PDB rendering based on 1x51.
|RNA expression pattern|
MUTYH (mutY Homolog (E. coli)) is a human gene encoding a DNA glycosylase, MUTYH glycosylase, involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. Mutations in this gene result in heritable predisposition to colon and stomach cancer. Multiple transcript variants encoding different isoforms have been found for this gene.
The MUTYH gene is located on the short (p) arm of chromosome 1 between positions 34.3 and 32.1, from base pair 45,464,007 to base pair 45,475,152.
Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MUTYH-associated polyposis). Polyps caused by mutated MUTYH do not appear until adulthood and are less numerous than those found in patients with APC gene mutations. The risk for developing colon cancer, when colon screening has not commenced, is about 43 to 100% (MUTYH-Associated Polyposis, genereviews 2012)
Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. Both copies of the MYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme<Nielsen 2011>. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian Europeans are exchanges of amino acids (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine with cysteine at position 179 (also written as p.Tyr179Cys (p.Y179C) or, when describing the nucleotide change, written as c.536A>G) The other common mutation switches the amino acid glycine with aspartic acid at position 396 (also written as p.Gly396Asp(G396D)or c.1187G>A)
- "Entrez Gene: MUTYH mutY homolog (E. coli)".
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- Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC et al. (Jul 2004). "MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps". Gastroenterology 127 (1): 9–16. doi:10.1053/j.gastro.2004.03.070. PMID 15236166.
- Brand R, Nielsen M, Lynch H, Infante E (2012). "MUTYH-Associated Polyposis.". GeneReviews®. PMID 23035301.
- Nielsen M, Morreau H, Vasen HF, Hes FJ (Jul 2011). "MUTYH-associated polyposis (MAP)". Critical Reviews in Oncology/Hematology 79 (1): 1–16. doi:10.1016/j.critrevonc.2010.05.011. PMID 20663686.