Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR61MI8)

• DOT Name: Kappa-casein (CSN3)
• Gene Name: CSN3
• Related Disease:
  Carcinoma
  Multiple sclerosis
  Bone osteosarcoma
  Cardiovascular disease
  Hepatocellular carcinoma
  Liver cirrhosis
  Neoplasm
  Osteosarcoma
  Ankylosing spondylitis
  Undifferentiated carcinoma
  Fish eye disease
• UniProt ID: CASK_HUMAN
• Pfam ID: PF00997
• Sequence:
  MKSFLLVVNALALTLPFLAVEVQNQKQPACHENDERPFYQKTAPYVPMYYVPNSYPYYGT
  NLYQRRPAIAINNPYVPRTYYANPAVVRPHAQIPQRQYLPNSHPPTVVRRPNLHPSFIAI
  PPKKIQDKIIIPTINTIATVEPTPAPATEPTVDSVVTPEAFSESIITSTPETTTVAVTPP
  TA
• Function: Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk.
• Tissue Specificity: Mammary gland specific. Secreted in milk.
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Altered Expression	[2]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[3]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[3]
Ankylosing spondylitis	DISRC6IR	moderate	Biomarker	[5]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[1]
Fish eye disease	DISYTZNQ	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kappa-casein (CSN3).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Kappa-casein (CSN3).	[8]

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 decreases the methylation of Kappa-casein (CSN3).	[9]

References

• [1] Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
• [2] Increased transcriptional activity of milk-related genes following the active phase of experimental autoimmune encephalomyelitis and multiple sclerosis.J Immunol. 2007 Sep 15;179(6):4074-82. doi: 10.4049/jimmunol.179.6.4074.
• [3] Inhibition of Csn3 expression induces growth arrest and apoptosis of hepatocellular carcinoma cells.Cancer Chemother Pharmacol. 2012 May;69(5):1173-80. doi: 10.1007/s00280-011-1810-x. Epub 2012 Jan 12.
• [4] Single-nucleotide polymorphisms in vascular Ca2+-activated K+-channel genes and cardiovascular disease.Pflugers Arch. 2010 Jul;460(2):343-51. doi: 10.1007/s00424-009-0768-6. Epub 2009 Dec 31.
• [5] Absence of polymorphism between HLA-B27 genomic exon sequences isolated from normal donors and ankylosing spondylitis patients.J Immunol. 1986 Oct 1;137(7):2168-72.
• [6] Tumor-protective and tumor-promoting actions of dietary whey proteins in an N-methyl-N-nitrosourea model of rat mammary carcinogenesis.Nutr Cancer. 2006;55(2):171-7. doi: 10.1207/s15327914nc5502_8.
• [7] 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.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] 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.