Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1V8H40)

• DOT Name: Spindle assembly abnormal protein 6 homolog (SASS6)
• Synonyms: HsSAS-6
• Gene Name: SASS6
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Delirium
  Lung adenocarcinoma
  Microcephaly 14, primary, autosomal recessive
  Isolated congenital microcephaly
  Autosomal recessive primary microcephaly
  Melanocytic nevus
• UniProt ID: SAS6_HUMAN
• PDB ID: 6YS4; 6Z4A
• Pfam ID: PF16531 ; PF18594
• Sequence:
  MSQVLFHQLVPLQVKCKDCEERRVSIRMSIELQSVSNPVHRKDLVIRLTDDTDPFFLYNL
  VISEEDFQSLKFQQGLLVDFLAFPQKFIDLLQQCTQEHAKEIPRFLLQLVSPAAILDNSP
  AFLNVVETNPFKHLTHLSLKLLPGNDVEIKKFLAGCLKCSKEEKLSLMQSLDDATKQLDF
  TRKTLAEKKQELDKLRNEWASHTAALTNKHSQELTNEKEKALQAQVQYQQQHEQQKKDLE
  ILHQQNIHQLQNRLSELEAANKDLTERKYKGDSTIRELKAKLSGVEEELQRTKQEVLSLR
  RENSTLDVECHEKEKHVNQLQTKVAVLEQEIKDKDQLVLRTKEAFDTIQEQKVVLEENGE
  KNQVQLGKLEATIKSLSAELLKANEIIKKLQGDLKTLMGKLKLKNTVTIQQEKLLAEKEE
  KLQKEQKELQDVGQSLRIKEQEVCKLQEQLEATVKKLEESKQLLKNNEKLITWLNKELNE
  NQLVRKQDVLGPSTTPPAHSSSNTIRSGISPNLNVVDGRLTYPTCGIGYPVSSAFAFQNT
  FPHSISAKNTSHPGSGTKVQFNLQFTKPNASLGDVQSGATISMPCSTDKENGENVGLESK
  YLKKREDSIPLRGLSQNLFSNSDHQRDGTLGALHTSSKPTALPSASSAYFPGQLPNS
• Function: Central scaffolding component of the centrioles ensuring their 9-fold symmetry. Required for centrosome biogenesis and duplication: required both for mother-centriole-dependent centriole duplication and deuterosome-dependent centriole amplification in multiciliated cells. Overexpression results in excess foci-bearing centriolar markers. Required for the recruitment of STIL to the procentriole and for STIL-mediated centriole amplification.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Delirium	DIS2OKP1	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]
Microcephaly 14, primary, autosomal recessive	DISLIM3D	Strong	Autosomal recessive	[3]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[4]
Autosomal recessive primary microcephaly	DIS29IE3	Supportive	Autosomal recessive	[3]
Melanocytic nevus	DISYS32D	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Spindle assembly abnormal protein 6 homolog (SASS6).	[6]

14 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 Spindle assembly abnormal protein 6 homolog (SASS6).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Spindle assembly abnormal protein 6 homolog (SASS6).	[18]

References

• [1] SASS6 overexpression is associated with mitotic chromosomal abnormalities and a poor prognosis in patients with colorectal cancer.Oncol Rep. 2015 Aug;34(2):727-38. doi: 10.3892/or.2015.4014. Epub 2015 May 28.
• [2] Sedation Practice in Extracorporeal Membrane Oxygenation-Treated Patients with Acute Respiratory Distress Syndrome: A Retrospective Study.ASAIO J. 2018 Jul/Aug;64(4):544-551. doi: 10.1097/MAT.0000000000000658.
• [3] A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family. Hum Mol Genet. 2014 Nov 15;23(22):5940-9. doi: 10.1093/hmg/ddu318. Epub 2014 Jun 20.
• [4] Novel SASS6 compound heterozygous mutations in a Chinese family with primary autosomal recessive microcephaly.Clin Chim Acta. 2019 Apr;491:15-18. doi: 10.1016/j.cca.2019.01.007. Epub 2019 Jan 10.
• [5] Malignant melanoma withareas ofrhabdomyosarcomatousdifferentiation arising in a giant congenital nevus with RAF1 gene fusion.Pigment Cell Melanoma Res. 2019 Sep;32(5):708-713. doi: 10.1111/pcmr.12785. Epub 2019 Apr 21.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells. Life Sci Alliance. 2022 Nov 16;6(1):e202201499. doi: 10.26508/lsa.202201499. Print 2023 Jan.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [18] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.