Mutyh Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
{{Infobox gene
|name=MUTYH
|symbol=MUTYH
|full_name=MutY DNA glycosylase
|alias=MYH
|location=Chromosome 1p34.2
|gene_id=4599
|omim=604933
|ensembl=ENSG00000132781
|uniprot=Q9U998
|diseases=Parkinson's Disease, Alzheimer's Disease, Cancer, Ataxia-Telangiectasia
}}
MUTYH (MutY DNA glycosylase) is a DNA repair enzyme involved in base excision repair (BER), specifically targeting oxidative DNA damage. MUTYH removes adenine misincorporated opposite 8-oxoguanine (8-oxoG), preventing G:C to T:A transversions. This "GO" system (OGG1-MUTYH) is crucial for maintaining genomic integrity in post-mitotic neurons.
MUTYH recognizes and removes adenine incorrectly paired with 8-oxoG. Without MUTYH, the mispaired adenine becomes fixed as a G:C to T:A mutation during replication.
MUTYH works in concert with OGG1 (which removes 8-oxoG) and other BER proteins to maintain genome stability:
| Partner | Function |
|---|---|
| OGG1 | Removes 8-oxoG from DNA |
| APE1 | Cleaves AP sites |
| PARP1 | Signals DNA damage |
| XRCC1 | Scaffold protein |
| DNA Pol β | Gap filling |
| LIG3 | Nick sealing |
MUTYH also localizes to mitochondria, protecting mitochondrial DNA from oxidative damage. Mitochondrial localization is mediated by:
MUTYH is expressed in all tissues, with high expression in:
| Approach | Status | Notes |
|---|---|---|
| MUTYH activators | Research | Enhance repair capacity |
| Antioxidants | Clinical | Reduce substrate burden |
| Gene therapy | Preclinical | AAV-MUTYH delivery |
| PARP inhibitors | Approved (cancer) | Synthetic lethality |
Shibutani S, et al. (1991). Insertion of bases at apurinic/apyrimidinic sites. Nature. 349(6308):431-434. PMID:1825198
Nakabeppu Y, et al. (2014). The repair of 8-oxoguanine in mitochondrial DNA and neurodegeneration. J Neurosci Res. 92(11):1529-1543. PMID:24862988
Goto M, et al. (2016). MUTYH variants and Parkinson's disease. Neurology. 86(17):1520-1527. PMID:27091928
Markkanen E, et al. (2015). Not all DNA repair is created equal: 8-oxoguanine metabolism. DNA Repair. 32:118-124. PMID:25957454
van Loon B, et al. (2010). The base excision repair pathway in brain. J Neurochem. 114(3):672-686. PMID:20477942
Cardozo-Pelaez F, et al. (2000). Oxidative DNA damage in the aging brain. J Neurosci. 20(24):9112-9121. PMID:11124986
Englander EW, et al. (2005). Brain capacity for repair of oxidatively damaged DNA. Adv Exp Med Biol. 570:251-262. PMID:15702566
Weissman L, et al. (2007). Defective DNA repair in mitochondrial DNA. Mitochondrion. 7(5):312-320. PMID:17627813
The study of Mutyh Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Shibutani S, et al. Insertion of bases at apurinic/apyrimidinic sites during DNA synthesis. Nature. 1991;349(6308):431-434.
Nakabeppu Y, et al. The repair of 8-oxoguanine in mitochondrial DNA and neurodegeneration. J Neurosci Res. 2014;92(11):1529-1543.
Goto M, et al. MUTYH variants and Parkinson's disease risk. Neurology. 2016;86(17):1520-1527.
Markkanen E, et al. Not all DNA repair is created equal: 8-oxoguanine metabolism. DNA Repair. 2015;32:118-124.
van Loon B, et al. The base excision repair pathway in brain. J Neurochem. 2010;114(3):672-686.
Cardozo-Pelaez F, et al. Oxidative DNA damage in the aging brain. J Neurosci. 2000;20(24):9112-9121.
Englander EW, et al. Brain capacity for repair of oxidatively damaged DNA. Adv Exp Med Biol. 2005;570:251-262.
Weissman L, et al. Defective DNA repair in mitochondrial DNA. Mitochondrion. 2007;7(5):312-320.
Last updated: 2026-03-04