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.
Overview
Mermaid diagram (expand to render)
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.
Gene and Protein Structure
Gene Organization
Chromosomal location: 1p34.2
Genomic size: ~11.5 kb
Exons: 16 exons
mRNA: 2.5 kb transcript
Protein Features
Molecular weight: ~52 kDa
Amino acids: 479
Active site: Helicase-loop-excision (HLE) motif
Iron-sulfur cluster: 4Fe-4S for DNA binding
Domains:
N-terminal DNA binding domain
Catalytic glycosylase domain
C-terminal disordered region
Function
GO Repair Pathway
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.
Small molecule activators: Development of MUTYH enhancers
Biomarkers: DNA repair capacity as disease marker
Gene therapy: Viral vector delivery to brain
Combination therapies: DNA repair + antioxidant
Key Publications
Shibutani S, et al. (1991). Insertion of bases at apurinic/apyrimidinic sites. Nature. 349(6308):431-434. PMID: 1825198(https://pubmed.ncbi.nlm.nih.gov/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(https://pubmed.ncbi.nlm.nih.gov/24862988/)
Goto M, et al. (2016). MUTYH variants and Parkinson's disease. Neurology. 86(17):1520-1527. PMID: 27091928(https://pubmed.ncbi.nlm.nih.gov/27091928/)
Markkanen E, et al. (2015). Not all DNA repair is created equal: 8-oxoguanine metabolism. DNA Repair. 32:118-124. PMID: 25957454(https://pubmed.ncbi.nlm.nih.gov/25957454/)
van Loon B, et al. (2010). The base excision repair pathway in brain. J Neurochem. 114(3):672-686. PMID: 20477942(https://pubmed.ncbi.nlm.nih.gov/20477942/)
Cardozo-Pelaez F, et al. (2000). Oxidative DNA damage in the aging brain. J Neurosci. 20(24):9112-9121. PMID: 11124986(https://pubmed.ncbi.nlm.nih.gov/11124986/)
Englander EW, et al. (2005). Brain capacity for repair of oxidatively damaged DNA. Adv Exp Med Biol. 570:251-262. PMID: 15702566(https://pubmed.ncbi.nlm.nih.gov/15702566/)
Weissman L, et al. (2007). Defective DNA repair in mitochondrial DNA. Mitochondrion. 7(5):312-320. PMID: 17627813(https://pubmed.ncbi.nlm.nih.gov/17627813/)
See Also
[OGG1 Gene](/proteins/ogg1-protein)
[PARP1 Gene](/proteins/parp1-protein)
[DNA Damage Response in Neurodegeneration](/mechanisms/dna-damage-response)
[Human Protein Atlas: MUTYH](https://www.proteinatlas.org/gene/MUTYH)
Background
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.
Allen Brain Atlas Resources
The Allen Brain Atlas provides comprehensive gene expression data across brain regions and cell types.
[Allen Human Brain Atlas](https://human.brain-map.org/) — Gene expression data across the adult human brain
[Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — Gene expression in mouse brain
[Allen Cell Type Atlas](https://celltypes.brain-map.org/) — Single-cell transcriptomics data
[Allen Brain Map Portal](https://portal.brain-map.org/) — Access to all Allen Institute brain data
Search for expression data on the Allen Brain Atlas:
[Human Brain Atlas search for MUTYH](https://human.brain-map.org/microarray/search/show?search_term=MUTYH)
[Mouse Brain Atlas search for MUTYH](https://mouse.brain-map.org/search/index.html?query=MUTYH)
References
Shibutani S, et al, Insertion of bases at apurinic/apyrimidinic sites during DNA synthesis (1991)
Nakabeppu Y, et al, The repair of 8-oxoguanine in mitochondrial DNA and neurodegeneration (2014)
Goto M, et al, MUTYH variants and Parkinson's disease risk (2016)
Markkanen E, et al, Not all DNA repair is created equal: 8-oxoguanine metabolism (2015)
van Loon B, et al, The base excision repair pathway in brain (2010)
Cardozo-Pelaez F, et al, Oxidative DNA damage in the aging brain (2000)
Englander EW, et al, Brain capacity for repair of oxidatively damaged DNA (2005)
Weissman L, et al, Defective DNA repair in mitochondrial DNA (2007)
Pathway Diagram
The following diagram shows the key molecular relationships involving MUTYH Gene discovered through SciDEX knowledge graph analysis: