Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOUUV1X)

• DOT Name: Zinc finger protein GLIS2 (GLIS2)
• Synonyms: GLI-similar 2; Neuronal Krueppel-like protein
• Gene Name: GLIS2
• Related Disease:
  Acute megakaryoblastic leukemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Autosomal dominant polycystic kidney disease
  B-cell lymphoma
  B-cell neoplasm
  Bardet biedl syndrome
  Caroli disease
  Childhood acute megakaryoblastic leukemia
  Ciliopathy
  Fibrolamellar liver cancer
  Gastrointestinal stromal tumour
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hepatosplenic T-cell lymphoma
  Kidney failure
  leukaemia
  Leukemia
  Lymphoma
  Mantle cell lymphoma
  Myelodysplastic syndrome
  Nephronophthisis 7
  Nephropathy
  Normal pressure hydrocephalus
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Renal fibrosis
  T-cell lymphoma
  Neonatal diabetes mellitus
  Nephronophthisis
  Nephronophthisis 1
  Adult lymphoma
  Chronic kidney disease
  Classic Hodgkin lymphoma
  Gastric cancer
  Lymphoid leukemia
  Neoplasm
  Pediatric lymphoma
  Stomach cancer
  T-cell acute lymphoblastic leukaemia
  T-cell leukaemia
• UniProt ID: GLIS2_HUMAN
• Pfam ID: PF00096
• Sequence:
  MHSLDEPLDLKLSITKLRAAREKRERTLGVVRPRALHRELGLVDDSPTPGSPGSPPSGFL
  LNSKFPEKVEGRFSAAPLVDLSLSPPSGLDSPNGSSSLSPERQGNGDLPPVPSASDFQPL
  RYLDGVPSSFQFFLPLGSGGALHLPASSFLTPPKDKCLSPDLPLPKQLVCRWAKCNQLFE
  LLQDLVDHVNDYHVKPEKDAGYCCHWEGCARHGRGFNARYKMLIHIRTHTNEKPHRCPTC
  SKSFSRLENLKIHNRSHTGEKPYVCPYEGCNKRYSNSSDRFKHTRTHYVDKPYYCKMPGC
  HKRYTDPSSLRKHIKAHGHFVSHEQQELLQLRPPPKPPLPAPDGGPYVSGAQIIIPNPAA
  LFGGPGLPGLPLPLAPGPLDLSALACGNGGGSGGGGGMGPGLPGPVLPLNLAKNPLLPSP
  FGAGGLGLPVVSLLAGAAGGKAEGEKGRGSVPTRALGMEGHKTPLERTESSCSRPSPDGL
  PLLPGTVLDLSTGVNSAASSPEALAPGWVVIPPGSVLLKPAVVN
• Function: Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context. Acts as a repressor of the Hedgehog signaling pathway. Represses the Hedgehog-dependent expression of Wnt4. Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition. Represses transcriptional activation mediated by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation.
• Tissue Specificity: Expressed at high levels in kidney and at low levels in heart, lung and placenta. Expressed in colon.

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute megakaryoblastic leukemia	DIS0JX3M	Definitive	Biomarker	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Autosomal dominant polycystic kidney disease	DISBHWUI	Strong	Biomarker	[6]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Biomarker	[8]
Bardet biedl syndrome	DISTBNZW	Strong	Biomarker	[9]
Caroli disease	DISXQYMX	Strong	Genetic Variation	[10]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Biomarker	[11]
Ciliopathy	DIS10G4I	Strong	Altered Expression	[9]
Fibrolamellar liver cancer	DISUDA2P	Strong	Genetic Variation	[5]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Hepatosplenic T-cell lymphoma	DIS7KMY9	Strong	Biomarker	[14]
Kidney failure	DISOVQ9P	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Altered Expression	[13]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Lymphoma	DISN6V4S	Strong	Biomarker	[16]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[17]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[18]
Nephronophthisis 7	DIS6LSO8	Strong	Autosomal recessive	[19]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[20]
Normal pressure hydrocephalus	DISOEFO9	Strong	Genetic Variation	[21]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[14]
Renal fibrosis	DISMHI3I	Strong	Genetic Variation	[22]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[14]
Neonatal diabetes mellitus	DISFHF9K	moderate	Genetic Variation	[23]
Nephronophthisis	DISXU4HY	moderate	Biomarker	[24]
Nephronophthisis 1	DIS7QNQ3	Supportive	Autosomal recessive	[19]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[25]
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[22]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Altered Expression	[26]
Gastric cancer	DISXGOUK	Limited	Biomarker	[27]
Lymphoid leukemia	DIS65TYQ	Limited	Biomarker	[25]
Neoplasm	DISZKGEW	Limited	Biomarker	[28]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[25]
Stomach cancer	DISKIJSX	Limited	Biomarker	[27]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Genetic Variation	[29]
T-cell leukaemia	DISJ6YIF	Limited	Biomarker	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Zinc finger protein GLIS2 (GLIS2).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Zinc finger protein GLIS2 (GLIS2).	[35]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Zinc finger protein GLIS2 (GLIS2).	[39]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Zinc finger protein GLIS2 (GLIS2).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Zinc finger protein GLIS2 (GLIS2).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger protein GLIS2 (GLIS2).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Zinc finger protein GLIS2 (GLIS2).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Zinc finger protein GLIS2 (GLIS2).	[34]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Zinc finger protein GLIS2 (GLIS2).	[36]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Zinc finger protein GLIS2 (GLIS2).	[37]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Zinc finger protein GLIS2 (GLIS2).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Zinc finger protein GLIS2 (GLIS2).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Zinc finger protein GLIS2 (GLIS2).	[41]

References

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• [20] SUMOylation Blocks the Ubiquitin-Mediated Degradation of the Nephronophthisis Gene Product Glis2/NPHP7.PLoS One. 2015 Jun 17;10(6):e0130275. doi: 10.1371/journal.pone.0130275. eCollection 2015.
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