Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3PJCT)

• DOT Name: Regulator of telomere elongation helicase 1 (RTEL1)
• Synonyms: EC 3.6.4.12; Novel helicase-like
• Gene Name: RTEL1
• Related Disease:
  Dyskeratosis congenita, autosomal recessive 5
  Small lymphocytic lymphoma
  Adult lymphoma
  Atopic dermatitis
  Central nervous system neoplasm
  Classic Hodgkin lymphoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Follicular lymphoma
  Glioma
  Hepatitis C virus infection
  leukaemia
  Leukemia
  Lung carcinoma
  Lung neoplasm
  Lymphoma
  Lymphoma, non-Hodgkin, familial
  Mantle cell lymphoma
  Nasopharyngeal carcinoma
  Neoplasm
  Non-hodgkin lymphoma
  Pancytopenia
  Pediatric lymphoma
  Plasma cell myeloma
  Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3
  Acute myelogenous leukaemia
  Advanced cancer
  Brain neoplasm
  Dyskeratosis congenita, X-linked
  Pulmonary fibrosis
  Dyskeratosis congenita
  Hoyeraal-Hreidarsson syndrome
  Burkitt lymphoma
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Asthma
  B-cell neoplasm
  Crohn disease
  Glioblastoma multiforme
  Lung cancer
  Malignant glioma
  Mixed glioma
  Ulcerative colitis
• UniProt ID: RTEL1_HUMAN
• PDB ID: 7WU8
• EC Number: 3.6.4.12
• Pfam ID: PF06733 ; PF13307
• Sequence:
  MPKIVLNGVTVDFPFQPYKCQQEYMTKVLECLQQKVNGILESPTGTGKTLCLLCTTLAWR
  EHLRDGISARKIAERAQGELFPDRALSSWGNAAAAAGDPIACYTDIPKIIYASRTHSQLT
  QVINELRNTSYRPKVCVLGSREQLCIHPEVKKQESNHLQIHLCRKKVASRSCHFYNNVEE
  KSLEQELASPILDIEDLVKSGSKHRVCPYYLSRNLKQQADIIFMPYNYLLDAKSRRAHNI
  DLKGTVVIFDEAHNVEKMCEESASFDLTPHDLASGLDVIDQVLEEQTKAAQQGEPHPEFS
  ADSPSPGLNMELEDIAKLKMILLRLEGAIDAVELPGDDSGVTKPGSYIFELFAEAQITFQ
  TKGCILDSLDQIIQHLAGRAGVFTNTAGLQKLADIIQIVFSVDPSEGSPGSPAGLGALQS
  YKVHIHPDAGHRRTAQRSDAWSTTAARKRGKVLSYWCFSPGHSMHELVRQGVRSLILTSG
  TLAPVSSFALEMQIPFPVCLENPHIIDKHQIWVGVVPRGPDGAQLSSAFDRRFSEECLSS
  LGKALGNIARVVPYGLLIFFPSYPVMEKSLEFWRARDLARKMEALKPLFVEPRSKGSFSE
  TISAYYARVAAPGSTGATFLAVCRGKASEGLDFSDTNGRGVIVTGLPYPPRMDPRVVLKM
  QFLDEMKGQGGAGGQFLSGQEWYRQQASRAVNQAIGRVIRHRQDYGAVFLCDHRFAFADA
  RAQLPSWVRPHVRVYDNFGHVIRDVAQFFRVAERTMPAPAPRATAPSVRGEDAVSEAKSP
  GPFFSTRKAKSLDLHVPSLKQRSSGSPAAGDPESSLCVEYEQEPVPARQRPRGLLAALEH
  SEQRAGSPGEEQAHSCSTLSLLSEKRPAEEPRGGRKKIRLVSHPEEPVAGAQTDRAKLFM
  VAVKQELSQANFATFTQALQDYKGSDDFAALAACLGPLFAEDPKKHNLLQGFYQFVRPHH
  KQQFEEVCIQLTGRGCGYRPEHSIPRRQRAQPVLDPTGRTAPDPKLTVSTAAAQQLDPQE
  HLNQGRPHLSPRPPPTGDPGSQPQWGSGVPRAGKQGQHAVSAYLADARRALGSAGCSQLL
  AALTAYKQDDDLDKVLAVLAALTTAKPEDFPLLHRFSMFVRPHHKQRFSQTCTDLTGRPY
  PGMEPPGPQEERLAVPPVLTHRAPQPGPSRSEKTGKTQSKISSFLRQRPAGTVGAGGEDA
  GPSQSSGPPHGPAASEWGL
• Function: ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.
• Reactome Pathway:
  Cytosolic iron-sulfur cluster assembly (R-HSA-2564830)
  Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) (R-HSA-5693554)
  Telomere Extension By Telomerase (R-HSA-171319)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dyskeratosis congenita, autosomal recessive 5	DIS7H2M2	Definitive	Autosomal recessive	[1]
Small lymphocytic lymphoma	DIS30POX	Definitive	Biomarker	[2]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[4]
Central nervous system neoplasm	DISFC18W	Strong	Genetic Variation	[5]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[7]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[7]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[7]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[7]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[7]
Follicular lymphoma	DISVEUR6	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Genetic Variation	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[10]
leukaemia	DISS7D1V	Strong	Biomarker	[11]
Leukemia	DISNAKFL	Strong	Genetic Variation	[3]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[12]
Lung neoplasm	DISVARNB	Strong	Biomarker	[13]
Lymphoma	DISN6V4S	Strong	Biomarker	[3]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[14]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[15]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[14]
Pancytopenia	DISVKEHV	Strong	Biomarker	[17]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[3]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[3]
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	DISK1NTB	Strong	Autosomal dominant	[18]
Acute myelogenous leukaemia	DISCSPTN	Moderate	Autosomal dominant	[19]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[20]
Brain neoplasm	DISY3EKS	moderate	Biomarker	[21]
Dyskeratosis congenita, X-linked	DISJ3Y69	moderate	Genetic Variation	[22]
Pulmonary fibrosis	DISQKVLA	moderate	Biomarker	[23]
Dyskeratosis congenita	DISSXV0K	Supportive	Autosomal dominant	[1]
Hoyeraal-Hreidarsson syndrome	DISAUR8F	Supportive	Autosomal dominant	[24]
Burkitt lymphoma	DIS9D5XU	Disputed	Altered Expression	[25]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[26]
Adult glioblastoma	DISVP4LU	Limited	Genetic Variation	[27]
Asthma	DISW9QNS	Limited	Genetic Variation	[28]
B-cell neoplasm	DISVY326	Limited	Biomarker	[29]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[30]
Glioblastoma multiforme	DISK8246	Limited	Genetic Variation	[9]
Lung cancer	DISCM4YA	Limited	Biomarker	[31]
Malignant glioma	DISFXKOV	Limited	Genetic Variation	[32]
Mixed glioma	DIS64UY3	Limited	Biomarker	[33]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Regulator of telomere elongation helicase 1 (RTEL1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Regulator of telomere elongation helicase 1 (RTEL1).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Regulator of telomere elongation helicase 1 (RTEL1).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Regulator of telomere elongation helicase 1 (RTEL1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Regulator of telomere elongation helicase 1 (RTEL1).	[37]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Regulator of telomere elongation helicase 1 (RTEL1).	[38]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Regulator of telomere elongation helicase 1 (RTEL1).	[39]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Regulator of telomere elongation helicase 1 (RTEL1).	[40]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Regulator of telomere elongation helicase 1 (RTEL1).	[36]

References

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