The TPR (Translocated Promoter Region) gene encodes a structural protein integral to the assembly and function of the nuclear pore complex (NPC), belonging to a gene family characterized by long coiled-coil domains that facilitate protein-protein interactions and the formation of large multimeric complexes. Localized primarily within the nuclear basket region of the NPC, the TPR protein acts as a critical scaffold that maintains the structural stability of the pore, thereby regulating the bidirectional transport of macromolecules between the nucleus and cytoplasm. Beyond its structural role, TPR is involved in diverse cellular processes, including mRNA export, telomere maintenance, and mitotic regulation, where it interacts with key partners such as NUP153 for nucleocytoplasmic transport and MAD1 for spindle assembly checkpoint control. Additionally, TPR participates in DNA damage repair pathways, linking nuclear architecture to genomic integrity. Disruptions in TPR function, such as mutations that destabilize its coiled-coil structure, lead to defective NPC assembly, aberrant nuclear envelope morphology, mRNA retention, and increased genomic instability. The gene is implicated in several pathological conditions; for instance, TPR rearrangements have been associated with thyroid cancer and acute myeloid leukemia, while its loss accelerates cellular senescence. Conversely, altered expression levels disrupt nuclear transport homeostasis, potentially causing mislocalization of tumor suppressors like p53 or mispositioning of nuclear envelope proteins such as SUN1/2, which can induce progeroid phenotypes. Thus, TPR plays a central role in maintaining nuclear structure and signal transduction, and its dysregulation contributes to diseases ranging from cancer to premature aging syndromes through impairments in nucleocytoplasmic transport, telomere maintenance, and DNA repair.
Subcellular localization of TPR (and its protein):
Gene Ontology (GO) terms for TPR:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 3013 RNA transport [PATH:hsa03013] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5216 Thyroid cancer [PATH:hsa05216] |
| Name |
|---|
| Antiviral mechanism by IFN-stimulated genes |
| Cell Cycle |
| Cell Cycle, Mitotic |
| Cellular response to heat stress |
| Cellular responses to stress |
| Cytokine Signaling in Immune system |
| Disease |
| Export of Viral Ribonucleoproteins from Nucleus |
| Gene Expression |
| Glucose transport |
| Hexose transport |
| HIV Infection |
| HIV Life Cycle |
| Host Interactions of HIV factors |
| Infectious disease |
| Influenza Infection |
| Influenza Life Cycle |
| Influenza Viral RNA Transcription and Replication |
| Interactions of Rev with host cellular proteins |
| Interactions of Vpr with host cellular proteins |
| Interferon Signaling |
| ISG15 antiviral mechanism |
| Late Phase of HIV Life Cycle |
| M Phase |
| Metabolism of carbohydrates |
| Metabolism of non-coding RNA |
| Metabolism of proteins |
| Mitotic Prophase |
| NEP/NS2 Interacts with the Cellular Export Machinery |
| Nuclear Envelope Breakdown |
| Nuclear import of Rev protein |
| Nuclear Pore Complex (NPC) Disassembly |
| Post-translational protein modification |
| Processing of Capped Intron-Containing Pre-mRNA |
| Regulation of Glucokinase by Glucokinase Regulatory Protein |
| Regulation of HSF1-mediated heat shock response |
| Regulatory RNA pathways |
| Rev-mediated nuclear export of HIV RNA |
| SLC-mediated transmembrane transport |
| snRNP Assembly |
| SUMO E3 ligases SUMOylate target proteins |
| SUMOylation |
| SUMOylation of DNA damage response and repair proteins |
| Transcriptional regulation by small RNAs |
| Transmembrane transport of small molecules |
| Transport of Mature mRNA derived from an Intron-Containing Transcript |
| Transport of Mature mRNA Derived from an Intronless Transcript |
| Transport of Mature mRNAs Derived from Intronless Transcripts |
| Transport of Mature Transcript to Cytoplasm |
| Transport of Ribonucleoproteins into the Host Nucleus |
| Transport of the SLBP Dependant Mature mRNA |
| Transport of the SLBP independent Mature mRNA |
| Viral Messenger RNA Synthesis |
| Vpr-mediated nuclear import of PICs |
| Disease | Score | NofPmids | NofSnps | Source |
| Papillary thyroid carcinoma | 0.120271442 | 1 | 0 | BeFree_ORPHANET |
| Thyroid Neoplasm | 0.12 | 1 | 0 | CTD_human |
| Ependymoma | 0.00272435 | 1 | 0 | LHGDN |
| Stomach Carcinoma | 0.000542884 | 2 | 0 | BeFree |
| FANCONI ANEMIA, COMPLEMENTATION GROUP A (disorder) | 0.000271442 | 1 | 0 | BeFree |
| Glioblastoma | 0.000271442 | 1 | 0 | BeFree |
| Fanconi Anemia | 0.000271442 | 1 | 0 | BeFree |
| Spastic syndrome | 0.000271442 | 1 | 0 | BeFree |
| PITUITARY ADENOMA PREDISPOSITION (disorder) | 0.000271442 | 1 | 0 | BeFree |
| Metastatic malignant neoplasm to brain | 0.000271442 | 1 | 0 | BeFree |
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