Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8DXI40)

• DOT Name: PHD finger protein 6 (PHF6)
• Synonyms: PHD-like zinc finger protein
• Gene Name: PHF6
• Related Disease:
  Borjeson-Forssman-Lehmann syndrome
  Epilepsy
  Acute monocytic leukemia
  Acute undifferentiated leukemia
  Adult acute monocytic leukemia
  Adult glioblastoma
  Alzheimer disease
  Amyloidosis
  Coffin-Siris syndrome
  Colorectal carcinoma
  Glioblastoma multiforme
  Haematological malignancy
  leukaemia
  Leukemia
  Marinesco-Sjogren syndrome
  Myelodysplastic syndrome
  Neoplasm
  Neoplasm of esophagus
  Non-insulin dependent diabetes
  Obesity
  T-cell lymphoma
  X-linked intellectual disability
  Hepatocellular carcinoma
  Intellectual disability
  Acute myelogenous leukaemia
  Advanced cancer
  Myeloid neoplasm
  Neuroblastoma
  Neurodevelopmental disorder
  Tauopathy
• UniProt ID: PHF6_HUMAN
• PDB ID: 4NN2; 4R7A
• Pfam ID: PF13771
• Sequence:
  MSSSVEQKKGPTRQRKCGFCKSNRDKECGQLLISENQKVAAHHKCMLFSSALVSSHSDNE
  SLGGFSIEDVQKEIKRGTKLMCSLCHCPGATIGCDVKTCHRTYHYHCALHDKAQIREKPS
  QGIYMVYCRKHKKTAHNSEADLEESFNEHELEPSSPKSKKKSRKGRPRKTNFKGLSEDTR
  STSSHGTDEMESSSYRDRSPHRSSPSDTRPKCGFCHVGEEENEARGKLHIFNAKKAAAHY
  KCMLFSSGTVQLTTTSRAEFGDFDIKTVLQEIKRGKRMKCTLCSQPGATIGCEIKACVKT
  YHYHCGVQDKAKYIENMSRGIYKLYCKNHSGNDERDEEDEERESKSRGKVEIDQQQLTQQ
  QLNGN
• Function: Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Borjeson-Forssman-Lehmann syndrome	DISJ5QNF	Definitive	X-linked	[1]
Epilepsy	DISBB28L	Definitive	Biomarker	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[3]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[3]
Adult acute monocytic leukemia	DISG6BLX	Strong	Genetic Variation	[3]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Coffin-Siris syndrome	DIS8L03H	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[8]
leukaemia	DISS7D1V	Strong	Biomarker	[8]
Leukemia	DISNAKFL	Strong	Biomarker	[8]
Marinesco-Sjogren syndrome	DISKEU0B	Strong	Genetic Variation	[9]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Obesity	DIS47Y1K	Strong	Genetic Variation	[12]
T-cell lymphoma	DISSXRTQ	Strong	Altered Expression	[13]
X-linked intellectual disability	DISYJBY3	Strong	Genetic Variation	[14]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[15]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[16]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[17]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[7]
Myeloid neoplasm	DIS2YOWO	Limited	Genetic Variation	[18]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[19]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[16]
Tauopathy	DISY2IPA	Limited	Biomarker	[20]

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 PHD finger protein 6 (PHF6).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PHD finger protein 6 (PHF6).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PHD finger protein 6 (PHF6).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PHD finger protein 6 (PHF6).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PHD finger protein 6 (PHF6).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PHD finger protein 6 (PHF6).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of PHD finger protein 6 (PHF6).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of PHD finger protein 6 (PHF6).	[28]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of PHD finger protein 6 (PHF6).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of PHD finger protein 6 (PHF6).	[30]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of PHD finger protein 6 (PHF6).	[31]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PHD finger protein 6 (PHF6).	[32]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of PHD finger protein 6 (PHF6).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PHD finger protein 6 (PHF6).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of PHD finger protein 6 (PHF6).	[37]

2 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 affects the methylation of PHD finger protein 6 (PHF6).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PHD finger protein 6 (PHF6).	[35]

References

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• [20] Disclosing the Mechanism of Spontaneous Aggregation and Template-Induced Misfolding of the Key Hexapeptide (PHF6) of Tau Protein Based on Molecular Dynamics Simulation.ACS Chem Neurosci. 2019 Dec 18;10(12):4810-4823. doi: 10.1021/acschemneuro.9b00488. Epub 2019 Nov 12.
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• [23] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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