Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBC960E)

• DOT Name: Zinc finger protein GLIS3 (GLIS3)
• Synonyms: GLI-similar 3; Zinc finger protein 515
• Gene Name: GLIS3
• Related Disease:
  Alzheimer disease
  Hyperglycemia
  Neonatal diabetes mellitus with congenital hypothyroidism
  Nervous system disease
  Acute megakaryoblastic leukemia
  Chronic obstructive pulmonary disease
  Clear cell renal carcinoma
  Congenital glaucoma
  Congenital hypothyroidism
  Cystic kidney disease
  Fibrolamellar liver cancer
  Hyperinsulinemia
  Knee osteoarthritis
  Leber hereditary optic neuropathy
  MELAS syndrome
  Multiple sclerosis
  Narcolepsy
  Non-insulin dependent diabetes
  Osteoarthritis
  Renal cell carcinoma
  Sensorineural hearing loss disorder
  Thyroid gland papillary carcinoma
  Thyroid tumor
  Type-1/2 diabetes
  Angle-closure glaucoma
  Nephronophthisis
  Monogenic diabetes
  Advanced cancer
  Autoimmune disease
  Fibrosarcoma
  Goiter
  Hypothyroidism
  Melanoma
  Neonatal diabetes mellitus
  Polycystic kidney disease
  Primary angle-closure glaucoma
  Schizophrenia
  Tourette syndrome
  Type-1 diabetes
• UniProt ID: GLIS3_HUMAN
• Pfam ID: PF00096
• Sequence:
  MMVQRLGLISPPASQVSTACNQISPSLQRAMNAANLNIPPSDTRSLISRESLASTTLSLT
  ESQSASSMKQEWSQGYRALPSLSNHGSQNGLDLGDLLSLPPGTSMSSNSVSNSLPSYLFG
  TESSHSPYPSPRHSSTRSHSARSKKRALSLSPLSDGIGIDFNTIIRTSPTSLVAYINGSR
  ASPANLSPQPEVYGHFLGVRGSCIPQPRPVPGSQKGVLVAPGGLALPAYGEDGALEHERM
  QQLEHGGLQPGLVNHMVVQHGLPGPDSQSAGLFKTERLEEFPGSTVDLPPAPPLPPLPPP
  PGPPPPYHAHAHLHHPELGPHAQQLALPQATLDDDGEMDGIGGKHCCRWIDCSALYDQQE
  ELVRHIEKVHIDQRKGEDFTCFWAGCPRRYKPFNARYKLLIHMRVHSGEKPNKCTFEGCE
  KAFSRLENLKIHLRSHTGEKPYLCQHPGCQKAFSNSSDRAKHQRTHLDTKPYACQIPGCT
  KRYTDPSSLRKHVKAHSSKEQQARKKLRSSTELHPDLLTDCLTVQSLQPATSPRDAAAEG
  TVGRSPGPGPDLYSAPIFSSNYSSRSGTAAGAVPPPHPVSHPSPGHNVQGSPHNPSSQLP
  PLTAVDAGAERFAPSAPSPHHISPRRVPAPSSILQRTQPPYTQQPSGSHLKSYQPETNSS
  FQPNGIHVHGFYGQLQKFCPPHYPDSQRIVPPVSSCSVVPSFEDCLVPTSMGQASFDVFH
  RAFSTHSGITVYDLPSSSSSLFGESLRSGAEDATFLQISTVDRCPSQLSSVYTEG
• Function: Acts both as a repressor and an activator of transcription. Binds to the consensus sequence 5'-GACCACCCAC-3'.
• Tissue Specificity: In the adult, expressed at high levels in the kidney and at lower levels in the brain, skeletal muscle, pancreas, liver, lung, thymus and ovary.

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Definitive	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Definitive	Biomarker	[2]
Neonatal diabetes mellitus with congenital hypothyroidism	DISA2P6G	Definitive	Autosomal recessive	[3]
Nervous system disease	DISJ7GGT	Definitive	Genetic Variation	[4]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Genetic Variation	[5]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[7]
Congenital glaucoma	DISHN3GO	Strong	Biomarker	[8]
Congenital hypothyroidism	DISL5XVU	Strong	Genetic Variation	[9]
Cystic kidney disease	DISRT1LM	Strong	Biomarker	[10]
Fibrolamellar liver cancer	DISUDA2P	Strong	Biomarker	[5]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[1]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[11]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Genetic Variation	[12]
MELAS syndrome	DIS81Z3S	Strong	Genetic Variation	[13]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[14]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[16]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[7]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[8]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[17]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[19]
Angle-closure glaucoma	DISZ95KY	moderate	Genetic Variation	[20]
Nephronophthisis	DISXU4HY	moderate	Genetic Variation	[21]
Monogenic diabetes	DISEB8Q0	Disputed	Biomarker	[22]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[23]
Autoimmune disease	DISORMTM	Limited	Genetic Variation	[24]
Fibrosarcoma	DISWX7MU	Limited	Biomarker	[25]
Goiter	DISLCGI6	Limited	Biomarker	[26]
Hypothyroidism	DISR0H6D	Limited	Biomarker	[26]
Melanoma	DIS1RRCY	Limited	Biomarker	[27]
Neonatal diabetes mellitus	DISFHF9K	Limited	Genetic Variation	[28]
Polycystic kidney disease	DISWS3UY	Limited	Biomarker	[29]
Primary angle-closure glaucoma	DISX8UKZ	Limited	Genetic Variation	[20]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[30]
Tourette syndrome	DISX9D54	Limited	Unknown	[31]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[25]

3 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 Zinc finger protein GLIS3 (GLIS3).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc finger protein GLIS3 (GLIS3).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Zinc finger protein GLIS3 (GLIS3).	[45]

14 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 Zinc finger protein GLIS3 (GLIS3).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Zinc finger protein GLIS3 (GLIS3).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Zinc finger protein GLIS3 (GLIS3).	[38]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Zinc finger protein GLIS3 (GLIS3).	[39]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[40]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[41]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Zinc finger protein GLIS3 (GLIS3).	[42]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[40]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Zinc finger protein GLIS3 (GLIS3).	[43]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Zinc finger protein GLIS3 (GLIS3).	[46]

References

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