Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE8T73)

• DTT Name: Wiskott-Aldrich syndrome protein (WAS)
• Synonyms: WASp; IMD2
• Gene Name: WAS
• DTT Type: Clinical trial target; [1]
• UniProt ID: WASP_HUMAN
• TTD ID: T83585
• Sequence:
  MSGGPMGGRPGGRGAPAVQQNIPSTLLQDHENQRLFEMLGRKCLTLATAVVQLYLALPPG
  AEHWTKEHCGAVCFVKDNPQKSYFIRLYGLQAGRLLWEQELYSQLVYSTPTPFFHTFAGD
  DCQAGLNFADEDEAQAFRALVQEKIQKRNQRQSGDRRQLPPPPTPANEERRGGLPPLPLH
  PGGDQGGPPVGPLSLGLATVDIQNPDITSSRYRGLPAPGPSPADKKRSGKKKISKADIGA
  PSGFKHVSHVGWDPQNGFDVNNLDPDLRSLFSRAGISEAQLTDAETSKLIYDFIEDQGGL
  EAVRQEMRRQEPLPPPPPPSRGGNQLPRPPIVGGNKGRSGPLPPVPLGIAPPPPTPRGPP
  PPGRGGPPPPPPPATGRSGPLPPPPPGAGGPPMPPPPPPPPPPPSSGNGPAPPPLPPALV
  PAGGLAPGGGRGALLDQIRQGIQLNKTPGAPESSALQPPPQSSEGLVGALMHVMQKRSRA
  IHSSDEGEDQAGDEDEDDEWDD
• Function: Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria. In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs). Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex.
• KEGG Pathway:
  Chemokine signaling pathway (hsa04062)
  Adherens junction (hsa04520)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Regulation of actin cytoskeleton (hsa04810)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  Generation of second messenger molecules (R-HSA-202433)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OTL-103	DM3BK2Y	Wiskott-Aldrich syndrome	3B62.0	Phase 3	[2]
Hematopoietic stem cell gene therapy	DMQWI7V	Wiskott-Aldrich syndrome	3B62.0	Phase 1/2	[3]
WASP gene therapy	DMN62MP	Wiskott-Aldrich syndrome	3B62.0	Phase 1/2	[1]

References

• [1] ClinicalTrials.gov (NCT01347242) Gene Therapy for Wiskott-Aldrich Syndrome (WAS). U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of Orchard Therapeutics.
• [3] Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther. 2006 Oct;8(5):390-5.