of the Programmed Cell Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) Pathway and Pain in Patients with Cancer.Med Sci Monit. 2019 Feb 16;25:1275-1282. doi: 10.12659/MSM.912632.
4	Analysis of hematopathology and alteration of JAK1/STAT3/STAT5 signaling axis in experimental myelodysplastic syndrome.Chem Biol Interact. 2016 Dec 25;260:176-185. doi: 10.1016/j.cbi.2016.10.010. Epub 2016 Oct 8.
5	Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.Allergy. 2019 Jan;74(1):78-88. doi: 10.1111/all.13458. Epub 2018 Oct 22.
6	A homozygous HOXD13 missense mutation causes a severe form of synpolydactyly with metacarpal to carpal transformation.Am J Med Genet A. 2016 Mar;170(3):615-21. doi: 10.1002/ajmg.a.37464. Epub 2015 Nov 18.
7	HOXD13 methylation status is a prognostic indicator in breast cancer.Int J Clin Exp Pathol. 2015 Sep 1;8(9):10716-24. eCollection 2015.
8	Molecular determinants of platelet delta storage pool deficiencies: an update.Br J Haematol. 2013 Jan;160(1):5-11. doi: 10.1111/bjh.12064. Epub 2012 Oct 1.
9	Soluble PD-1-based vaccine targeting MUC1 VNTR and survivin improves anti-tumor effect.Immunol Lett. 2018 Aug;200:33-42. doi: 10.1016/j.imlet.2018.06.004. Epub 2018 Jun 9.
10	Chronic BDE-47 Exposure Aggravates Malignant Phenotypes and Chemoresistance by Activating ERK Through ER and GPR30 in Endometrial Carcinoma.Front Oncol. 2019 Oct 31;9:1079. doi: 10.3389/fonc.2019.01079. eCollection 2019.
11	Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer.Med Oncol. 2019 May 27;36(7):60. doi: 10.1007/s12032-019-1285-x.
12	Periodontal disease: Repercussions in pregnant woman and newborn health-A cohort study.PLoS One. 2019 Nov 22;14(11):e0225036. doi: 10.1371/journal.pone.0225036. eCollection 2019.
13	Aberrant production of soluble inducible T cell costimulator and soluble programmed cell death protein 1 in patients with chronic hepatitis B.Mol Med Rep. 2017 Dec;16(6):8556-8562. doi: 10.3892/mmr.2017.7630. Epub 2017 Sep 26.
14	The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma.Cancer Immunol Immunother. 2019 Mar;68(3):353-363. doi: 10.1007/s00262-018-2271-4. Epub 2018 Dec 1.
15	Maternal exposure to di-n-butyl phthalate (DBP) induces combined anorectal and urogenital malformations in male rat offspring.Reprod Toxicol. 2016 Jun;61:169-76. doi: 10.1016/j.reprotox.2016.04.007. Epub 2016 Apr 11.
16	PD-1/PD-L1 pathway activation restores the imbalance of Th1/Th2 and treg/Th17 cells subtypes in immune thrombocytopenic purpura patients.Medicine (Baltimore). 2019 Oct;98(43):e17608. doi: 10.1097/MD.0000000000017608.
17	Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation.Leukemia. 2000 Sep;14(9):1621-9. doi: 10.1038/sj.leu.2401881.
18	Leptin-deficient obesity prolongs survival in a murine model of myelodysplastic syndrome.Haematologica. 2018 Apr;103(4):597-606. doi: 10.3324/haematol.2017.181958. Epub 2018 Jan 25.
19	Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib.Lung Cancer. 2016 Oct;100:77-84. doi: 10.1016/j.lungcan.2016.08.001. Epub 2016 Aug 6.
20	In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis.Arch Toxicol. 2018 May;92(5):1847-1860. doi: 10.1007/s00204-018-2177-0. Epub 2018 Mar 9.
21	Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts.Arthritis Rheum. 1997 Sep;40(9):1628-35. doi: 10.1002/art.1780400912.
22	Study of metabolic disorders associated with BDE-47 exposure in Drosophila model by MS-based metabolomics.Ecotoxicol Environ Saf. 2019 Nov 30;184:109606. doi: 10.1016/j.ecoenv.2019.109606. Epub 2019 Aug 28.
23	Alpha-delta platelet storage pool deficiency in three generations.Platelets. 2007 Feb;18(1):1-10. doi: 10.1080/09537100600800172.
24	Exome sequencing identifies a novel nonsense mutation of HOXD13 in a Chinese family with synpolydactyly.Congenit Anom (Kyoto). 2017 Jan;57(1):4-7. doi: 10.1111/cga.12173.
25	Novel mutations of the HOXD13 gene in hand and foot malformations. Int Surg. 2007 Sep-Oct;92(5):287-95.
26	Serum sPD-1 and sPD-L1 as Biomarkers for Evaluating the Efficacy of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.Clin Breast Cancer. 2019 Oct;19(5):326-332.e1. doi: 10.1016/j.clbc.2019.03.008. Epub 2019 Apr 11.
27	Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E. Am J Hum Genet. 2003 Apr;72(4):984-97. doi: 10.1086/374721. Epub 2003 Mar 14.
28	Decarbromodiphenyl ether (BDE-209) promotes monocyte-endothelial adhesion in cultured human aortic endothelial cells through upregulating intercellular adhesion molecule-1.Environ Res. 2019 Feb;169:62-71. doi: 10.1016/j.envres.2018.10.035. Epub 2018 Nov 1.
29	Polybrominated Diphenyl Ethers, Polybrominated Biphenyls, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.Am J Epidemiol. 2020 Feb 28;189(2):120-132. doi: 10.1093/aje/kwz229.
30	Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome. Am J Hum Genet. 2007 Feb;80(2):361-71. doi: 10.1086/511387. Epub 2007 Jan 3.
31	Clinical significance of soluble programmed cell death-1 and soluble programmed cell death-ligand 1 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.PLoS One. 2019 Feb 26;14(2):e0212978. doi: 10.1371/journal.pone.0212978. eCollection 2019.
32	Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis.Clin Exp Med. 2019 Feb;19(1):55-64. doi: 10.1007/s10238-018-0530-5. Epub 2018 Oct 4.
33	Progressive genomic instability in the Nup98-HoxD13 model of MDS correlates with loss of the PIG-A gene product.Neoplasia. 2014 Aug;16(8):627-33. doi: 10.1016/j.neo.2014.07.004.
34	Thymic precursor cells generate acute myeloid leukemia in NUP98-PHF23/NUP98-HOXD13 double transgenic mice.Sci Rep. 2019 Nov 20;9(1):17213. doi: 10.1038/s41598-019-53610-7.
35	A Case-Control Study of Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Cryptorchidism in Canadian Populations.Environ Health Perspect. 2017 May 26;125(5):057004. doi: 10.1289/EHP522.
36	The pathophysiology of HOX genes and their role in cancer.J Pathol. 2005 Jan;205(2):154-71. doi: 10.1002/path.1710.
37	Sensorineural deafness, abnormal genitalia, synostosis of metacarpals and metatarsals 4 and 5, and mental retardation: description of a second patient and exclusion of HOXD13.Am J Med Genet A. 2005 Jun 1;135(2):211-3. doi: 10.1002/ajmg.a.30728.
38	Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in Nras, Kras, and Cbl.Blood. 2008 Sep 1;112(5):2017-9. doi: 10.1182/blood-2008-01-135186. Epub 2008 Jun 19.
39	Effect of Taurine on Alterations in Deiodinase 3 Expression Induced by BDE 209 in Human Neuroblasoma-Derived SK-N-AS Cells.Adv Exp Med Biol. 2019;1155:847-856. doi: 10.1007/978-981-13-8023-5_71.
40	Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer.Oncoimmunology. 2017 Mar 31;6(5):e1310358. doi: 10.1080/2162402X.2017.1310358. eCollection 2017.
41	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.
42	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.
43	Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.