Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHV3EFE)

• DOT Name: Probable ATP-dependent DNA helicase HFM1 (HFM1)
• Synonyms: EC 3.6.4.12; SEC63 domain-containing protein 1
• Gene Name: HFM1
• Related Disease:
  Hutchinson-Gilford progeria syndrome
  Myocardial infarction
  XFE progeroid syndrome
  Autosomal dominant familial periodic fever
  Bloom syndrome
  Breast cancer
  Breast carcinoma
  Cockayne syndrome
  Female hypogonadism
  Graves disease
  Myositis disease
  Orofaciodigital syndrome
  Orofaciodigital syndrome I
  Rothmund-Thomson syndrome
  Systemic lupus erythematosus
  Systemic sclerosis
  Werner syndrome
  Xeroderma pigmentosum
  Advanced cancer
  Rapadilino syndrome
  Small lymphocytic lymphoma
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Colorectal carcinoma
  Hepatitis C virus infection
  Hepatitis E virus infection
  Premature ovarian failure 9
  Xeroderma pigmentosum group D
• UniProt ID: HFM1_HUMAN
• EC Number: 3.6.4.12
• Pfam ID: PF00270 ; PF00271 ; PF02889
• Sequence:
  MLKSNDCLFSLENLFFEKPDEVENHPDNEKSLDWFLPPAPLISEIPDTQELEEELESHKL
  LGQEKRPKMLTSNLKITNEDTNYISLTQKFQFAFPSDKYEQDDLNLEGVGNNDLSHIAGK
  LTYASQKYKNHIGTEIAPEKSVPDDTKLVNFAEDKGESTSVFRKRLFKISDNIHGSAYSN
  DNELDSHIGSVKIVQTEMNKGKSRNYSNSKQKFQYSANVFTANNAFSASEIGEGMFKAPS
  FSVAFQPHDIQEVTENGLGSLKAVTEIPAKFRSIFKEFPYFNYIQSKAFDDLLYTDRNFV
  ICAPTGSGKTVVFELAITRLLMEVPLPWLNIKIVYMAPIKALCSQRFDDWKEKFGPIGLN
  CKELTGDTVMDDLFEIQHAHIIMTTPEKWDSMTRKWRDNSLVQLVRLFLIDEVHIVKDEN
  RGPTLEVVVSRMKTVQSVSQTLKNTSTAIPMRFVAVSATIPNAEDIAEWLSDGERPAVCL
  KMDESHRPVKLQKVVLGFPCSSNQTEFKFDLTLNYKIASVIQMYSDQKPTLVFCATRKGV
  QQAASVLVKDAKFIMTVEQKQRLQKYAYSVRDSKLRDILKDGAAYHHAGMELSDRKVVEG
  AFTVGDLPVLFTTSTLAMGVNLPAHLVVIKSTMHYAGGLFEEYSETDILQMIGRAGRPQF
  DTTATAVIMTRLSTRDKYIQMLACRDTVESSLHRHLIEHLNAEIVLHTITDVNIAVEWIR
  STLLYIRALKNPSHYGFASGLNKDGIEAKLQELCLKNLNDLSSLDLIKMDEGVNFKPTEA
  GRLMAWYYITFETVKKFYTISGKETLSDLVTLIAGCKEFLDIQLRINEKKTLNTLNKDPN
  RITIRFPMEGRIKTREMKVNCLIQAQLGCIPIQDFALTQDTAKIFRHGSRITRWLSDFVA
  AQEKKFAVLLNSLILAKCFRCKLWENSLHVSKQLEKIGITLSNAIVNAGLTSFKKIEETD
  ARELELILNRHPPFGTQIKETVMYLPKYELKVEQITRYSDTTAEILVTVILRNFEQLQTK
  RTASDSHYVTLIIGDADNQVVYLHKITDSVLLKAGSWAKKIAVKRALKSEDLSINLISSE
  FVGLDIQQKLTVFYLEPKRFGNQITMQRKSETQISHSKHSDISTIAGPNKGTTASKKPGN
  RECNHLCKSKHTCGHDCCKIGVAQKSEIKESTISSYLSDLRNRNAVSSVPPVKRLKIQMN
  KSQSVDLKEFGFTPKPSLPSISRSEYLNISELPIMEQWDQPEIYGKVRQEPSEYQDKEVL
  NVNFELGNEVWDDFDDENLEVTSFSTDTEKTKISGFGNTLSSSTRGSKLPLQESKSKFQR
  EMSNSFVSSHEMSDISLSNSAMPKFSASSMTKLPQQAGNAVIVHFQERKPQNLSPEIEKQ
  CFTFSEKNPNSSNYKKVDFFIRNSECKKEVDFSMYHPDDEADEMKSLLGIFDGIF
• Function: Required for crossover formation and complete synapsis of homologous chromosomes during meiosis.
• Tissue Specificity: Preferentially expressed in testis and ovary.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hutchinson-Gilford progeria syndrome	DISY55BU	Definitive	Biomarker	[1]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[2]
XFE progeroid syndrome	DISVZ5JW	Definitive	Biomarker	[1]
Autosomal dominant familial periodic fever	DISCRNV1	Strong	Genetic Variation	[3]
Bloom syndrome	DISKXQ7J	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cockayne syndrome	DISW6GL2	Strong	Genetic Variation	[6]
Female hypogonadism	DISWASB4	Strong	Genetic Variation	[7]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[8]
Myositis disease	DISCIXF0	Strong	Biomarker	[9]
Orofaciodigital syndrome	DISSB296	Strong	Genetic Variation	[10]
Orofaciodigital syndrome I	DIST27XL	Strong	Genetic Variation	[10]
Rothmund-Thomson syndrome	DISGVBCV	Strong	Genetic Variation	[11]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[12]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[13]
Werner syndrome	DISZY45W	Strong	Genetic Variation	[14]
Xeroderma pigmentosum	DISQ9H19	Strong	Genetic Variation	[15]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[6]
Rapadilino syndrome	DISJX57C	moderate	Genetic Variation	[16]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[17]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Disputed	Autosomal recessive	[18]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[19]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[20]
Hepatitis E virus infection	DIS0TXIR	Limited	Genetic Variation	[21]
Premature ovarian failure 9	DISJGHV0	Limited	Unknown	[22]
Xeroderma pigmentosum group D	DISFFE93	Limited	Biomarker	[23]

4 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 Probable ATP-dependent DNA helicase HFM1 (HFM1).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Probable ATP-dependent DNA helicase HFM1 (HFM1).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable ATP-dependent DNA helicase HFM1 (HFM1).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Probable ATP-dependent DNA helicase HFM1 (HFM1).	[28]

1 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 increases the methylation of Probable ATP-dependent DNA helicase HFM1 (HFM1).	[26]

References

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• [4] The Werner syndrome RECQ helicase targets G4 DNA in human cells to modulate transcription.Hum Mol Genet. 2016 May 15;25(10):2060-2069. doi: 10.1093/hmg/ddw079. Epub 2016 Mar 16.
• [5] BACH1 Ser919Pro variant and breast cancer risk.BMC Cancer. 2006 Jan 24;6:19. doi: 10.1186/1471-2407-6-19.
• [6] Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype.Sci Rep. 2017 Mar 9;7:44081. doi: 10.1038/srep44081.
• [7] A novel heterozygous splice-altering mutation in HFM1 may be a cause of premature ovarian insufficiency.J Ovarian Res. 2019 Jul 6;12(1):61. doi: 10.1186/s13048-019-0537-x.
• [8] The A946T polymorphism in the interferon induced helicase gene does not confer susceptibility to Graves' disease in Chinese population.Endocrine. 2007 Oct;32(2):143-7. doi: 10.1007/s12020-007-9024-z. Epub 2007 Nov 17.
• [9] Hyperacute muscle weakness in an unusual coexistence of antisignal recognition particle and anti-Mi-2 antibodies.BMJ Case Rep. 2017 Jul 18;2017:bcr2017219221. doi: 10.1136/bcr-2017-219221.
• [10] Confirmation that mutations in DDX59 cause an autosomal recessive form of oral-facial-digital syndrome: Further delineation of the DDX59 phenotype in two new families.Eur J Med Genet. 2017 Oct;60(10):527-532. doi: 10.1016/j.ejmg.2017.07.009. Epub 2017 Jul 12.
• [11] Rothmund-Thomson syndrome.Orphanet J Rare Dis. 2010 Jan 29;5:2. doi: 10.1186/1750-1172-5-2.
• [12] Autoimmune disease associated IFIH1 single nucleotide polymorphism related with IL-18 serum levels in Chinese systemic lupus erythematosus patients.Sci Rep. 2018 Jun 21;8(1):9442. doi: 10.1038/s41598-018-27782-7.
• [13] Altered MCM protein levels and autophagic flux in aged and systemic sclerosis dermal fibroblasts.J Invest Dermatol. 2014 Sep;134(9):2321-2330. doi: 10.1038/jid.2014.69. Epub 2014 Feb 4.
• [14] RECQ helicase disease and related progeroid syndromes: RECQ2018 meeting.Mech Ageing Dev. 2018 Jul;173:80-83. doi: 10.1016/j.mad.2018.05.002. Epub 2018 May 9.
• [15] Differential developmental expression of the rep B and rep D xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum.Nucleic Acids Res. 1997 Jun 15;25(12):2365-74. doi: 10.1093/nar/25.12.2365.
• [16] A patient with Rothmund-Thomson syndrome and all features of RAPADILINO.Arch Dermatol. 2005 May;141(5):617-20. doi: 10.1001/archderm.141.5.617.
• [17] Detection of a novel truncating Merkel cell polyomavirus large T antigen deletion in chronic lymphocytic leukemia cells.Blood. 2010 Dec 9;116(24):5280-4. doi: 10.1182/blood-2010-02-269829. Epub 2010 Sep 3.
• [18] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [19] Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas.Oncogene. 2002 Sep 12;21(41):6387-94. doi: 10.1038/sj.onc.1205751.
• [20] NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA.J Virol. 2017 Dec 14;92(1):e01253-17. doi: 10.1128/JVI.01253-17. Print 2018 Jan 1.
• [21] Genotyping of hepatitis E virus in clinical specimens by restriction endonuclease analysis.J Virol Methods. 1998 Jan;70(1):71-8. doi: 10.1016/s0166-0934(97)00172-9.
• [22] Mutations in HFM1 in recessive primary ovarian insufficiency. N Engl J Med. 2014 Mar 6;370(10):972-4. doi: 10.1056/NEJMc1310150.
• [23] Homozygous Wildtype of XPD K751Q Polymorphism Is Associated with Increased Risk of Nasopharyngeal Carcinoma in Malaysian Population.PLoS One. 2015 Jun 18;10(6):e0130530. doi: 10.1371/journal.pone.0130530. eCollection 2015.
• [24] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [25] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [26] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [27] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [28] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.