TARDBP rs80356734: What Your Genotype Means
The rs80356734 variant is a specific genetic change located within the TARDBP gene. It is clinically associated with Amyotrophic lateral sclerosis type 10, a neurodegenerative condition.
What each genotype means
Typical genetic profile
This is the common, non-pathogenic genotype for this position in the TARDBP gene. It is considered the reference sequence and is not associated with the increased risk of Amyotrophic lateral sclerosis type 10 linked to this variant.
This is the most common genotype found in the general population.
Increased risk profile
This genotype includes one copy of the pathogenic variant associated with Amyotrophic lateral sclerosis type 10. Because this condition follows an autosomal dominant inheritance pattern, the presence of this variant may indicate a higher susceptibility to the disease, though clinical expression can vary significantly between individuals.
This genotype is extremely rare in the general population.
Increased risk profile
This genotype includes two copies of the pathogenic variant associated with Amyotrophic lateral sclerosis type 10. Research identifies this specific change as pathogenic, and individuals with this genotype should consult with a medical geneticist or neurologist to discuss the implications for their health.
This genotype is extremely rare in the general population.
Understanding the Variant
The variant rs80356734 is a single nucleotide polymorphism (SNP) located on chromosome 1 at position 11,022,464. In genetic databases, this variant is specifically linked to the TARDBP gene. A SNP represents a variation at a single position in the DNA sequence among individuals. While most SNPs have no effect on health, some are located in regions that alter protein function or regulation. In the case of rs80356734, clinical databases such as ClinVar have classified this specific change as pathogenic, meaning it is associated with an increased risk for developing certain health conditions. It is important to note that the presence of a pathogenic variant does not guarantee the development of a disease, but rather indicates a documented statistical association observed in clinical research studies.
The Role of the TARDBP Gene
The TARDBP gene provides the instructions for the body to produce a protein known as transactive response DNA binding protein 43 kDa, or TDP-43. This protein is found in the nucleus of most cells and plays a critical role in the regulation of gene expression, specifically in the processing of RNA. By binding to DNA and RNA, TDP-43 ensures the stability of genetic messages and influences how proteins are synthesized. This gene is particularly active during early development, helping to form the nervous system. When mutations occur in TARDBP, they can lead to the production of misfolded TDP-43 protein. These misfolded proteins may clump together, forming aggregates within nerve cells. Researchers are currently investigating whether these aggregates directly cause the death of motor neurons or if they are a secondary effect of cellular stress in neurodegenerative conditions.
Clinical Associations and Evidence
Research has established a link between specific variants in the TARDBP gene and Amyotrophic lateral sclerosis (ALS), specifically type 10. ALS is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness and loss of movement. The evidence for the pathogenicity of variants in this gene is supported by clinical observations of families with inherited forms of the disease. While TARDBP mutations are a known cause of ALS, they account for a small percentage of total cases—roughly 3% to 5% of familial ALS cases and less than 1% of sporadic cases. The clinical presentation can be highly variable, even among individuals carrying the same genetic variant, with symptoms ranging from muscle weakness to cognitive changes associated with frontotemporal dementia. Because of this variability, clinical diagnosis relies on a combination of genetic testing and neurological evaluation.
Population Frequency
Information regarding the population frequency of the rs80356734 variant is limited in public databases. It is not commonly reported as a high-frequency variant in the general population, which is consistent with its classification as a pathogenic variant associated with a rare, serious condition. Because it is not a common polymorphism, it is not typically included in standard ancestry-based genetic screening panels. If you have received information about this variant from a clinical test, it is essential to discuss the findings with a genetic counselor or a medical specialist who can interpret the results within the context of your personal and family medical history.
Navigating Genetic Information
If you are concerned about your genetic risk for ALS or other neurodegenerative conditions, it is important to understand what you can and cannot do with this information. Genetic testing for specific variants like rs80356734 should always be performed in a clinical setting, such as through a neurologist or a certified genetic counselor, rather than through direct-to-consumer testing kits. These professionals can provide context, explain the limitations of the test, and discuss the implications for you and your family members. There is currently no cure for TARDBP-related ALS, but multidisciplinary supportive care is available to manage symptoms and improve quality of life. Never make medical decisions based solely on a genetic report; always consult with a healthcare provider to determine if further diagnostic testing or surveillance is appropriate for your specific situation.
How common is this variant?
The rs80356734 variant is rare in the general population, and specific frequency data across different ancestral groups is not currently recorded in major public databases.
Frequently asked questions
What is Amyotrophic lateral sclerosis type 10?
Amyotrophic lateral sclerosis type 10 is a specific form of ALS caused by pathogenic variants in the TARDBP gene. It is characterized by the progressive degeneration of motor neurons, leading to muscle weakness and movement difficulties.
Does having a TARDBP variant mean I will get ALS?
Not necessarily. While certain variants are associated with an increased risk of ALS, genetic predisposition is complex. You should consult with a neurologist or genetic counselor to understand your specific risk factors.
Is there a cure for TARDBP-related ALS?
Currently, there is no cure for TARDBP-related ALS. Treatment focuses on multidisciplinary supportive care to manage symptoms, maintain function, and improve the quality of life for patients.
Should I get tested for the rs80356734 variant?
Genetic testing for specific disease-associated variants should be discussed with a healthcare professional. They can determine if testing is clinically indicated based on your family history and symptoms.
Sources & further reading
Educational information only, last refreshed 9/29/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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