Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIV1WSL)

• DOT Name: Ganglioside-induced differentiation-associated protein 2 (GDAP2)
• Gene Name: GDAP2
• Related Disease:
  Cerebellar ataxia
  Spinocerebellar ataxia, autosomal recessive 27
• UniProt ID: GDAP2_HUMAN
• PDB ID: 4UML
• Pfam ID: PF13716 ; PF01661
• Sequence:
  MDPLGAPSQFVDVDTLPSWGDSCQDELNSSDTTAEIFQEDTVRSPFLYNKDVNGKVVLWK
  GDVALLNCTAIVNTSNESLTDKNPVSESIFMLAGPDLKEDLQKLKGCRTGEAKLTKGFNL
  AARFIIHTVGPKYKSRYRTAAESSLYSCYRNVLQLAKEQSMSSVGFCVINSAKRGYPLED
  ATHIALRTVRRFLEIHGETIEKVVFAVSDLEEGTYQKLLPLYFPRSLKEENRSLPYLPAD
  IGNAEGEPVVPERQIRISEKPGAPEDNQEEEDEGLGVDLSFIGSHAFARMEGDIDKQRKL
  ILQGQLSEAALQKQHQRNYNRWLCQARSEDLSDIASLKALYQTGVDNCGRTVMVVVGRNI
  PVTLIDMDKALLYFIHVMDHIAVKEYVLVYFHTLTSEYNHLDSDFLKKLYDVVDVKYKRN
  LKAVYFVHPTFRSKVSTWFFTTFSVSGLKDKIHHVDSLHQLFSAISPEQIDFPPFVLEYD
  ARENGPYYTSYPPSPDL

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[1]
Spinocerebellar ataxia, autosomal recessive 27	DIS2OA53	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[8]
Manganese	DMKT129	Investigative	Manganese increases the expression of Ganglioside-induced differentiation-associated protein 2 (GDAP2).	[9]

References

• [1] GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia. Brain. 2018 Sep 1;141(9):2592-2604. doi: 10.1093/brain/awy198.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.