Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9XGA4G)

• DOT Name: Homeobox protein Hox-D11 (HOXD11)
• Synonyms: Homeobox protein Hox-4F
• Gene Name: HOXD11
• Related Disease:
  Bilateral renal agenesis
  Congenital anomaly of kidney and urinary tract
  Renal agenesis
  Renal hypodysplasia/aplasia 1
  Acute myelomonocytic leukemia M4
  Advanced cancer
  Autism
  Autism spectrum disorder
  Bone development disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Congenital deformities of limbs
  Ewing sarcoma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Male infertility
  Nephropathy
  Ovarian neoplasm
  Thrombocytopenia-absent radius syndrome
  Acute myelogenous leukaemia
  Neoplasm
  Ovarian cancer
  Rheumatoid arthritis
• UniProt ID: HXD11_HUMAN
• Pfam ID: PF12045 ; PF00046
• Sequence:
  MNDFDECGQSAASMYLPGCAYYVAPSDFASKPSFLSQPSSCQMTFPYSSNLAPHVQPVRE
  VAFRDYGLERAKWPYRGGGGGGSAGGGSSGGGPGGGGGGAGGYAPYYAAAAAAAAAAAAA
  EEAAMQRELLPPAGRRPDVLFKAPEPVCAAPGPPHGPAGAASNFYSAVGRNGILPQGFDQ
  FYEAAPGPPFAGPQPPPPPAPPQPEGAADKGDPRTGAGGGGGSPCTKATPGSEPKGAAEG
  SGGDGEGPPGEAGAEKSSSAVAPQRSRKKRCPYTKYQIRELEREFFFNVYINKEKRLQLS
  RMLNLTDRQVKIWFQNRRMKEKKLNRDRLQYFTGNPLF
• Function: Sequence-specific transcription factor which is 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

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bilateral renal agenesis	DISOR5IA	Definitive	Genetic Variation	[1]
Congenital anomaly of kidney and urinary tract	DIS84IVH	Definitive	Genetic Variation	[1]
Renal agenesis	DIS0M9AF	Definitive	Genetic Variation	[1]
Renal hypodysplasia/aplasia 1	DISOH8XN	Definitive	Genetic Variation	[1]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Autism	DISV4V1Z	Strong	Genetic Variation	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Bone development disease	DISVKAZS	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[7]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[8]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[9]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[9]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[10]
Male infertility	DISY3YZZ	Strong	Biomarker	[5]
Nephropathy	DISXWP4P	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Thrombocytopenia-absent radius syndrome	DIS5CVW9	Strong	Biomarker	[13]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[14]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[15]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[16]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein Hox-D11 (HOXD11).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Homeobox protein Hox-D11 (HOXD11).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Homeobox protein Hox-D11 (HOXD11).	[19]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Homeobox protein Hox-D11 (HOXD11).	[20]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Homeobox protein Hox-D11 (HOXD11).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein Hox-D11 (HOXD11).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-D11 (HOXD11).	[23]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein Hox-D11 (HOXD11).	[22]

References

• [1] Absence of mutations in the HOXA11 and HOXD11 genes in children with congenital renal malformations.Pediatr Nephrol. 2009 Aug;24(8):1569-72. doi: 10.1007/s00467-009-1140-y. Epub 2009 Mar 3.
• [2] Successful treatment of acute myelomonocytic leukaemia with NUP98-HOXD11 fusion transcripts and monitoring of minimal residual disease.Br J Haematol. 2003 Jan;120(2):274-6. doi: 10.1046/j.1365-2141.2003.04052.x.
• [3] Quantitative expression of the homeobox and integrin genes in human gastric carcinoma.Int J Mol Med. 2007 Oct;20(4):621-9.
• [4] Study of HOXD genes in autism particularly regarding the ratio of second to fourth digit length.Brain Dev. 2010 May;32(5):356-61. doi: 10.1016/j.braindev.2009.05.005. Epub 2009 Jun 18.
• [5] Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11.Development. 1994 Aug;120(8):2187-98. doi: 10.1242/dev.120.8.2187.
• [6] Identification of 20 genes aberrantly methylated in human breast cancers.Int J Cancer. 2005 Sep 1;116(3):407-14. doi: 10.1002/ijc.21054.
• [7] A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse.Development. 1996 Apr;122(4):1175-85. doi: 10.1242/dev.122.4.1175.
• [8] The posterior HOXD locus: Its contribution to phenotype and malignancy of Ewing sarcoma.Oncotarget. 2016 Jul 5;7(27):41767-41780. doi: 10.18632/oncotarget.9702.
• [9] POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer.Oncotarget. 2014 Sep 30;5(18):8803-15. doi: 10.18632/oncotarget.2492.
• [10] Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma.Int J Oncol. 2012 Apr;40(4):1180-8. doi: 10.3892/ijo.2011.1321. Epub 2011 Dec 29.
• [11] Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11.Nature. 1995 Jun 29;375(6534):791-5. doi: 10.1038/375791a0.
• [12] Identification of PRTFDC1 silencing and aberrant promoter methylation of GPR150, ITGA8 and HOXD11 in ovarian cancers.Life Sci. 2007 Mar 27;80(16):1458-65. doi: 10.1016/j.lfs.2007.01.015. Epub 2007 Jan 20.
• [13] Absence of mutations in the HoxA10, HoxA11 and HoxD11 nucleotide coding sequences in thrombocytopenia with absent radius syndrome.Br J Haematol. 2002 Feb;116(2):367-75. doi: 10.1046/j.1365-2141.2002.03263.x.
• [14] The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15).Cancer Res. 2002 Jan 1;62(1):33-7.
• [15] HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma.Tumour Biol. 2016 Nov;37(11):15087-15096. doi: 10.1007/s13277-016-5356-8. Epub 2016 Sep 22.
• [16] Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
• [17] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] 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.
• [20] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] 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.
• [23] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.