TARDBP Gene: TAR DNA-Binding Protein 43 (TDP-43)
A key gene in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), encoding the TDP-43 protein involved in RNA metabolism and neurodegeneration.
Gene Information Card
| Symbol | TARDBP |
|---|---|
| Full Name | TAR DNA binding protein |
| Gene Type | protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 23435 ncbi.nlm.nih.gov/gene/23435 |
| Ensembl ID | ENSG00000120948 |
| UniProt ID | Q13148 |
| OMIM ID | 605078 |
| HGNC ID | 11571 |
| Aliases | TDP-43, ALS10, TDP43 |
Description
The TARDBP gene encodes TAR DNA-binding protein 43 (TDP-43), a highly conserved nuclear protein involved in RNA transcription, splicing, transport, and translation. TDP-43 is predominantly nuclear but shuttles to the cytoplasm. Mutations in TARDBP are a major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), characterized by cytoplasmic mislocalization and aggregation of TDP-43. TDP-43 pathology is also found in other neurodegenerative disorders, including Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Autosomal dominant mutations cause toxic gain-of-function and loss of nuclear function, leading to neurodegeneration. | ClinVar, OMIM, multiple studies |
| Frontotemporal Dementia (FTD) | Mutations lead to TDP-43 proteinopathy with cytoplasmic inclusions and impaired RNA processing. | ClinVar, OMIM |
| Frontotemporal Lobar Degeneration (FTLD-TDP) | TDP-43 pathology is a hallmark; mutations are rare but cause disease. | OMIM, literature |
| Alzheimer's Disease (AD) | TDP-43 pathology is present in a subset of AD cases, contributing to cognitive decline. | Literature, not primary genetic cause |
| Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) | TDP-43 proteinopathy in the limbic system, often without TARDBP mutations. | Literature, neuropathological diagnosis |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Ubiquitous, highest in neurons |
| Spinal Cord | High | Motor neurons affected in ALS |
| Lung | Medium | Moderate expression |
| Kidney | Medium | Moderate expression |
| Liver | Low | Low expression |
| Heart | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal model, used for TDP-43 studies |
| HeLa (cervical carcinoma) | Medium | Common cell line, endogenous expression |
| HEK293 (embryonic kidney) | Medium | Used for overexpression studies |
| U2OS (osteosarcoma) | Medium | Used in stress granule studies |
| A549 (lung carcinoma) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| A315T | Missense | Rare (found in familial ALS) | Cytoplasmic mislocalization, aggregation, toxicity |
| M337V | Missense | Rare (familial ALS) | Increased aggregation, impaired splicing |
| G298S | Missense | Rare (familial ALS) | Cytoplasmic inclusions, neurotoxicity |
| D169G | Missense | Rare (familial ALS) | Altered RNA binding, aggregation |
| Q331K | Missense | Rare (familial ALS) | Cytoplasmic mislocalization, toxicity |
| N352S | Missense | Rare (familial ALS) | Aggregation, loss of nuclear function |
Mutation functional classification
Loss of Function (LOF)
Loss of nuclear TDP-43 function leads to splicing defects, altered gene expression, and impaired RNA metabolism, contributing to neurodegeneration.
Gain of Function (GOF)
Mutant TDP-43 forms cytoplasmic aggregates that sequester RNA and proteins, causing toxicity and impairing cellular processes.
Dominant Negative (DN)
Mutant TDP-43 can interfere with wild-type TDP-43 function, exacerbating loss of normal activity.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • RNA binding |
| • mRNA splicing | • regulation of transcription |
| • protein homodimerization | • cytoplasmic stress granule |
| • nucleus | • cytoplasm |
| • mRNA transport | • negative regulation of gene expression |
Pathways
• RNA splicing
• mRNA surveillance
• Amyotrophic lateral sclerosis (ALS) pathway
• Frontotemporal dementia (FTD) pathway
• TDP-43 proteinopathy pathway
Protein Summary
TDP-43 is a 414-amino acid protein with two RNA recognition motifs (RRM1 and RRM2) and a glycine-rich C-terminal domain. It is involved in RNA processing, including splicing, transport, and translation. Under pathological conditions, TDP-43 is cleaved, hyperphosphorylated, and ubiquitinated, leading to cytoplasmic aggregates. These aggregates are a hallmark of ALS and FTD. The protein is essential for normal neuronal function, and its dysfunction is central to neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TARDBP Knockout HEK293 Cell Line | EDJ-KQ17905 | Human | 23435 | Details Get a Quote |
| TARDBP Knockout HeLa Cell Line | EDJ-KQ55738 | Human | 23435 | Details Get a Quote |
| TARDBP Knockout A-549 Cell Line | EDJ-KQ64236 | Human | 23435 | Details Get a Quote |
| TARDBP Knockout HCT 116 Cell Line | EDJ-KQ72681 | Human | 23435 | Details Get a Quote |
| TARDBP Knockout HAP1 Cell Line | EDJ-KQ78120 | Human | 23435 | Details Get a Quote |
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