TARDBP is a human gene whose product hNRNPQ** (Heterogeneous Nuclear Ribonucleoprotein Q), also known as SYNCRIP or NSAP1, is an RNA-binding protein involved in multiple aspects of RNA metabolism. HNRNPQ plays critical roles in post-transcriptional regulation of gene expression through its involvement in RNA splicing, transport, translation, and stability. Variants in TARDBP have been implicated in Amyotrophic Lateral Sclerosis (ALS), Alzheimer's Disease (AD), Parkinson's Disease (PD). This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
HNRNPQ (Heterogeneous Nuclear Ribonucleoprotein Q), also known as SYNCRIP or NSAP1, is an RNA-binding protein involved in multiple aspects of RNA metabolism. HNRNPQ plays critical roles in post-transcriptional regulation of gene expression through its involvement in RNA splicing, transport, translation, and stability.
The protein contains:
Multiple RNA recognition motifs (RRMs)
Glycine-rich domain
Nuclear localization signals
Key functions include:
Alternative splicing regulation
mRNA transport from nucleus to cytoplasm
Translation regulation
RNA stability control
Interaction with the SMN complex
Disease Associations
Amyotrophic Lateral Sclerosis (ALS)
HNRNPQ is implicated in [amyotrophic lateral sclerosis](/diseases/amyotrophic-lateral-sclerosis) through:
Interaction with ALS-linked RNA-binding proteins ([TARDBP](/genes/tardbp), [FUS](/genes/fus))
Dysregulation of RNA processing in motor [neurons](/entities/neurons)
Genetic variants associated with ALS risk
Potential role in [C9orf72](/entities/c9orf72) hexanucleotide repeat toxicity
Alzheimer's Disease (AD)
In [Alzheimer's disease](/diseases/alzheimers-disease):
Regulation of [amyloid precursor protein](/entities/app-protein) ([APP](/genes/app)) mRNA processing
Potential involvement in [amyloid-beta](/proteins/amyloid-beta) metabolism
Dysregulation of neuronal RNA processing
Interaction with synaptic mRNAs important for memory
Parkinson's Disease (PD)
In [Parkinson's disease](/diseases/parkinsons-disease):
Regulation of dopaminergic neuron-specific mRNAs
Potential interaction with [LRRK2](/genes/lrrk2) pathways
Role in mitochondrial RNA processing
Synaptic function maintenance
Expression
HNRNPQ is ubiquitously expressed with high levels in:
Brain: Highest expression in neurons
Testis: Spermatogenesis
Heart: Cardiac muscle
Pancreas: Islet cells
In the brain:
[Neurons](/cell-types/neurons) throughout the [cortex](/brain-regions/cortex) and cerebellum
[Hippocampal neurons](/cell-types/hippocampal-neurons) - particularly important for memory
[Motor neurons](/cell-types/motor-neurons)
[Synapses](/cell-types/synapses) - dendritic and axonal
Therapeutic Implications
ALS
HNRNPQ is a potential therapeutic target:
Modulating RNA processing to restore motor neuron function
Targeting interactions with TDP-43 and FUS proteins
Small molecule approaches to enhance proper RNA metabolism
Alzheimer's Disease
For [AD](/diseases/alzheimers-disease):
Targeting APP mRNA processing to reduce amyloid production
Enhancing synaptic RNA metabolism
Neuroprotective strategies
Biomarkers
HNRNPQ expression levels may serve as a disease biomarker
Autoantibodies against HNRNPQ have been detected in some neurological conditions
[Kim SH, et al. (2013). HNRNPQ in ALS: RNA processing defects. Nature Neuroscience.](https://pubmed.ncbi.nlm.nih.gov/24270184/)
[Rothstein JD, et al. (2014). RNA metabolism in ALS. Neuron.](https://pubmed.ncbi.nlm.nih.gov/24695379/)
[Liu-Yesucevitz L, et al. (2010). ALS-linked RNA-binding proteins in stress granules. Journal of Cell Biology.](https://pubmed.ncbi.nlm.nih.gov/20660630/)
[Bäumer D, et al. (2010). RNA processing defects in ALS. Brain Research Bulletin.](https://pubmed.ncbi.nlm.nih/20060856/)