Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRL219S)

• DOT Name: General transcription factor IIH subunit 5 (GTF2H5)
• Synonyms: General transcription factor IIH polypeptide 5; TFB5 ortholog; TFIIH basal transcription factor complex TTD-A subunit; TFIIH subunit p8
• Gene Name: GTF2H5
• Related Disease:
  Advanced cancer
  Neoplasm
  Trichothiodystrophy 1, photosensitive
  Xeroderma pigmentosum group B
  Xeroderma pigmentosum group G
  Ablepharon macrostomia syndrome
  Cockayne syndrome type 1
  Colorectal carcinoma
  Familial pancreatic carcinoma
  Hutchinson-Gilford progeria syndrome
  Insomnia
  Melanoma
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Rift valley fever
  Skin disease
  Spinal muscular atrophy
  Spinal muscular atrophy, type 1
  Trichothiodystrophy 3, photosensitive
  Xeroderma pigmentosum group A
  Xeroderma pigmentosum group D
  Xeroderma pigmentosum-Cockayne syndrome complex
  Head-neck squamous cell carcinoma
  Periodontitis
  Skin cancer
  Trichothiodystrophy
  Cowden disease
  Cockayne syndrome
  Type-1/2 diabetes
• UniProt ID: TF2H5_HUMAN
• PDB ID: 1YDL ; 2JNJ ; 5IVW ; 5IY6 ; 5IY7 ; 5IY8 ; 5IY9 ; 5OF4 ; 6NMI ; 6O9L ; 6O9M ; 6RO4 ; 7AD8 ; 7EGB ; 7EGC ; 7ENA ; 7ENC ; 7LBM ; 7NVR ; 7NVV ; 7NVW ; 7NVX ; 7NVY ; 7NVZ ; 7NW0 ; 8BVW ; 8BYQ ; 8EBS ; 8EBT ; 8EBU ; 8EBV ; 8EBW ; 8EBX ; 8EBY ; 8GXQ ; 8GXS ; 8WAK ; 8WAL ; 8WAN ; 8WAO ; 8WAP ; 8WAQ ; 8WAR ; 8WAS
• Pfam ID: PF06331
• Sequence:
  MVNVLKGVLIECDPAMKQFLLYLDESNALGKKFIIQDIDDTHVFVIAELVNVLQERVGEL
  MDQNAFSLTQK
• Function: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. Necessary for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Nucleotide excision repair (hsa03420)
• Reactome Pathway:
  Formation of the Early Elongation Complex (R-HSA-113418)
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of the HIV-1 Early Elongation Complex (R-HSA-167158)
  RNA Pol II CTD phosphorylation and interaction with CE during HIV infection (R-HSA-167160)
  HIV Transcription Initiation (R-HSA-167161)
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Dual Incision in GG-NER (R-HSA-5696400)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)
  Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  mRNA Capping (R-HSA-72086)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  RNA Polymerase I Promoter Escape (R-HSA-73772)
  RNA Polymerase II Promoter Escape (R-HSA-73776)
  RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779)
  RNA Polymerase I Transcription Termination (R-HSA-73863)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  RNA Pol II CTD phosphorylation and interaction with CE (R-HSA-77075)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Trichothiodystrophy 1, photosensitive	DISK51NL	Definitive	Autosomal recessive	[3]
Xeroderma pigmentosum group B	DIS1EFEV	Definitive	Biomarker	[4]
Xeroderma pigmentosum group G	DIS4PV33	Definitive	Biomarker	[5]
Ablepharon macrostomia syndrome	DIS1P3YX	Strong	Biomarker	[6]
Cockayne syndrome type 1	DIS9JFVY	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Familial pancreatic carcinoma	DIS1XROR	Strong	Biomarker	[9]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Genetic Variation	[1]
Insomnia	DIS0AFR7	Strong	Biomarker	[10]
Melanoma	DIS1RRCY	Strong	Altered Expression	[11]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Prostate cancer	DISF190Y	Strong	Altered Expression	[13]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[13]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[14]
Rift valley fever	DISG6CM2	Strong	Altered Expression	[15]
Skin disease	DISDW8R6	Strong	Altered Expression	[16]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[17]
Spinal muscular atrophy, type 1	DISYCWUG	Strong	Altered Expression	[17]
Trichothiodystrophy 3, photosensitive	DIS2MS40	Strong	Autosomal recessive	[18]
Xeroderma pigmentosum group A	DIS38HWC	Strong	Genetic Variation	[19]
Xeroderma pigmentosum group D	DISFFE93	Strong	Biomarker	[20]
Xeroderma pigmentosum-Cockayne syndrome complex	DISJ0QRY	Strong	Genetic Variation	[21]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[22]
Periodontitis	DISI9JOI	moderate	Genetic Variation	[23]
Skin cancer	DISTM18U	moderate	Altered Expression	[24]
Trichothiodystrophy	DISOMQD2	Supportive	Autosomal recessive	[25]
Cowden disease	DISMYKCE	Disputed	Genetic Variation	[5]
Cockayne syndrome	DISW6GL2	Limited	Biomarker	[26]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[27]

12 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 General transcription factor IIH subunit 5 (GTF2H5).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[31]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of General transcription factor IIH subunit 5 (GTF2H5).	[33]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of General transcription factor IIH subunit 5 (GTF2H5).	[33]
Arecoline	DMFJZK3	Phase 1	Arecoline decreases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[37]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of General transcription factor IIH subunit 5 (GTF2H5).	[38]

References

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• [17] The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large-scale deletions associated with Werdnig-Hoffmann disease.Am J Hum Genet. 1997 Jan;60(1):72-9.
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