MUTYH: MutY DNA Glycosylase
A key base excision repair gene associated with colorectal polyposis and cancer predisposition
Gene Information Card
| Symbol | MUTYH |
|---|---|
| Full Name | mutY DNA glycosylase |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 4595 ncbi.nlm.nih.gov/gene/4595 |
| Ensembl ID | ENSG00000132781 |
| UniProt ID | Q9UIF7 |
| OMIM ID | 604933 |
| HGNC ID | 7527 |
| Aliases | MYH, hMYH, A/G-specific adenine DNA glycosylase |
Description
The MUTYH gene encodes a DNA glycosylase involved in base excision repair (BER). It specifically excises adenine residues mispaired with 8-oxoguanine (8-oxoG), a common oxidative DNA lesion. Biallelic germline mutations in MUTYH cause MUTYH-associated polyposis (MAP), an autosomal recessive disorder characterized by multiple colorectal adenomas and increased risk of colorectal cancer. The protein also plays a role in the repair of oxidative damage in nuclear and mitochondrial DNA.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| MUTYH-associated polyposis (MAP) | Biallelic loss-of-function mutations impair repair of 8-oxoG:A mismatches, leading to G:C→T:A transversions in tumor suppressor genes (e.g., APC, KRAS). | OMIM #608456; ClinVar |
| Colorectal cancer (somatic) | Somatic MUTYH mutations or loss of heterozygosity contribute to genomic instability in sporadic colorectal tumors. | COSMIC; NCBI |
| Breast cancer | Some studies suggest MUTYH variants may increase breast cancer risk, though evidence is less consistent. | ClinVar; NCBI |
| Gastric cancer | Rare MUTYH variants have been reported in gastric cancer cases, possibly via similar oxidative damage repair defects. | COSMIC; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 5.2 | Medium |
| Small intestine | 4.8 | Medium |
| Liver | 3.1 | Low |
| Kidney | 2.9 | Low |
| Testis | 6.7 | Medium |
| Brain | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 4.3 | Cervical cancer cell line |
| HCT116 | 6.1 | Colorectal carcinoma cell line |
| HEK293 | 3.8 | Embryonic kidney cell line |
| MCF7 | 2.5 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1187G>A (p.Gly396Asp) | Missense | Common in MAP (founder mutation in European populations) | Reduced glycosylase activity; impairs 8-oxoG:A repair |
| c.536A>G (p.Tyr179Cys) | Missense | Common in MAP (founder mutation in European populations) | Severely reduced enzymatic activity; leads to G:C→T:A transversions |
| c.1437_1439delGGA (p.Glu480del) | Deletion | Rare | Loss of function; frameshift and premature truncation |
| c.933+3A>C | Splice site | Rare | Aberrant splicing; loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Most MUTYH mutations in MAP are loss-of-function, reducing or abolishing DNA glycosylase activity, leading to accumulation of oxidative DNA damage and increased mutation frequency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MUTYH.
Dominant Negative (DN)
Some missense variants (e.g., p.Gly396Asp) may exert a dominant-negative effect in heterozygous state, but MAP is recessive; dominant-negative role is not well established.
View complete mutation data：
Gene Ontology (GO)
| • base-excision repair (GO:0006284) | • damaged DNA binding (GO:0003684) |
| • hydrolase activity (GO:0016799) | • cytoplasm (GO:0005737) |
| • nucleoplasm (GO:0005654) | • mitochondrion (GO:0005739) |
Pathways
• Base excision repair (BER) – Reactome R-HSA-73894
• Oxidative stress-induced senescence – KEGG hsa04218
• Colorectal cancer – KEGG hsa05210
Protein Summary
MUTYH is a 535-amino acid DNA glycosylase that localizes to the nucleus and mitochondria. It recognizes and excises adenine mispaired with 8-oxoguanine (8-oxoG), a major oxidative lesion. The protein interacts with AP endonuclease 1 (APE1) and proliferating cell nuclear antigen (PCNA) to coordinate subsequent steps in base excision repair. Defects in MUTYH lead to G:C→T:A transversions, a hallmark of MUTYH-associated polyposis and related cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MUTYH Knockout HEK293 Cell Line | EDJ-KQ2923 | Human | 4595 | Details Get a Quote |
| MUTYH Knockout A-549 Cell Line | EDJ-KQ24020 | Human | 4595 | Details Get a Quote |
| MUTYH Knockout HCT 116 Cell Line | EDJ-KQ24021 | Human | 4595 | Details Get a Quote |
| MUTYH Knockout HeLa Cell Line | EDJ-KQ22653 | Human | 4595 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
