Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5QRKV)

• DOT Name: Kelch repeat and BTB domain-containing protein 13 (KBTBD13)
• Gene Name: KBTBD13
• Related Disease:
  Nemaline myopathy 6
  Childhood-onset nemaline myopathy
  Nemaline myopathy
• UniProt ID: KBTBD_HUMAN
• Pfam ID: PF00651 ; PF01344
• Sequence:
  MARGPQTLVQVWVGGQLFQADRALLVEHCGFFRGLFRSGMRETRAAEVRLGVLSAGGFRA
  TLQVLRGDRPALAAEDELLQAVECAAFLQAPALARFLEHNLTSDNCALLCDAAAAFGLRD
  VFHSAALFICDGERELAAELALPEARAYVAALRPSSYAAVSTHTPAPGFLEDASRTLCYL
  DEEEDAWRTLAALPLEASTLLAGVATLGNKLYIVGGVRGASKEVVELGFCYDPDGGTWHE
  FPSPHQPRYDTALAGFDGRLYAIGGEFQRTPISSVERYDPAAGCWSFVADLPQPAAGVPC
  AQACGRLFVCLWRPADTTAVVEYAVRTDAWLPVAELRRPQSYGHCMVAHRDSLYVVRNGP
  SDDFLHCAIDCLNLATGQWTALPGQFVNSKGALFTAVVRGDTVYTVNRMFTLLYAIEGGT
  WRLLREKAGFPRPGSLQTFLLRLPPGAPGPVTSTTAEL
• Function: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex.
• Tissue Specificity: Expressed in skeletal muscle.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nemaline myopathy 6	DISZ45E1	Definitive	Autosomal dominant	[1]
Childhood-onset nemaline myopathy	DIST7MSL	Supportive	Autosomal dominant	[2]
Nemaline myopathy	DIS5IYLY	Disputed	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Kelch repeat and BTB domain-containing protein 13 (KBTBD13).	[4]

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 Kelch repeat and BTB domain-containing protein 13 (KBTBD13).	[5]

References

• [1] Nemaline myopathy type 6: clinical and myopathological features. Muscle Nerve. 2010 Dec;42(6):901-7. doi: 10.1002/mus.21788.
• [2] Nemaline Myopathy C RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2002 Jun 19 [updated 2015 Jun 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] A family with nemaline myopathy type 6 caused by hseterozygous mutation (c.1222C>T) in the KBTBD13 gene in China: A case report.Neuropathology. 2020 Feb;40(1):104-108. doi: 10.1111/neup.12610. Epub 2019 Dec 11.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.