Meyahealth
Home
ENES
HomeGeneticsGeneTARDBP gene
Back to Gene

TARDBP gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TARDBP gene

The TARDBP gene provides instructions for making the TDP-43 protein, which regulates gene expression and protein production, particularly in the nervous system.

Normal Function

The TARDBP gene provides instructions for making a protein called transactive response DNA binding protein 43 kDa (TDP-43). This protein is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. The TDP-43 protein attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. This protein can also bind to RNA to ensure the RNA's stability.

The TDP-43 protein is involved in processing molecules called messenger RNA (mRNA), which serve as the genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the TDP-43 protein controls the production of different versions of certain proteins, a process known as alternative splicing. The TARDBP gene is particularly active during early development before birth, and many of the proteins influenced by TDP-43 are involved in nervous system and organ development.

Health Conditions Related to Genetic Changes

Amyotrophic lateral sclerosis

At least 60 mutations in the TARDBP gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive muscle weakness, a loss of muscle mass, and an inability to control movement.

  • Mechanism: Most mutations change single amino acids in the TDP-43 protein, often affecting the region involved in mRNA processing.
  • Protein Aggregates: Changes to the TDP-43 protein cause it to misfold and form protein clumps (aggregates), which have been found in motor neurons in some people with ALS.
  • ALS-FTD: Some people with ALS caused by TARDBP mutations also develop frontotemporal dementia (FTD), a progressive brain disorder affecting personality, behavior, and language. Individuals with both are diagnosed with ALS-FTD.

Other disorders

Mutations in the TARDBP gene have been found to cause frontotemporal dementia (FTD) without features of ALS. This is characterized by a gradual loss of problem-solving skills and language comprehension, as well as changes in personality and behavior. Because these mutations often leave parts of the protein functional, symptoms tend to appear later in life, in one's late sixties or early seventies. Some individuals who inherit the altered gene never develop FTD, a situation known as reduced penetrance.

Other Names for This Gene

  • ALS10
  • TADBP_HUMAN
  • TAR DNA-binding protein 43
  • TAR DNA-binding protein-43
  • TDP-43

Frequently Asked Questions

The initial symptoms of ALS caused by TARDBP gene mutations are similar to other forms of ALS and typically involve progressive muscle weakness. This can manifest as subtle changes like tripping, difficulty grasping objects, slurred speech (dysarthria), or muscle twitching (fasciculations). The weakness usually progresses, leading to loss of muscle mass and an inability to control voluntary movements, often starting in the limbs or bulbar region (affecting speech, swallowing, and breathing).
Yes, ALS caused by TARDBP gene mutations is often inherited, typically in an autosomal dominant pattern. This means that if a parent has a TARDBP mutation, each child has a 50% chance of inheriting the mutation and potentially developing ALS. Genetic counseling is highly recommended for affected individuals and their family members to understand the inheritance pattern, risks, and testing options.
Some individuals with TARDBP gene mutations develop both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a condition known as ALS-FTD. The TDP-43 protein, encoded by the TARDBP gene, is found to misfold and aggregate in the brain and spinal cord of many people with both ALS and FTD, suggesting a shared underlying pathology. This connection highlights the spectrum of neurodegenerative disorders linked to TDP-43 dysfunction.
Currently, there are no specific treatments that directly target TARDBP gene mutations or the TDP-43 protein aggregates in ALS. Management focuses on symptomatic relief and supportive care, including medications to slow disease progression (e.g., riluzole, edaravone), physical and occupational therapy, speech therapy, and respiratory support. Clinical trials are ongoing to investigate new therapies, including those that might target the underlying genetic or protein mechanisms.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.