Details of Drug Off-Target (DOT)

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

• DOT Name: Hematopoietically-expressed homeobox protein HHEX (HHEX)
• Synonyms: Homeobox protein HEX; Homeobox protein PRH; Proline-rich homeodomain protein
• Gene Name: HHEX
• Related Disease:
  Diabetic retinopathy
  Epithelial neoplasm
  Neural tube defect
  Thyroid tumor
  Undifferentiated carcinoma
  Acute myelogenous leukaemia
  Acute undifferentiated leukemia
  Advanced cancer
  Alzheimer disease
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cholangiocarcinoma
  Cholelithiasis
  Congenital contractural arachnodactyly
  Congenital hypothyroidism
  Dementia
  Dilated cardiomyopathy 1A
  Ductal breast carcinoma in situ
  Fatty liver disease
  Glucose-galactose malabsorption
  GM2 gangliosidosis
  Inflammatory breast cancer
  Mycosis fungoides
  Myocardial infarction
  Neoplasm
  Obesity
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Pulmonary disease
  Sezary syndrome
  T-cell acute lymphoblastic leukaemia
  Tay-sachs disease
  Alcohol dependence
  Carcinoma
  Coronary heart disease
  Hepatocellular carcinoma
  Lysosomal storage disease
  Sandhoff disease
• UniProt ID: HHEX_HUMAN
• PDB ID: 2E1O
• Pfam ID: PF00046
• Sequence:
  MQYPHPGPAAGAVGVPLYAPTPLLQPAHPTPFYIEDILGRGPAAPTPAPTLPSPNSSFTS
  LVSPYRTPVYEPTPIHPAFSHHSAAALAAAYGPGGFGGPLYPFPRTVNDYTHALLRHDPL
  GKPLLWSPFLQRPLHKRKGGQVRFSNDQTIELEKKFETQKYLSPPERKRLAKMLQLSERQ
  VKTWFQNRRAKWRRLKQENPQSNKKEELESLDSSCDQRQDLPSEQNKGASLDSSQCSPSP
  ASQEDLESEISEDSDQEVDIEGDKSYFNAG
• Function: Recognizes the DNA sequence 5'-ATTAA-3'. Transcriptional repressor. Activator of WNT-mediated transcription in conjunction with CTNNB1. Establishes anterior identity at two levels; acts early to enhance canonical WNT-signaling by repressing expression of TLE4, and acts later to inhibit NODAL-signaling by directly targeting NODAL. Inhibits EIF4E-mediated mRNA nuclear export. May play a role in hematopoietic differentiation.
• Tissue Specificity: Liver and promyelocytic leukemia cell line HL-60.
• KEGG Pathway:
  Maturity onset diabetes of the young (hsa04950)
  Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Genetic Variation	[1]
Epithelial neoplasm	DIS0T594	Definitive	Biomarker	[2]
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[3]
Thyroid tumor	DISLVKMD	Definitive	Altered Expression	[2]
Undifferentiated carcinoma	DISIAZST	Definitive	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[9]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Genetic Variation	[10]
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[11]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[12]
Congenital hypothyroidism	DISL5XVU	Strong	Genetic Variation	[13]
Dementia	DISXL1WY	Strong	Biomarker	[7]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[14]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Biomarker	[6]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[15]
Glucose-galactose malabsorption	DISBFXNW	Strong	Biomarker	[16]
GM2 gangliosidosis	DISPT716	Strong	Genetic Variation	[17]
Inflammatory breast cancer	DIS3QRWA	Strong	Biomarker	[6]
Mycosis fungoides	DIS62RB8	Strong	Biomarker	[18]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[21]
Prostate cancer	DISF190Y	Strong	Altered Expression	[8]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[8]
Pulmonary disease	DIS6060I	Strong	Biomarker	[22]
Sezary syndrome	DISFMTC7	Strong	Biomarker	[18]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[23]
Tay-sachs disease	DISWG5B4	Strong	Genetic Variation	[24]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[25]
Carcinoma	DISH9F1N	moderate	Altered Expression	[26]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[27]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[28]
Lysosomal storage disease	DIS6QM6U	Limited	Genetic Variation	[29]
Sandhoff disease	DISELKA4	Limited	Genetic Variation	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Hematopoietically-expressed homeobox protein HHEX (HHEX) affects the response to substance of Cisplatin.	[45]
Mitomycin	DMH0ZJE	Approved	Hematopoietically-expressed homeobox protein HHEX (HHEX) affects the response to substance of Mitomycin.	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[30]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[33]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[34]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[35]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[36]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[37]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[38]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[39]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[43]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Hematopoietically-expressed homeobox protein HHEX (HHEX).	[44]

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 Hematopoietically-expressed homeobox protein HHEX (HHEX).	[40]

References

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