Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGC0EKI)

• DOT Name: Homeobox protein Hox-B1 (HOXB1)
• Synonyms: Homeobox protein Hox-2I
• Gene Name: HOXB1
• Related Disease:
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Advanced cancer
  Bone osteosarcoma
  Campomelic dysplasia
  Carcinoma
  Congenital nervous system disorder
  Facial paresis, hereditary congenital, 3
  Glioblastoma multiforme
  Glioma
  leukaemia
  Leukemia
  Mobius syndrome
  Neoplasm
  Neuroblastoma
  Osteosarcoma
  Renal carcinoma
  Renal cell carcinoma
  Ventricular septal defect
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Ear malformation
  Congenital hereditary facial paralysis-variable hearing loss syndrome
  Acute myelogenous leukaemia
• UniProt ID: HXB1_HUMAN
• PDB ID: 1B72
• Pfam ID: PF00046
• Sequence:
  MDYNRMNSFLEYPLCNRGPSAYSAHSAPTSFPPSSAQAVDSYASEGRYGGGLSSPAFQQN
  SGYPAQQPPSTLGVPFPSSAPSGYAPAACSPSYGPSQYYPLGQSEGDGGYFHPSSYGAQL
  GGLSDGYGAGGAGPGPYPPQHPPYGNEQTASFAPAYADLLSEDKETPCPSEPNTPTARTF
  DWMKVKRNPPKTAKVSEPGLGSPSGLRTNFTTRQLTELEKEFHFNKYLSRARRVEIAATL
  ELNETQVKIWFQNRRMKQKKREREEGRVPPAPPGCPKEAAGDASDQSTCTSPEASPSSVT
  S
• 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. Acts on the anterior body structures.
• KEGG Pathway: Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Campomelic dysplasia	DISVTW53	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Congenital nervous system disorder	DIS2BIP8	Strong	Biomarker	[7]
Facial paresis, hereditary congenital, 3	DISAPJ2C	Strong	Autosomal recessive	[8]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
leukaemia	DISS7D1V	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Mobius syndrome	DIS9YXP5	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[2]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[10]
Ventricular septal defect	DISICO41	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	moderate	Biomarker	[12]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[12]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[12]
Ear malformation	DISVJGPS	moderate	Genetic Variation	[13]
Congenital hereditary facial paralysis-variable hearing loss syndrome	DIS9VUXS	Supportive	Autosomal recessive	[8]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-B1 (HOXB1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Homeobox protein Hox-B1 (HOXB1).	[16]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Homeobox protein Hox-B1 (HOXB1).	[17]
Dolutegravir	DMCZGRE	Approved	Dolutegravir increases the expression of Homeobox protein Hox-B1 (HOXB1).	[18]

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 affects the methylation of Homeobox protein Hox-B1 (HOXB1).	[19]

References

• [1] Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes.Blood. 1992 Jul 1;80(1):185-93.
• [2] Modulation of HOX2 gene expression following differentiation of neuronal cell lines.Differentiation. 1992 Sep;51(1):39-47. doi: 10.1111/j.1432-0436.1992.tb00678.x.
• [3] HOXB1 Is a Tumor Suppressor Gene Regulated by miR-3175 in Glioma.PLoS One. 2015 Nov 13;10(11):e0142387. doi: 10.1371/journal.pone.0142387. eCollection 2015.
• [4] Hsa-let-7g promotes osteosarcoma by reducing HOXB1 to activate NF-kB pathway.Biomed Pharmacother. 2019 Jan;109:2335-2341. doi: 10.1016/j.biopha.2018.11.026. Epub 2018 Nov 29.
• [5] Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1.Nat Genet. 1993 Jun;4(2):170-4. doi: 10.1038/ng0693-170.
• [6] HOXB homeobox gene expression in cervical carcinoma.Int J Gynecol Cancer. 2006 Jan-Feb;16(1):329-35. doi: 10.1111/j.1525-1438.2006.00350.x.
• [7] Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development.Development. 1999 Nov;126(22):5027-40. doi: 10.1242/dev.126.22.5027.
• [8] HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/- mice. Am J Hum Genet. 2012 Jul 13;91(1):171-9. doi: 10.1016/j.ajhg.2012.05.018. Epub 2012 Jul 5.
• [9] A new hereditary congenital facial palsy case supports arg5 in HOX-DNA binding domain as possible hot spot for mutations.Eur J Med Genet. 2015 Jun-Jul;58(6-7):358-63. doi: 10.1016/j.ejmg.2015.05.003. Epub 2015 May 23.
• [10] HOX gene expression in normal and neoplastic human kidney.Int J Cancer. 1992 Jul 30;51(6):892-7. doi: 10.1002/ijc.2910510610.
• [11] Analysis of HOXB1 gene in a cohort of patients with sporadic ventricular septal defect.Mol Biol Rep. 2018 Oct;45(5):1507-1513. doi: 10.1007/s11033-018-4212-x. Epub 2018 Jun 19.
• [12] Targeting the HOX/PBX dimer in breast cancer.Breast Cancer Res Treat. 2012 Nov;136(2):389-98. doi: 10.1007/s10549-012-2259-2. Epub 2012 Sep 30.
• [13] Homozygous HOXB1 loss-of-function mutation in a large family with hereditary congenital facial paresis.Am J Med Genet A. 2016 Jul;170(7):1813-9. doi: 10.1002/ajmg.a.37682. Epub 2016 May 4.
• [14] Characteristic patterns of HOX gene expression in different types of human leukemia.Int J Cancer. 1993 Jan 21;53(2):237-44. doi: 10.1002/ijc.2910530211.
• [15] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [18] Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity. Toxicol Sci. 2021 Nov 24;184(2):191-203. doi: 10.1093/toxsci/kfab112.
• [19] 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.