Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9AJQY)

• DOT Name: Zinc finger protein PLAG1 (PLAG1)
• Synonyms: Pleiomorphic adenoma gene 1 protein
• Gene Name: PLAG1
• Related Disease:
  Metastatic malignant neoplasm
  Adenoma
  Alzheimer disease
  Anxiety disorder
  Benign neoplasm
  Benign prostatic hyperplasia
  Breast neoplasm
  Chromosomal disorder
  Epithelial ovarian cancer
  Familial prostate carcinoma
  Fetal growth restriction
  Helicoid peripapillary chorioretinal degeneration
  Hereditary chronic pancreatitis
  Huntington disease
  Leiomyoma
  Lung cancer
  Non-insulin dependent diabetes
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate adenocarcinoma
  Prostate disease
  Prostatitis
  Retinitis pigmentosa
  Silver-Russell syndrome
  Silver-russell syndrome 4
  Small lymphocytic lymphoma
  Syndromic X-linked intellectual disability Snyder type
  Type-1/2 diabetes
  Uterine fibroids
  Adenocarcinoma
  Cardiovascular disease
  Cowden disease
  Early-onset anterior polar cataract
  Hepatocellular carcinoma
  High blood pressure
  Squamous cell carcinoma
  Acute myelogenous leukaemia
  Lung carcinoma
  Melanoma
  Metastatic prostate carcinoma
  Pachyonychia congenita 3
• UniProt ID: PLAG1_HUMAN
• Pfam ID: PF00096 ; PF13912
• Sequence:
  MATVIPGDLSEVRDTQKVPSGKRKRGETKPRKNFPCQLCDKAFNSVEKLKVHSYSHTGER
  PYKCIQQDCTKAFVSKYKLQRHMATHSPEKTHKCNYCEKMFHRKDHLKNHLHTHDPNKET
  FKCEECGKNYNTKLGFKRHLALHAATSGDLTCKVCLQTFESTGVLLEHLKSHAGKSSGGV
  KEKKHQCEHCDRRFYTRKDVRRHMVVHTGRKDFLCQYCAQRFGRKDHLTRHMKKSHNQEL
  LKVKTEPVDFLDPFTCNVSVPIKDELLPVMSLPSSELLSKPFTNTLQLNLYNTPFQSMQS
  SGSAHQMITTLPLGMTCPIDMDTVHPSHHLSFKYPFSSTSYAISIPEKEQPLKGEIESYL
  MELQGGVPSSSQDSQASSSSKLGLDPQIGSLDDGAGDLSLSKSSISISDPLNTPALDFSQ
  LFNFIPLNGPPYNPLSVGSLGMSYSQEEAHSSVSQLPPQTQDLQDPANTIGLGSLHSLSA
  AFTSSLSTSTTLPRFHQAFQ
• Function: Transcription factor whose activation results in up-regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Overexpression is associated with up-regulation of IGFII, is frequently observed in hepatoblastoma, common primary liver tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important for myeloid leukemia.
• Tissue Specificity: Expressed in fetal tissues such as lung, liver and kidney. Not detected or weak detection in normal adult tissues, but highly expressed in salivary gland with benign or malignant pleiomorphic adenomas with or without 8q12 aberrations, with preferential occurrence in benign tumors.

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[4]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[5]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[9]
Familial prostate carcinoma	DISL9KNO	Strong	Genetic Variation	[10]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[11]
Helicoid peripapillary chorioretinal degeneration	DISFSS5N	Strong	Genetic Variation	[12]
Hereditary chronic pancreatitis	DISF0J1Q	Strong	Genetic Variation	[10]
Huntington disease	DISQPLA4	Strong	Biomarker	[13]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[14]
Lung cancer	DISCM4YA	Strong	Biomarker	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[9]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[9]
Prostate adenocarcinoma	DISBZYU8	Strong	Genetic Variation	[18]
Prostate disease	DISFVG19	Strong	Biomarker	[19]
Prostatitis	DISL8OGN	Strong	Biomarker	[20]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[21]
Silver-Russell syndrome	DISSVJ1D	Strong	Biomarker	[11]
Silver-russell syndrome 4	DIS24AA4	Strong	Autosomal dominant	[22]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[23]
Syndromic X-linked intellectual disability Snyder type	DISN836E	Strong	Biomarker	[11]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[17]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[14]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[24]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[25]
Cowden disease	DISMYKCE	moderate	Biomarker	[26]
Early-onset anterior polar cataract	DISTOPIY	moderate	Biomarker	[27]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[28]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[29]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[30]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Biomarker	[31]
Lung carcinoma	DISTR26C	Limited	Biomarker	[15]
Melanoma	DIS1RRCY	Limited	Altered Expression	[32]
Metastatic prostate carcinoma	DISVBEZ9	Limited	Altered Expression	[33]
Pachyonychia congenita 3	DISZLC6C	Limited	Biomarker	[34]

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 Zinc finger protein PLAG1 (PLAG1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Zinc finger protein PLAG1 (PLAG1).	[44]

11 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 PLAG1 (PLAG1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Zinc finger protein PLAG1 (PLAG1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger protein PLAG1 (PLAG1).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Zinc finger protein PLAG1 (PLAG1).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Zinc finger protein PLAG1 (PLAG1).	[40]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Zinc finger protein PLAG1 (PLAG1).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc finger protein PLAG1 (PLAG1).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Zinc finger protein PLAG1 (PLAG1).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Zinc finger protein PLAG1 (PLAG1).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger protein PLAG1 (PLAG1).	[45]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Zinc finger protein PLAG1 (PLAG1).	[46]

References

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