Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFQJG3C)

• DOT Name: N-acylneuraminate cytidylyltransferase (CMAS)
• Synonyms: EC 2.7.7.43; CMP-N-acetylneuraminic acid synthase; CMP-NeuNAc synthase
• Gene Name: CMAS
• Related Disease:
  Aural atresia, congenital
  Autism
  Clear cell renal carcinoma
  Eosinophilic granulomatosis with polyangiitis
  Fatty liver disease
  Gastrointestinal stromal tumour
  Glioblastoma multiforme
  Hyperthyroidism
  Immunodeficiency
  Malignant soft tissue neoplasm
  Norrie disease
  Obesity
  Paraganglioma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Sarcoma
  Transitional cell carcinoma
  Tuberculosis
  Urothelial carcinoma
  Head-neck squamous cell carcinoma
  Melanoma
  Advanced cancer
  Chronic kidney disease
  Colorectal carcinoma
  Intellectual disability
  Vasculitis
• UniProt ID: NEUA_HUMAN
• EC Number: 2.7.7.43
• Pfam ID: PF02348
• Sequence:
  MDSVEKGAATSVSNPRGRPSRGRPPKLQRNSRGGQGRGVEKPPHLAALILARGGSKGIPL
  KNIKHLAGVPLIGWVLRAALDSGAFQSVWVSTDHDEIENVAKQFGAQVHRRSSEVSKDSS
  TSLDAIIEFLNYHNEVDIVGNIQATSPCLHPTDLQKVAEMIREEGYDSVFSVVRRHQFRW
  SEIQKGVREVTEPLNLNPAKRPRRQDWDGELYENGSFYFAKRHLIEMGYLQGGKMAYYEM
  RAEHSVDIDVDIDWPIAEQRVLRYGYFGKEKLKEIKLLVCNIDGCLTNGHIYVSGDQKEI
  ISYDVKDAIGISLLKKSGIEVRLISERACSKQTLSSLKLDCKMEVSVSDKLAVVDEWRKE
  MGLCWKEVAYLGNEVSDEECLKRVGLSGAPADACSTAQKAVGYICKCNGGRGAIREFAEH
  ICLLMEKVNNSCQK
• Function: Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity toward NeuNAc, N-glycolylneuraminic acid (Neu5Gc) or 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN).
• Tissue Specificity: Ubiquitously expressed. Expressed in pancreas, kidney, liver, skeletal muscle, lung, placenta, brain, heart, colon, PBL, small intestine, ovary, testis, prostate, thymus and spleen.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway: Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aural atresia, congenital	DISCP7UV	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Eosinophilic granulomatosis with polyangiitis	DIS7ITOG	Strong	Biomarker	[4]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[5]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Genetic Variation	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[7]
Hyperthyroidism	DISX87ZH	Strong	Biomarker	[8]
Immunodeficiency	DIS093I0	Strong	Biomarker	[7]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[6]
Norrie disease	DISOCDDU	Strong	Biomarker	[9]
Obesity	DIS47Y1K	Strong	Genetic Variation	[5]
Paraganglioma	DIS2XXH5	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[11]
Sarcoma	DISZDG3U	Strong	Biomarker	[6]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[12]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[13]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[14]
Melanoma	DIS1RRCY	Disputed	Biomarker	[15]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[16]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[17]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[18]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[19]
Vasculitis	DISQRKDX	Limited	Biomarker	[4]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
CMP-sialic acid	DMH48YE	Investigative	N-acylneuraminate cytidylyltransferase (CMAS) affects the abundance of CMP-sialic acid.	[25]

5 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 N-acylneuraminate cytidylyltransferase (CMAS).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of N-acylneuraminate cytidylyltransferase (CMAS).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of N-acylneuraminate cytidylyltransferase (CMAS).	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of N-acylneuraminate cytidylyltransferase (CMAS).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of N-acylneuraminate cytidylyltransferase (CMAS).	[24]

References

• [1] Subarachnoid extension of lobar hemorrhage on acute/subacute MRI is associated with cerebral amyloid angiopathy criteria.Acta Neurol Belg. 2020 Aug;120(4):863-866. doi: 10.1007/s13760-018-01060-9. Epub 2018 Dec 11.
• [2] The ADOS calibrated severity score: relationship to phenotypic variables and stability over time.Autism Res. 2012 Aug;5(4):267-76. doi: 10.1002/aur.1238. Epub 2012 May 24.
• [3] Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion.Eur Urol. 2019 May;75(5):752-763. doi: 10.1016/j.eururo.2018.09.030. Epub 2018 Oct 4.
• [4] The leukotriene receptor antagonist Montelukast can induce adverse skin reactions in asthmatic patients.Pulm Pharmacol Ther. 2020 Feb;60:101875. doi: 10.1016/j.pupt.2019.101875. Epub 2019 Dec 11.
• [5] Genetic resistance to liver fibrosis on A/J mouse chromosome 17.Alcohol Clin Exp Res. 2013 Oct;37(10):1668-79. doi: 10.1111/acer.12157. Epub 2013 Jun 13.
• [6] The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications.J Intern Med. 2009 Jul;266(1):43-52. doi: 10.1111/j.1365-2796.2009.02110.x.
• [7] Establishment and genetic characterization of ANGM-CSS, a novel, immortal cell line derived from a human glioblastoma multiforme.Int J Oncol. 2014 Mar;44(3):717-24. doi: 10.3892/ijo.2013.2224. Epub 2013 Dec 23.
• [8] Antithyroid drug treatment for Graves' disease: baseline predictive models of relapse after treatment for a patient-tailored management.J Endocrinol Invest. 2018 Dec;41(12):1425-1432. doi: 10.1007/s40618-018-0918-9. Epub 2018 Jun 26.
• [9] Nutritional dwarfing: a growth abnormality associated with reduced erythrocyte Na+,K(+)-ATPase activity.Am J Clin Nutr. 1991 Dec;54(6):997-1004. doi: 10.1093/ajcn/54.6.997.
• [10] Targeting lactate dehydrogenaseA promotes docetaxelinduced cytotoxicity predominantly in castrationresistant prostate cancer cells.Oncol Rep. 2019 Jul;42(1):224-230. doi: 10.3892/or.2019.7171. Epub 2019 May 24.
• [11] Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis.Sci Rep. 2017 Mar 13;7:44281. doi: 10.1038/srep44281.
• [12] The prognostic value of sarcopenia in patients with surgically treated urothelial carcinoma: A systematic review and meta-analysis.Eur J Surg Oncol. 2019 May;45(5):747-754. doi: 10.1016/j.ejso.2019.03.003. Epub 2019 Mar 7.
• [13] Structural and mechanistic comparison of the Cyclopropane Mycolic Acid Synthases (CMAS) protein family of Mycobacterium tuberculosis.Biochem Biophys Res Commun. 2018 Mar 29;498(2):288-295. doi: 10.1016/j.bbrc.2017.08.119. Epub 2017 Aug 30.
• [14] High pretreatment neutrophil-to-lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: Systematic review and meta-analysis.Head Neck. 2019 May;41(5):1525-1535. doi: 10.1002/hed.25583. Epub 2018 Dec 30.
• [15] Review of the medical literature and assessment of current utilization patterns regarding the use of two common fluorescence in situ hybridization assays in the diagnosis of dermatofibrosarcoma protuberans and clear cell sarcoma.J Cutan Pathol. 2018 Dec;45(12):905-913. doi: 10.1111/cup.13345. Epub 2018 Sep 27.
• [16] Role of wedge resection in bronchial carcinoid (BC) tumors: SEER database analysis.J Thorac Dis. 2019 Apr;11(4):1355-1362. doi: 10.21037/jtd.2019.03.89.
• [17] Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer.Oncotarget. 2017 May 29;8(37):61404-61414. doi: 10.18632/oncotarget.18248. eCollection 2017 Sep 22.
• [18] Disruption of sialic acid metabolism drives tumor growth by augmenting CD8(+) T cell apoptosis.Int J Cancer. 2019 May 1;144(9):2290-2302. doi: 10.1002/ijc.32084. Epub 2019 Jan 3.
• [19] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [20] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [21] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [22] 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.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity. ACS Chem Biol. 2016 Aug 19;11(8):2131-9. doi: 10.1021/acschembio.6b00433. Epub 2016 Jul 22.