Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMSOJ7D)

• DOT Name: Homeobox protein Hox-A1 (HOXA1)
• Synonyms: Homeobox protein Hox-1F
• Gene Name: HOXA1
• Related Disease:
  Acute myelogenous leukaemia
  Human HOXA1 syndromes
  Syndromic intellectual disability
  Arteriosclerosis
  Atherosclerosis
  Bladder cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Chromosomal disorder
  Congenital heart disease
  Congenital nervous system disorder
  Epithelial ovarian cancer
  Esophageal cancer
  Gastric cancer
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Mobius syndrome
  Neoplasm
  Neoplasm of esophagus
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Promyelocytic leukaemia
  Small-cell lung cancer
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Chronic obstructive pulmonary disease
  Duane retraction syndrome
  Plasma cell myeloma
  Bosley-Salih-Alorainy syndrome
  Melanoma
  Adenocarcinoma
  Advanced cancer
  Autism spectrum disorder
  Breast cancer
  Cognitive impairment
  Glioblastoma multiforme
  Intellectual disability
  Mesothelioma
  Non-small-cell lung cancer
  Osteoarthritis
  Prostate cancer
  Prostate carcinoma
• UniProt ID: HXA1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MDNARMNSFLEYPILSSGDSGTCSARAYPSDHRITTFQSCAVSANSCGGDDRFLVGRGVQ
  IGSPHHHHHHHHHHPQPATYQTSGNLGVSYSHSSCGPSYGSQNFSAPYSPYALNQEADVS
  GGYPQCAPAVYSGNLSSPMVQHHHHHQGYAGGAVGSPQYIHHSYGQEHQSLALATYNNSL
  SPLHASHQEACRSPASETSSPAQTFDWMKVKRNPPKTGKVGEYGYLGQPNAVRTNFTTKQ
  LTELEKEFHFNKYLTRARRVEIAASLQLNETQVKIWFQNRRMKQKKREKEGLLPISPATP
  PGNDEKAEESSEKSSSSPCVPSPGSSTSDTLTTSH
• Function: Sequence-specific transcription factor. Regulates multiple developmental processes including brainstem, inner and outer ear, abducens nerve and cardiovascular development and morphogenesis as well as cognition and behavior. Also part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. Seems to act in the maintenance and/or generation of hindbrain segments. Activates transcription in the presence of PBX1A and PKNOX1.
• 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

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Human HOXA1 syndromes	DISISIYH	Definitive	Autosomal recessive	[2]
Syndromic intellectual disability	DISH7SDF	Definitive	Autosomal recessive	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[10]
Congenital heart disease	DISQBA23	Strong	Genetic Variation	[11]
Congenital nervous system disorder	DIS2BIP8	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Mobius syndrome	DIS9YXP5	Strong	Genetic Variation	[18]
Neoplasm	DISZKGEW	Strong	Altered Expression	[19]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[13]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[13]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[20]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[21]
Small-cell lung cancer	DISK3LZD	Strong	Posttranslational Modification	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[23]
Stomach cancer	DISKIJSX	Strong	Biomarker	[14]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[24]
Duane retraction syndrome	DISOEBK2	moderate	Biomarker	[25]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[26]
Bosley-Salih-Alorainy syndrome	DISFEFR1	Supportive	Autosomal recessive	[27]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[28]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[29]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[6]
Autism spectrum disorder	DISXK8NV	Limited	Genetic Variation	[30]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[6]
Cognitive impairment	DISH2ERD	Limited	Genetic Variation	[31]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[32]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[33]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[34]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[35]
Osteoarthritis	DIS05URM	Limited	Biomarker	[36]
Prostate cancer	DISF190Y	Limited	Biomarker	[37]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[37]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cyclophosphamide	DM4O2Z7	Approved	Homeobox protein Hox-A1 (HOXA1) affects the response to substance of Cyclophosphamide.	[51]
Camptothecin	DM6CHNJ	Phase 3	Homeobox protein Hox-A1 (HOXA1) decreases the response to substance of Camptothecin.	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Homeobox protein Hox-A1 (HOXA1).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-A1 (HOXA1).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Homeobox protein Hox-A1 (HOXA1).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Homeobox protein Hox-A1 (HOXA1).	[41]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-A1 (HOXA1).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Homeobox protein Hox-A1 (HOXA1).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Homeobox protein Hox-A1 (HOXA1).	[44]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Homeobox protein Hox-A1 (HOXA1).	[45]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Homeobox protein Hox-A1 (HOXA1).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Homeobox protein Hox-A1 (HOXA1).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Homeobox protein Hox-A1 (HOXA1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Homeobox protein Hox-A1 (HOXA1).	[50]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Homeobox protein Hox-A1 (HOXA1).	[45]

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-A1 (HOXA1).	[48]

References

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• [12] 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.
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• [25] The genetic basis of incomitant strabismus: consolidation of the current knowledge of the genetic foundations of disease.Semin Ophthalmol. 2013 Sep-Nov;28(5-6):427-37. doi: 10.3109/08820538.2013.825288.
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• [31] Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to the DURS2 genetic locus.Invest Ophthalmol Vis Sci. 2007 Jan;48(1):189-93. doi: 10.1167/iovs.06-0631.
• [32] Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme.J Exp Clin Cancer Res. 2018 Oct 30;37(1):265. doi: 10.1186/s13046-018-0941-x.
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