Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJQJ2TZ)

• DOT Name: Peroxisomal membrane protein PEX16 (PEX16)
• Synonyms: Peroxin-16; Peroxisomal biogenesis factor 16
• Gene Name: PEX16
• Related Disease:
  GM1 gangliosidosis
  Non-insulin dependent diabetes
  Peroxisome biogenesis disorder
  Peroxisome biogenesis disorder 8A (Zellweger)
  Peroxisome biogenesis disorder 8B
  African trypanosomiasis
  Osteoarthritis
  Zellweger spectrum disorders
• UniProt ID: PEX16_HUMAN
• Pfam ID: PF08610
• Sequence:
  MEKLRLLGLRYQEYVTRHPAATAQLETAVRGFSYLLAGRFADSHELSELVYSASNLLVLL
  NDGILRKELRKKLPVSLSQQKLLTWLSVLECVEVFMEMGAAKVWGEVGRWLVIALVQLAK
  AVLRMLLLLWFKAGLQTSPPIVPLDRETQAQPPDGDHSPGNHEQSYVGKRSNRVVRTLQN
  TPSLHSRHWGAPQQREGRQQQHHEELSATPTPLGLQETIAEFLYIARPLLHLLSLGLWGQ
  RSWKPWLLAGVVDVTSLSLLSDRKGLTRRERRELRRRTILLLYYLLRSPFYDRFSEARIL
  FLLQLLADHVPGVGLVTRPLMDYLPTWQKIYFYSWG
• Function: Required for peroxisome membrane biogenesis. May play a role in early stages of peroxisome assembly. Can recruit other peroxisomal proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from the endoplasmic reticulum (ER). May function as receptor for PEX3.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway: Class I peroxisomal membrane protein import (R-HSA-9603798)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
GM1 gangliosidosis	DISN3L2M	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[2]
Peroxisome biogenesis disorder	DISBQ6QJ	Definitive	Autosomal recessive	[3]
Peroxisome biogenesis disorder 8A (Zellweger)	DIS3UHXM	Definitive	Autosomal recessive	[4]
Peroxisome biogenesis disorder 8B	DISTHTQ3	Definitive	Autosomal recessive	[4]
African trypanosomiasis	DISBIXK4	Strong	Biomarker	[5]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[6]
Zellweger spectrum disorders	DISW52CE	Supportive	Autosomal recessive	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Peroxisomal membrane protein PEX16 (PEX16).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Peroxisomal membrane protein PEX16 (PEX16).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Peroxisomal membrane protein PEX16 (PEX16).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Peroxisomal membrane protein PEX16 (PEX16).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peroxisomal membrane protein PEX16 (PEX16).	[12]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Peroxisomal membrane protein PEX16 (PEX16).	[13]

References

• [1] Defining the genetic basis of early onset hereditary spastic paraplegia using whole genome sequencing.Neurogenetics. 2016 Oct;17(4):265-270. doi: 10.1007/s10048-016-0495-z. Epub 2016 Sep 28.
• [2] Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits.Psychosom Med. 2018 Apr;80(3):242-251. doi: 10.1097/PSY.0000000000000555.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [5] Identification and functional characterization of Trypanosoma brucei peroxin 16.Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2326-37. doi: 10.1016/j.bbamcr.2015.05.024. Epub 2015 May 27.
• [6] Peroxisomal dysfunction is associated with up-regulation of apoptotic cell death via miR-223 induction in knee osteoarthritis patients with type 2 diabetes mellitus.Bone. 2014 Jul;64:124-31. doi: 10.1016/j.bone.2014.04.001. Epub 2014 Apr 13.
• [7] Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. 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.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.