| Symbol
| TARDBP
| contributors: shn/mct - updated : 12-01-2022
|
| HGNC name
| TAR DNA binding protein
|
| HGNC id
| 11571
|
| corresponding disease(s)
|
ALS10
|
| Other morbid association(s)
|
| Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
|
|---|
| constitutional
|
|
| --other
|
|
component of cytoplasmic inclusions in frontotemporal degeneration and amyotrophic lateral sclerosis (aggregation of TARDBP C-terminal fragments, found in cytoplasmic inclusions is regulated by phosphorylation events and both the autophagy and proteasome-mediated degradation pathways)  | | constitutional
|
|
| --over
|
| |
enhancing exon 7 inclusion during the survival of motor neuron pre-mRNA splicing | | constitutional
|
|
|
| loss of function
| |
may induce neuronal degeneration probably through dysregulation of Rho family GTPases | | constitutional
|
|
|
| gain of function
| |
in motor neurons of sporadic ALS patients | | constitutional
|
|
|
| gain of function
| |
in some FTLD-U patients | | constitutional
|
|
| --other
|
| |
inclusions have been found in Alzheimer's disease (AD) cases, most often in a limbic distribution, with or without hippocampal sclerosis | |
| Susceptibility
|
to sporadic amyotrophic lateral sclerosis to Ewing sarcoma |
| Variant & Polymorphism
SNP
, other
| P363A and A382P missense mutations may predispose to ALS in approximately 2 p100 of the individuals |
|
rs9430161 associated with susceptibility to Ewing sarcoma |
| 
|
Candidate gene
Marker
| Therapy target
| | |
|
| System | Type | Disorder | Pubmed |
|---|
| neuromuscular | laterale amyotrophy sclerosis | | |
| TARDBP–ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TARDBP proteinopathies | | neuromuscular | neuropathy | | |
| TARDBP–ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TARDBP proteinopathies | | neurology | neurodegenerative | | |
| reduced insulin/IGF-1 signaling could ameliorate TARDBP toxicity by decreasing its aggregation in neurons | | neurology | neurodegenerative | | |
| targeting of TARDBP mitochondrial localization is a promising therapeutic approach for neurodegeneration |
| | |
|
| postnatal deletion of Tardbp in mice caused dramatic loss of body fat followed by rapid death | |
aberrant Tdp-43- and FUS/TLS-positive nuclear inclusions, abnormal accumulation of mitochondria in motor neurons, immature neuromuscular junctions, and atrophy of skeletal muscle in Tdp-43 mice |
|
In SH-SY5Y human neuroblastoma cells, knockdown of TDP-43 caused altered splicing of about 200 transcripts ( |
|
autophagy activation is an effective route for therapy of Tdp-43 Tg mice with FTLD-U phenotypes |