Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPD1DIU)

• DOT Name: General transcription factor IIH subunit 4 (GTF2H4)
• Synonyms: Basic transcription factor 2 52 kDa subunit; BTF2 p52; General transcription factor IIH polypeptide 4; TFIIH basal transcription factor complex p52 subunit
• Gene Name: GTF2H4
• Related Disease:
  Parkinson disease
  Type-1/2 diabetes
  Xeroderma pigmentosum group B
  Ataxia-telangiectasia
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Classic Hodgkin lymphoma
  Cockayne syndrome
  Colon carcinoma
  Cytomegalovirus infection
  Gastric cancer
  Glioblastoma multiforme
  Graves disease
  Melanoma
  Neoplasm
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Sarcoidosis
  Skin disease
  Spinal muscular atrophy
  Stomach cancer
  T-cell lymphoma
  Triple negative breast cancer
  Uveal Melanoma
  Vitiligo
  Xeroderma pigmentosum group D
  Clear cell renal carcinoma
  Gastritis
  Head-neck squamous cell carcinoma
  Renal cell carcinoma
  Skin cancer
  Cowden disease
  Acute myelogenous leukaemia
  Adenocarcinoma
  Anaplastic large cell lymphoma
  Bladder cancer
  Congenital contractural arachnodactyly
  Lung cancer
  Lung carcinoma
  Malaria
  Primary cutaneous T-cell lymphoma
  Trichothiodystrophy
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: TF2H4_HUMAN
• PDB ID: 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: PF03849 ; PF18307
• Sequence:
  MESTPSRGLNRVHLQCRNLQEFLGGLSPGVLDRLYGHPATCLAVFRELPSLAKNWVMRML
  FLEQPLPQAAVALWVKKEFSKAQEESTGLLSGLRIWHTQLLPGGLQGLILNPIFRQNLRI
  ALLGGGKAWSDDTSQLGPDKHARDVPSLDKYAEERWEVVLHFMVGSPSAAVSQDLAQLLS
  QAGLMKSTEPGEPPCITSAGFQFLLLDTPAQLWYFMLQYLQTAQSRGMDLVEILSFLFQL
  SFSTLGKDYSVEGMSDSLLNFLQHLREFGLVFQRKRKSRRYYPTRLAINLSSGVSGAGGT
  VHQPGFIVVETNYRLYAYTESELQIALIALFSEMLYRFPNMVVAQVTRESVQQAIASGIT
  AQQIIHFLRTRAHPVMLKQTPVLPPTITDQIRLWELERDRLRFTEGVLYNQFLSQVDFEL
  LLAHARELGVLVFENSAKRLMVVTPAGHSDVKRFWKRQKHSS
• 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.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Nucleotide excision repair (hsa03420)
  Viral carcinogenesis (hsa05203)
• 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

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[2]
Xeroderma pigmentosum group B	DIS1EFEV	Definitive	Biomarker	[3]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[8]
Cockayne syndrome	DISW6GL2	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[11]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[13]
Graves disease	DISU4KOQ	Strong	Altered Expression	[14]
Melanoma	DIS1RRCY	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[17]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[18]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[19]
Skin disease	DISDW8R6	Strong	Altered Expression	[20]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[12]
T-cell lymphoma	DISSXRTQ	Strong	Genetic Variation	[22]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[23]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[24]
Vitiligo	DISR05SL	Strong	Genetic Variation	[25]
Xeroderma pigmentosum group D	DISFFE93	Strong	Biomarker	[26]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[27]
Gastritis	DIS8G07K	moderate	Genetic Variation	[28]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[29]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[27]
Skin cancer	DISTM18U	moderate	Altered Expression	[30]
Cowden disease	DISMYKCE	Disputed	Genetic Variation	[31]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[32]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[33]
Anaplastic large cell lymphoma	DISP4D1R	Limited	Biomarker	[34]
Bladder cancer	DISUHNM0	Limited	Biomarker	[35]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[36]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[37]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[37]
Malaria	DISQ9Y50	Limited	Altered Expression	[38]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Biomarker	[39]
Trichothiodystrophy	DISOMQD2	Limited	Altered Expression	[40]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[35]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[35]

15 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 General transcription factor IIH subunit 4 (GTF2H4).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[46]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of General transcription factor IIH subunit 4 (GTF2H4).	[47]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[49]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of General transcription factor IIH subunit 4 (GTF2H4).	[47]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[50]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[51]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[54]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[55]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of General transcription factor IIH subunit 4 (GTF2H4).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of General transcription factor IIH subunit 4 (GTF2H4).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of General transcription factor IIH subunit 4 (GTF2H4).	[52]

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