TP53INP1 Gene: Function, Expression, Mutations & Disease Associations

TP53INP1 (Tumor Protein p53 Inducible Nuclear Protein 1) is a stress-responsive gene directly regulated by p53. It encodes two splice variants (TP53INP1α and TP53INP1β) that localize to the nucleus and play critical roles in p53-mediated apoptosis, cell cycle arrest, and autophagy. TP53INP1 is induced by various cellular stresses including DNA damage, oxidative stress, and oncogene activation. It functions as a tumor suppressor by promoting p53 transcriptional activity and by modulating autophagy through interaction with LC3 and other autophagic proteins. Downregulation of TP53INP1 is observed in multiple cancers and correlates with poor prognosis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• p53 signaling pathway (KEGG: hsa04115)

• Autophagy - animal (KEGG: hsa04140)

• Apoptosis (KEGG: hsa04210)

• Cellular senescence (KEGG: hsa04218)

• p53-dependent G1 DNA damage response (Reactome: R-HSA-69541)

TP53INP1 is a 27 kDa nuclear protein (isoform α) and 30 kDa protein (isoform β) encoded by the TP53INP1 gene. It contains a p53-binding domain and a LC3-interacting region (LIR) motif, enabling it to regulate both p53 transcriptional activity and autophagy. Under stress conditions, TP53INP1 is induced by p53 and translocates to the nucleus where it enhances p53-mediated transcription of pro-apoptotic genes (e.g., BAX, PUMA). In the cytoplasm, TP53INP1 interacts with LC3 to promote autophagosome formation and autophagic flux. The protein also interacts with stathmin (STMN1) to regulate microtubule dynamics. TP53INP1 is frequently downregulated in cancers through promoter hypermethylation or microRNA-mediated repression, contributing to tumor progression and therapy resistance.