Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK1L8VX)

• DOT Name: Kyphoscoliosis peptidase (KY)
• Synonyms: EC 3.4.-.-
• Gene Name: KY
• Related Disease:
  Hereditary spastic paraplegia
  Myofibrillar myopathy 7
  Myopathy
  Neuromuscular disease
  Congenital myopathy
  Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome
  Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome
• UniProt ID: KY_HUMAN
• EC Number: 3.4.-.-
• Pfam ID: PF01841
• Sequence:
  MELKKDINAVSIDMLLIVHSEKRRAAQGTLSDQQANPSSLLQRGGGFQGVGNGVRRWQKL
  EGNDFHENLVEKQHPQQPQVITSYNSQGTQLTVEVHPRDAMPQLLKKFSLAKRLQGDKNG
  NTRPRQPGGKDAHAYPWDRSSLKSMSLDLQQFEKLDIYASQVTAKSGLDELVSDLLQEAH
  TDLERVRAIWIWICHHIEYDIAAAQEKDRQAFKPTDILRTQKTNCDGYAGLFERMCRLAG
  VQCMTVPGYSKGFGYQTGQSFSGEFDHAWNAVYLEGRWHLVDSTWGSGLVDTITSKFTFL
  YNEFYFLTHPALFIEDHFPDNKNWQLLKPPQSLRQFENNMYHKSEFYNKGMLSAHPETSM
  IRTVNGKATVTIESCAPTLFMFMLNGKQEHGLLSLRKNGMKLEVYPPTMGTHKLQIFAKG
  NSDIYSSVLEYTLKCNYVDMGVQLPAELHQPVGPSWFSEQMGIMKPSHPDPIIHTSDGRC
  SISFSVEEGINVLASLHGDDGPITEETQRRYIFQLHREKQTELKVQLPHAGKFALKIFVK
  KRQEPGNYIFVFNYLVCCANTKVNWPMFPESFGNWGQDNELLEPLSGVLPANRNVPFKLK
  LHGIAKVLVKGQDTWPLTLNHEGYWEGSCSTAGCQEVYVMVLENANHNFYSYILKYKVNA
  Q
• Function: Probable cytoskeleton-associated protease required for normal muscle growth. Involved in function, maturation and stabilization of the neuromuscular junction. May act by cleaving muscle-specific proteins such as FLNC.
• Tissue Specificity: Highly expressed in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary spastic paraplegia	DISGZQV1	Strong	CausalMutation	[1]
Myofibrillar myopathy 7	DISY3XHI	Strong	Autosomal recessive	[2]
Myopathy	DISOWG27	Strong	Biomarker	[3]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[4]
Congenital myopathy	DISLSK9G	moderate	Biomarker	[5]
Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome	DISCJZO8	Supportive	Autosomal recessive	[1]
Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome	DISNX3L0	Supportive	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Kyphoscoliosis peptidase (KY).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Kyphoscoliosis peptidase (KY).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kyphoscoliosis peptidase (KY).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Kyphoscoliosis peptidase (KY).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Kyphoscoliosis peptidase (KY).	[9]

References

• [1] Progressive hereditary spastic paraplegia caused by a homozygous KY mutation. Eur J Hum Genet. 2017 Aug;25(8):966-972. doi: 10.1038/ejhg.2017.85. Epub 2017 May 10.
• [2] The kyphoscoliosis (ky) mouse is deficient in hypertrophic responses and is caused by a mutation in a novel muscle-specific protein. Hum Mol Genet. 2001 Jan 1;10(1):9-16. doi: 10.1093/hmg/10.1.9.
• [3] Transcriptional upregulation of Bag3, a chaperone-assisted selective autophagy factor, in animal models of KY-deficient hereditary myopathy.Dis Model Mech. 2018 Jul 6;11(7):dmm033225. doi: 10.1242/dmm.033225.
• [4] A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency.Eur J Hum Genet. 2016 Dec;24(12):1771-1777. doi: 10.1038/ejhg.2016.98. Epub 2016 Aug 3.
• [5] Kyphoscoliosis peptidase (KY) mutation causes a novel congenital myopathy with core targetoid defects. Acta Neuropathol. 2016 Sep;132(3):475-8. doi: 10.1007/s00401-016-1602-9. Epub 2016 Aug 2.
• [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] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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.
• [10] 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.