USP34 Gene: Function, Mutations, and Disease Associations | NCBI, UniProt

USP34 (Ubiquitin Specific Peptidase 34) encodes a deubiquitinating enzyme that removes ubiquitin from specific protein substrates. It plays critical roles in DNA damage repair, Wnt/β-catenin signaling, and regulation of protein stability. USP34 is involved in cellular processes such as cell cycle progression, apoptosis, and transcriptional regulation. Dysregulation of USP34 has been implicated in various cancers and developmental disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Wnt/β-catenin signaling pathway

• DNA damage response (DDR)

• Ubiquitin-proteasome pathway

USP34 is a 3,546-amino acid deubiquitinating enzyme (DUB) belonging to the ubiquitin-specific protease family. It contains a catalytic USP domain and multiple ubiquitin-interacting motifs. USP34 removes ubiquitin chains from substrates such as AXIN, p53, and RNF168, thereby regulating protein stability and signaling. It is predominantly nuclear and cytoplasmic, with highest expression in testis and brain. USP34 is essential for DNA double-strand break repair via homologous recombination and modulates Wnt signaling by stabilizing AXIN, a negative regulator of β-catenin. Alterations in USP34 expression or function contribute to cancer progression and neurodevelopmental phenotypes.