Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4BOYTM)

• DOT Name: Treacle protein (TCOF1)
• Synonyms: Treacher Collins syndrome protein
• Gene Name: TCOF1
• Related Disease:
  Treacher Collins syndrome 1
  Treacher-Collins syndrome
  Acute lymphocytic leukaemia
  Albinism
  Childhood acute lymphoblastic leukemia
  Classic Hodgkin lymphoma
  Cleft palate
  Common variable immunodeficiency
  Depression
  Epilepsy
  Esophageal adenocarcinoma
  Hepatocellular carcinoma
  Hypopigmentation of the skin
  Inflammatory bowel disease
  Isolated cleft palate
  Neoplasm
  Parkinson disease
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Progressive supranuclear palsy
  Ptosis
  T-cell acute lymphoblastic leukaemia
  Trichohepatoenteric syndrome
  Tuberculosis
  West syndrome
  High blood pressure
  Hirschsprung disease
  Intellectual disability
  Tuberous sclerosis
  Absence epilepsy
  Absence seizure
  Anxiety
  Anxiety disorder
  Epilepsy, idiopathic generalized
• UniProt ID: TCOF_HUMAN
• Pfam ID: PF03546
• Sequence:
  MAEARKRRELLPLIYHHLLRAGYVRAAREVKEQSGQKCFLAQPVTLLDIYTHWQQTSELG
  RKRKAEEDAALQAKKTRVSDPISTSESSEEEEEAEAETAKATPRLASTNSSVLGADLPSS
  MKEKAKAETEKAGKTGNSMPHPATGKTVANLLSGKSPRKSAEPSANTTLVSETEEEGSVP
  AFGAAAKPGMVSAGQADSSSEDTSSSSDETDVEGKPSVKPAQVKASSVSTKESPARKAAP
  APGKVGDVTPQVKGGALPPAKRAKKPEEESESSEEGSESEEEAPAGTRSQVKASEKILQV
  RAASAPAKGTPGKGATPAPPGKAGAVASQTKAGKPEEDSESSSEESSDSEEETPAAKALL
  QAKASGKTSQVGAASAPAKESPRKGAAPAPPGKTGPAVAKAQAGKREEDSQSSSEESDSE
  EEAPAQAKPSGKAPQVRAASAPAKESPRKGAAPAPPRKTGPAAAQVQVGKQEEDSRSSSE
  ESDSDREALAAMNAAQVKPLGKSPQVKPASTMGMGPLGKGAGPVPPGKVGPATPSAQVGK
  WEEDSESSSEESSDSSDGEVPTAVAPAQEKSLGNILQAKPTSSPAKGPPQKAGPVAVQVK
  AEKPMDNSESSEESSDSADSEEAPAAMTAAQAKPALKIPQTKACPKKTNTTASAKVAPVR
  VGTQAPRKAGTATSPAGSSPAVAGGTQRPAEDSSSSEESDSEEEKTGLAVTVGQAKSVGK
  GLQVKAASVPVKGSLGQGTAPVLPGKTGPTVTQVKAEKQEDSESSEEESDSEEAAASPAQ
  VKTSVKKTQAKANPAAARAPSAKGTISAPGKVVTAAAQAKQRSPSKVKPPVRNPQNSTVL
  ARGPASVPSVGKAVATAAQAQTGPEEDSGSSEEESDSEEEAETLAQVKPSGKTHQIRAAL
  APAKESPRKGAAPTPPGKTGPSAAQAGKQDDSGSSSEESDSDGEAPAAVTSAQVIKPPLI
  FVDPNRSPAGPAATPAQAQAASTPRKARASESTARSSSSESEDEDVIPATQCLTPGIRTN
  VVTMPTAHPRIAPKASMAGASSSKESSRISDGKKQEGPATQVSKKNPASLPLTQAALKVL
  AQKASEAQPPVARTQPSSGVDSAVGTLPATSPQSTSVQAKGTNKLRKPKLPEVQQATKAP
  ESSDDSEDSSDSSSGSEEDGEGPQGAKSAHTLGPTPSRTETLVEETAAESSEDDVVAPSQ
  SLLSGYMTPGLTPANSQASKATPKLDSSPSVSSTLAAKDDPDGKQEAKPQQAAGMLSPKT
  GGKEAASGTTPQKSRKPKKGAGNPQASTLALQSNITQCLLGQPWPLNEAQVQASVVKVLT
  ELLEQERKKVVDTTKESSRKGWESRKRKLSGDQPAARTPRSKKKKKLGAGEGGEASVSPE
  KTSTTSKGKAKRDKASGDVKEKKGKGSLGSQGAKDEPEEELQKGMGTVEGGDQSNPKSKK
  EKKKSDKRKKDKEKKEKKKKAKKASTKDSESPSQKKKKKKKKTAEQTV
• Function: Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification. Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Treacher Collins syndrome 1	DISCEP93	Definitive	Autosomal dominant	[1]
Treacher-Collins syndrome	DIS2GXZ1	Definitive	Autosomal dominant	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[3]
Albinism	DIS5D82I	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[3]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[5]
Cleft palate	DIS6G5TF	Strong	Biomarker	[6]
Common variable immunodeficiency	DISHE7JQ	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Epilepsy	DISBB28L	Strong	Genetic Variation	[9]
Esophageal adenocarcinoma	DISODWFP	Strong	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Hypopigmentation of the skin	DIS39YKC	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[12]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[10]
Parkinson disease	DISQVHKL	Strong	Biomarker	[13]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[14]
Progressive supranuclear palsy	DISO5KRQ	Strong	Biomarker	[15]
Ptosis	DISJZNIY	Strong	Biomarker	[16]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[17]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[18]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[19]
West syndrome	DISLIAU9	Strong	Biomarker	[20]
High blood pressure	DISY2OHH	moderate	Biomarker	[21]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[22]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[23]
Tuberous sclerosis	DISEMUGZ	moderate	Biomarker	[24]
Absence epilepsy	DISJPOUD	Limited	Biomarker	[25]
Absence seizure	DIS4709R	Limited	Biomarker	[25]
Anxiety	DISIJDBA	Limited	Biomarker	[26]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[26]
Epilepsy, idiopathic generalized	DISODZC9	Limited	Genetic Variation	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Treacle protein (TCOF1).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Treacle protein (TCOF1).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Treacle protein (TCOF1).	[29]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Treacle protein (TCOF1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Treacle protein (TCOF1).	[31]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Treacle protein (TCOF1).	[34]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Treacle protein (TCOF1).	[34]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Treacle protein (TCOF1).	[35]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Treacle protein (TCOF1).	[36]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Treacle protein (TCOF1).	[37]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Treacle protein (TCOF1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Treacle protein (TCOF1).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Treacle protein (TCOF1).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Treacle protein (TCOF1).	[32]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Treacle protein (TCOF1).	[33]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Treacle protein (TCOF1).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Treacle protein (TCOF1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Treacle protein (TCOF1).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Treacle protein (TCOF1).	[33]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Treacle protein (TCOF1).	[43]

References

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