Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSYIC3T)

• DOT Name: Hepatocyte nuclear factor 1-beta (HNF1B)
• Synonyms: HNF-1-beta; HNF-1B; Homeoprotein LFB3; Transcription factor 2; TCF-2; Variant hepatic nuclear factor 1; vHNF1
• Gene Name: HNF1B
• Related Disease:
  End-stage renal disease
  Familial primary hypomagnesemia
  Renal cysts and diabetes syndrome
  Breast carcinoma
  Carcinoma
  Cholestasis
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Congenital anomaly of kidney and urinary tract
  Cystic kidney disease
  Endometrial cancer
  Endometrium neoplasm
  Epithelial ovarian cancer
  Exocrine pancreatic insufficiency
  Fatty liver disease
  Gout
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung carcinoma
  Maturity-onset diabetes of the young
  Monogenic diabetes
  Nasopharyngeal carcinoma
  Obsolete diabetes mellitus, noninsulin-dependent
  Permanent neonatal diabetes mellitus
  Prostate neoplasm
  Testicular germ cell tumor
  Transient neonatal diabetes mellitus
  Autism
  Benign prostatic hyperplasia
  Endometrial carcinoma
  Familial prostate carcinoma
  Lung squamous cell carcinoma
  Ovarian cancer
  Medullary sponge kidney
  Renal dysplasia, bilateral
  Renal dysplasia, unilateral
  Renal hypomagnesemia 2
  Unilateral multicystic dysplastic kidney
  Intellectual disability
  Neonatal diabetes mellitus
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
• UniProt ID: HNF1B_HUMAN
• PDB ID: 2DA6; 2H8R; 5K9S
• Pfam ID: PF04814 ; PF04812
• Sequence:
  MVSKLTSLQQELLSALLSSGVTKEVLVQALEELLPSPNFGVKLETLPLSPGSGAEPDTKP
  VFHTLTNGHAKGRLSGDEGSEDGDDYDTPPILKELQALNTEEAAEQRAEVDRMLSEDPWR
  AAKMIKGYMQQHNIPQREVVDVTGLNQSHLSQHLNKGTPMKTQKRAALYTWYVRKQREIL
  RQFNQTVQSSGNMTDKSSQDQLLFLFPEFSQQSHGPGQSDDACSEPTNKKMRRNRFKWGP
  ASQQILYQAYDRQKNPSKEEREALVEECNRAECLQRGVSPSKAHGLGSNLVTEVRVYNWF
  ANRRKEEAFRQKLAMDAYSSNQTHSLNPLLSHGSPHHQPSSSPPNKLSGVRYSQQGNNEI
  TSSSTISHHGNSAMVTSQSVLQQVSPASLDPGHNLLSPDGKMISVSGGGLPPVSTLTNIH
  SLSHHNPQQSQNLIMTPLSGVMAIAQSLNTSQAQSVPVINSVAGSLAALQPVQFSQQLHS
  PHQQPLMQQSPGSHMAQQPFMAAVTQLQNSHMYAHKQEPPQYSHTSRFPSAMVVTDTSSI
  STLTNMSSSKQCPLQAW
• Function: Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Binds to the FPC element in the cAMP regulatory unit of the PLAU gene. Transcriptional activity is increased by coactivator PCBD1.
• KEGG Pathway: Maturity onset diabetes of the young (hsa04950)
• Reactome Pathway:
  Regulation of gene expression in early pancreatic precursor cells (R-HSA-210747)
  Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
End-stage renal disease	DISXA7GG	Definitive	Genetic Variation	[1]
Familial primary hypomagnesemia	DIS6TTKI	Definitive	Genetic Variation	[2]
Renal cysts and diabetes syndrome	DISNNWG2	Definitive	Autosomal dominant	[3]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Cholestasis	DISDJJWE	Strong	Genetic Variation	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[4]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[4]
Congenital anomaly of kidney and urinary tract	DIS84IVH	Strong	Genetic Variation	[8]
Cystic kidney disease	DISRT1LM	Strong	Genetic Variation	[9]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[10]
Endometrium neoplasm	DIS6OS2L	Strong	Genetic Variation	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Exocrine pancreatic insufficiency	DISCZYU2	Strong	Genetic Variation	[13]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[14]
Gout	DISHC0U7	Strong	Genetic Variation	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[4]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[4]
Maturity-onset diabetes of the young	DISG75M5	Strong	Genetic Variation	[17]
Monogenic diabetes	DISEB8Q0	Strong	Biomarker	[18]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[19]
Obsolete diabetes mellitus, noninsulin-dependent	DISS46MZ	Strong	Autosomal dominant	[20]
Permanent neonatal diabetes mellitus	DIS5AEXS	Strong	Autosomal dominant	[20]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[21]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[22]
Transient neonatal diabetes mellitus	DIST826V	Strong	Autosomal dominant	[20]
Autism	DISV4V1Z	moderate	Genetic Variation	[23]
Benign prostatic hyperplasia	DISI3CW2	moderate	Genetic Variation	[24]
Endometrial carcinoma	DISXR5CY	moderate	Genetic Variation	[25]
Familial prostate carcinoma	DISL9KNO	moderate	SusceptibilityMutation	[26]
Lung squamous cell carcinoma	DISXPIBD	moderate	Biomarker	[27]
Ovarian cancer	DISZJHAP	moderate	Genetic Variation	[28]
Medullary sponge kidney	DISA0949	Supportive	Autosomal dominant	[29]
Renal dysplasia, bilateral	DIS27M3V	Supportive	Autosomal dominant	[30]
Renal dysplasia, unilateral	DIS21V5M	Supportive	Autosomal dominant	[30]
Renal hypomagnesemia 2	DISAK1QC	Supportive	Autosomal dominant	[31]
Unilateral multicystic dysplastic kidney	DISUYQ0C	Supportive	Autosomal dominant	[32]
Intellectual disability	DISMBNXP	Disputed	Genetic Variation	[33]
Neonatal diabetes mellitus	DISFHF9K	Limited	Biomarker	[34]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[35]
Ovarian serous adenocarcinoma	DISSU72Z	Limited	Genetic Variation	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Hepatocyte nuclear factor 1-beta (HNF1B).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hepatocyte nuclear factor 1-beta (HNF1B).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[40]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[41]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[42]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[43]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[47]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[41]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Hepatocyte nuclear factor 1-beta (HNF1B).	[49]

References

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