Details of Drug Off-Target (DOT)

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

• DOT Name: Surfeit locus protein 1 (SURF1)
• Gene Name: SURF1
• Related Disease:
  Leigh syndrome
  Alzheimer disease
  Cerebellar ataxia
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease type 4K
  Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type
  Cytochrome-c oxidase deficiency disease
  Demyelinating polyneuropathy
  Glycine encephalopathy
  Hyperinsulinemia
  Hypertrichosis
  Intellectual disability
  Mitochondrial disease
  Movement disorder
  Peripheral neuropathy
  Polyneuropathy
  Lactic acidosis
  Leigh syndrome with cardiomyopathy
  Obsolete Leigh syndrome with leukodystrophy
  Hypertrophic cardiomyopathy
  Leukodystrophy
  Nervous system disease
• UniProt ID: SURF1_HUMAN
• Pfam ID: PF02104
• Sequence:
  MAAVAALQLGLRAAGLGRAPASAAWRSVLRVSPRPGVAWRPSRCGSSAAEASATKAEDDS
  FLQWVLLLIPVTAFGLGTWQVQRRKWKLNLIAELESRVLAEPVPLPADPMELKNLEYRPV
  KVRGCFDHSKELYMMPRTMVDPVREAREGGLISSSTQSGAYVVTPFHCTDLGVTILVNRG
  FVPRKKVNPETRQKGQIEGEVDLIGMVRLTETRQPFVPENNPERNHWHYRDLEAMARITG
  AEPIFIDANFQSTVPGGPIGGQTRVTLRNEHLQYIVTWYGLSAATSYLWFKKFLRGTPGV
• Function: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[3]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[4]
Charcot-Marie-Tooth disease type 4K	DIS45SDP	Strong	Autosomal recessive	[4]
Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	DISVZ0PJ	Strong	Biomarker	[5]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Genetic Variation	[6]
Demyelinating polyneuropathy	DIS7IO4W	Strong	Genetic Variation	[7]
Glycine encephalopathy	DISI2XE5	Strong	Genetic Variation	[8]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[9]
Hypertrichosis	DISZUK5W	Strong	Genetic Variation	[10]
Intellectual disability	DISMBNXP	Strong	Biomarker	[11]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[12]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[7]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[13]
Polyneuropathy	DISB9G3W	Strong	Biomarker	[4]
Lactic acidosis	DISZI1ZK	moderate	Biomarker	[4]
Leigh syndrome with cardiomyopathy	DIS2UELC	Supportive	Autosomal recessive	[14]
Obsolete Leigh syndrome with leukodystrophy	DISABU9D	Supportive	Autosomal recessive	[14]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Genetic Variation	[15]
Leukodystrophy	DISVY1TT	Limited	Genetic Variation	[16]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Surfeit locus protein 1 (SURF1).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Surfeit locus protein 1 (SURF1).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Surfeit locus protein 1 (SURF1).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Surfeit locus protein 1 (SURF1).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Surfeit locus protein 1 (SURF1).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Surfeit locus protein 1 (SURF1).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Surfeit locus protein 1 (SURF1).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Surfeit locus protein 1 (SURF1).	[25]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Surfeit locus protein 1 (SURF1).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Surfeit locus protein 1 (SURF1).	[27]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Surfeit locus protein 1 (SURF1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Surfeit locus protein 1 (SURF1).	[28]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Surfeit locus protein 1 (SURF1).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Surfeit locus protein 1 (SURF1).	[30]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Genetic association of the cytochrome c oxidase-related genes with Alzheimer's disease in Han Chinese.Neuropsychopharmacology. 2018 Oct;43(11):2264-2276. doi: 10.1038/s41386-018-0144-3. Epub 2018 Jul 6.
• [3] Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency.Mitochondrion. 2016 Nov;31:84-88. doi: 10.1016/j.mito.2016.10.004. Epub 2016 Oct 15.
• [4] SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology. 2013 Oct 22;81(17):1523-30. doi: 10.1212/WNL.0b013e3182a4a518. Epub 2013 Sep 11.
• [5] Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency.Pediatr Res. 2006 Jan;59(1):21-6. doi: 10.1203/01.pdr.0000190572.68191.13. Epub 2005 Dec 2.
• [6] Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects.Biochim Biophys Acta. 2016 Apr;1862(4):705-715. doi: 10.1016/j.bbadis.2016.01.007. Epub 2016 Jan 13.
• [7] Peripheral neuropathy in genetically characterized patients with mitochondrial disorders: A study from south India.Mitochondrion. 2016 Mar;27:1-5. doi: 10.1016/j.mito.2015.12.009. Epub 2016 Jan 4.
• [8] Brain imaging and genetic risk in the pediatric population, part 1: inherited metabolic diseases.Neuroimaging Clin N Am. 2015 Feb;25(1):31-51. doi: 10.1016/j.nic.2014.09.004.
• [9] Sco2 deficient mice develop increased adiposity and insulin resistance.Mol Cell Endocrinol. 2017 Nov 5;455:103-114. doi: 10.1016/j.mce.2017.03.019. Epub 2017 Apr 18.
• [10] Hypertrichosis in presymptomatic mitochondrial disease.J Inherit Metab Dis. 2013 Nov;36(6):1081-2. doi: 10.1007/s10545-013-9593-3. Epub 2013 Feb 14.
• [11] Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.
• [12] Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.Brain. 2016 Nov 1;139(11):2844-2854. doi: 10.1093/brain/aww221.
• [13] A novel SURF1 mutation results in Leigh syndrome with peripheral neuropathy caused by cytochrome c oxidase deficiency.Neuromuscul Disord. 2000 Aug;10(6):450-3. doi: 10.1016/s0960-8966(99)00122-4.
• [14] SURF1 deficiency: a multi-centre natural history study. Orphanet J Rare Dis. 2013 Jul 5;8:96. doi: 10.1186/1750-1172-8-96.
• [15] Mutation screening in patients with isolated cytochrome c oxidase deficiency.Pediatr Res. 2003 Feb;53(2):224-30. doi: 10.1203/01.PDR.0000048100.91730.6A.
• [16] SURF-1 gene mutation associated with leukoencephalopathy in a 2-year-old.J Child Neurol. 2009 Oct;24(10):1296-301. doi: 10.1177/0883073809333543.
• [17] Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations.Am J Physiol Cell Physiol. 2004 Nov;287(5):C1384-8. doi: 10.1152/ajpcell.00286.2004. Epub 2004 Jul 21.
• [18] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [19] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [20] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [21] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [24] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [25] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [26] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [27] Beneficial effects of resveratrol on respiratory chain defects in patients' fibroblasts involve estrogen receptor and estrogen-related receptor alpha signaling. Hum Mol Genet. 2014 Apr 15;23(8):2106-19.
• [28] 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.
• [29] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [30] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.