Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK4BXQS)

• DOT Name: Membrane-spanning 4-domains subfamily A member 6A (MS4A6A)
• Synonyms: CD20 antigen-like 3; Four-span transmembrane protein 3
• Gene Name: MS4A6A
• Related Disease:
  IgA nephropathy
  Alzheimer disease
  Parkinson disease
• UniProt ID: M4A6A_HUMAN
• Pfam ID: PF04103
• Sequence:
  MTSQPVPNETIIVLPSNVINFSQAEKPEPTNQGQDSLKKHLHAEIKVIGTIQILCGMMVL
  SLGIILASASFSPNFTQVTSTLLNSAYPFIGPFFFIISGSLSIATEKRLTKLLVHSSLVG
  SILSALSALVGFIILSVKQATLNPASLQCELDKNNIPTRSYVSYFYHDSLYTTDCYTAKA
  SLAGTLSLMLICTLLEFCLAVLTAVLRWKQAYSDFPGSVLFLPHSYIGNSGMSSKMTHDC
  GYEELLTS
• Function: May be involved in signal transduction as a component of a multimeric receptor complex.
• Tissue Specificity: Variable expression in some B-cell, myelomonocytic, and erythroleukemia cell lines.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	moderate	Genetic Variation	[2]
Parkinson disease	DISQVHKL	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[8]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[12]
Taurine	DMVW7N3	Investigative	Taurine decreases the expression of Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[13]

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 Membrane-spanning 4-domains subfamily A member 6A (MS4A6A).	[10]

References

• [1] The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.PLoS One. 2014 Aug 18;9(8):e103413. doi: 10.1371/journal.pone.0103413. eCollection 2014.
• [2] Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.Nat Genet. 2019 Mar;51(3):404-413. doi: 10.1038/s41588-018-0311-9. Epub 2019 Jan 7.
• [3] The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients.Neurosci Lett. 2016 May 16;621:133-136. doi: 10.1016/j.neulet.2016.04.014. Epub 2016 Apr 13.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] 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.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [10] 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.
• [11] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [12] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [13] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.