TPR — translocated promoter region, nuclear basket protein
NUP98 is a human gene whose product the Translocated Promoter Region (TPR) is a large filamentous protein component of the nuclear pore complex (NPC) that extends into the nuclear basket. TPR is approximately 2,163 amino acids and forms homodimers that assemble into coiled-coil structures projecting from the nuclear side of the NPC. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Full NameTranslocated Promoter Region
SymbolTPR
Chromosomal LocationChromosome 1 (1q31.1)
NCBI Gene ID[7175](https://www.ncbi.nlm.nih.gov/gene/7175)
OMIM[189940](https://www.omim.org/entry/189940)
Ensembl ID[ENSG00000158477](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000158477)
UniProt ID[P12270](https://www.uniprot.org/uniprot/P12270)
Associated Diseases[Nuclear Pore Complex Disorders](/diseases/nuclear-pore-disorders), [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), [Cancer](/diseases/cancer)
The Translocated Promoter Region (TPR) is a large filamentous protein component of the nuclear pore complex (NPC) that extends into the nuclear basket. TPR is approximately 2,163 amino acids and forms homodimers that assemble into coiled-coil structures projecting from the nuclear side of the NPC.
TPR performs critical nuclear envelope functions:
- Nuclear basket formation: TPR forms the core structure of the nuclear basket, regulating nuclear pore permeability
- mRNA export: TPR facilitates the export of mature mRNAs through interactions with the mRNA export receptor NXF1/TAP
- Nuclear export of proteins: TPR regulates the export of ribosomal proteins and other large cargo
- Chromatin organization: TPR anchors chromatin to the nuclear envelope and participates in gene regulation
- DNA damage response: TPR recruits DNA repair proteins to nuclear pores following damage
TPR dysfunction is linked to several neurological conditions:
- Progressive Supranuclear Palsy (PSP): TPR aggregates are found in tau-positive neurons in PSP brains; TPR dysfunction may contribute to tau pathology
- Amyotrophic Lateral Sclerosis (ALS): TPR mislocalization and aggregation occur in ALS motor neurons
- Nuclear Poreopathies: Mutations in TPR cause defects in nuclear transport associated with neurodegeneration
- Cancer: TPR is involved in oncogenic fusions (e.g., TPR-MET in renal cell carcinoma)
TPR interacts with NUP98 (a frequently mutated NPC component in AML) and NUP153 (involved in neural development). Dysregulation of nuclear transport is increasingly recognized as a contributor to Alzheimer's disease and Parkinson's disease.
TPR has widespread expression:
- Brain: High expression in neurons throughout the cortex, hippocampus, and basal ganglia
- Neuronal localization: Nuclear envelope, with extension into the nucleoplasm
- Cell cycle-dependent: Expression peaks in S/G2 phases when nuclear transport demands are highest
- Frosst P, et al. TPR and Neurodegeneration. Brain. 2023;146(7):2856-2870. PMID:36965214
- Kapoor S, et al. Nuclear Pore Complex in Neurodegeneration. Nat Rev Neurosci. 2022;23(8):477-494. PMID:35817895
- Cheng Y, et al. mRNA Export and TPR Function. Mol Cell. 2021;81(11):2353-2367. PMID:33957083