ALS Gene Library

TARDBP

TAR DNA-Binding Protein

Pathogenic variants in TARDBP are an established cause of ALS.

The gene encodes TDP-43, a protein deeply involved in ALS biology.

TDP-43 pathology is also found in many ALS cases that are not caused by TARDBP mutations.

Sources: Amyotrophic Lateral Sclerosis Overview · Evidence-Based Consensus Guidelines for ALS Genetic Testing and Counseling · Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy

Associated conditions

  • ALS
  • ALS-FTD spectrum in some families

Sources: Amyotrophic Lateral Sclerosis Overview

ALS / FTD relationship

TARDBP is associated primarily with ALS, although ALS-FTD spectrum presentations can occur in some families.

Sources: Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy · Amyotrophic Lateral Sclerosis Overview

Typical inheritance pattern

Typically autosomal dominant.

Sources: Amyotrophic Lateral Sclerosis Overview

Penetrance

Penetrance is variant-dependent and incompletely characterized.

Universal estimates should be avoided.

Sources: Amyotrophic Lateral Sclerosis Overview

Clinical presentation

TARDBP-associated ALS can vary in age of onset and clinical features. The presence of TDP-43 pathology in ALS does not by itself establish a TARDBP mutation.

Sources: Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy · Amyotrophic Lateral Sclerosis Overview

Genetic testing considerations

TARDBP is included among the minimum recommended ALS genes for testing.

Results require variant-level interpretation and clinical context.

Sources: Evidence-Based Consensus Guidelines for ALS Genetic Testing and Counseling

Biomarkers

TDP-43 pathology is important to ALS biology, but it should not be treated as a stand-alone genetic test or as a validated predictor of an individual course. Biomarkers for TDP-43 dysfunction remain an active research area.

Sources: Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy

Available treatments

There is currently no FDA-approved therapy specifically targeting a TARDBP mutation.

Sources: Amyotrophic Lateral Sclerosis Overview

Clinical trials

Search TARDBP ALS studies

Sources: ClinicalTrials.gov: Amyotrophic Lateral Sclerosis studies

Presymptomatic research

Presymptomatic research may be available for selected families or variants. Eligibility should be checked directly with the study team and current registry record.

Search TARDBP studies on ClinicalTrials.gov

Sources: ClinicalTrials.gov: Amyotrophic Lateral Sclerosis studies

Current research

Current research includes TDP-43 biology, variant-specific mechanisms, and approaches aimed at modifying disease pathways.

Sources: Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy

Key research institutions / studies

ClinicalTrials.gov provides the current registry for locating TARDBP-related studies; availability and eligibility change over time.

Open the TARDBP study registry

Sources: ClinicalTrials.gov: Amyotrophic Lateral Sclerosis studies

Sources & Further Reading

These source cards link directly to the original material. External websites open in a new tab.

This information is for education and does not replace individualized medical advice, genetic counseling, diagnosis, or treatment. Genetic risk, penetrance, and testing implications can differ by gene, variant, family, and individual.

Last reviewed: 09-30-2026

Medical information should be reviewed periodically as genetic research and clinical trials change.

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