MAPT
Microtubule-Associated Protein Tau
Gene Number: 4137
Location: 17q21.31
Key Functions: Tau production, microtubule stabilization, nerve-cell structure and intracellular transport
MAPT produces tau, a protein that helps maintain the internal framework of nerve cells. Tau supports microtubules—the structures that help cells retain their shape and transport materials along nerve fibers. Changes in tau function and its accumulation inside brain cells are central to several neurodegenerative diseases [R].
This report examines rs9468, a marker of the common MAPT H1/H2 haplotypes studied in Parkinson’s disease and progressive supranuclear palsy. It also covers rs143624519 (A152T), a separate rare variant associated with susceptibility to certain neurodegenerative conditions, when present in your raw DNA file.
Explore your genotype below, or read about APOE and Alzheimer’s disease susceptibility and BDNF and brain plasticity for other aspects of brain-health genetics.
SNP ID | Your Genotype | Alt Allele | Interpretation |
|---|---|---|---|
rs9468 | Analyze your DNA to see your genotype | C | Analyze your DNA to see a personalized result. |
rs143624519 | Analyze your DNA to see your genotype | A | Analyze your DNA to see a personalized result. |
rs9468 — MAPT Haplotypes and Parkinson’s Disease
TT – H1/H1. Two copies of the H1-associated allele. This common genotype lacks the H2 haplotype linked to lower Parkinson’s disease odds.
CT – H1/H2. One copy of the H2-associated C allele, linked to lower Parkinson’s disease odds [R].
CC — H2/H2. Two copies of the H2-associated C allele, also linked to lower Parkinson’s disease odds. This does not establish twice the protection seen with CT [R].
An Italian study of 904 people with Parkinson’s disease and 891 controls reported approximately 31% lower odds associated with the C allele after adjustment for sex, smoking and coffee consumption [R].
Functional context: rs9468 lies in a noncoding region of MAPT and marks a larger inherited segment called a haplotype. H1 and H2 track differences across this region; rs9468 itself does not change tau’s protein sequence [R].
rs143624519 (A152T)
GG – Common genotype. No copies of the A152T variant. This result does not exclude other genetic influences on dementia risk..
AG – One A152T copy. Linked to increased susceptibility to frontotemporal dementia-spectrum disorders and Alzheimer’s disease in research [R].
AA – Two A152T copies. An exceptionally rare genotype. Available research does not establish a reliable risk estimate specifically for AA [R].
What Have Studies Found?
A 2012 study examining 15,369 people reported that A152T carriers had approximately [R]:
3.0× the odds of frontotemporal dementia-spectrum disorders compared with noncarriers.
2.3× the odds of Alzheimer’s disease.
A later independent study involving 3,100 patients and 4,351 controls supported increased susceptibility to frontotemporal dementia and progressive supranuclear palsy, a condition affecting movement, balance and eye movements [R].
Research has also linked A152T to dementia with Lewy bodies. One study reported an odds ratio of 5.76, although the wide confidence interval (1.62–20.51) reflects uncertainty from the small number of carriers (R).
Functional effect: A152T replaces alanine with threonine in tau. Laboratory experiments found weaker binding to microtubules and increased formation of small tau clusters called oligomers, providing a possible explanation for its influence on disease susceptibility [R].
A152T is studied as a susceptibility variant; carrying it does not mean dementia will develop. An A-containing result from a consumer raw DNA file should be clinically confirmed before informing medical decisions.
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