Defective MUTYH substrate binding

Stable Identifier
Homo sapiens
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For a subset of MUTYH disease variants underlying MUTYH-associated polyposis (MAP), also known as familial adenomatous polyposis 2 (FAP2), it was shown that, in addition to impaired catalytic activity, they also exhibit reduced binding to their substrate, adenine mispaired with 8-oxoguanine (OGUA:Ade, also known as 8-oxoG:A). MUTYH alpha-3 isoform (MUTYH-3) mutants with demonstrated deficient binding to OGUA:Ade include missense variants MUTYH-3 Y165C, MUTYH-3 R227W, MUTYH-3 R231L, MUTYH-3 R231H, MUTYH-3 V232F, MUTYH-3 R260Q, MUTYH-3 P281L and MUTYH-3 G382D, nonsense variants MUTYH-3 Y90*, MUTYH-3 Q377*, MUTYH-3 E466*, and frameshift variant MUTYH-3 A368fs26* (commonly known as MUTYH 1103delC) (Chmiel et al. 2003, Parker et al. 2005, Ali et al. 2008, Molatore et al. 2010, D'Agostino et al. 2010).

Literature References
PubMed ID Title Journal Year
20418187 Functional analysis of MUTYH mutated proteins associated with familial adenomatous polyposis

Albertini, AM, Bossa, C, Mazzei, F, Ranzani, GN, D'Agostino, VG, Torreri, P, Marinoni, I, Minoprio, A, Bignami, M, Petrucci, TC

DNA Repair (Amst.) 2010
15987719 Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair

Tomlinson, IP, Shi, C, Parker, AR, Eshleman, JR, Sieber, OM, Takao, M, Hua, L

Carcinogenesis 2005
18534194 Characterization of mutant MUTYH proteins associated with familial colorectal cancer

Ali, M, Bristow, R, Gallinger, S, Cleary, S, Kim, H, Cupples, C

Gastroenterology 2008
12628248 Insight into the functional consequences of inherited variants of the hMYH adenine glycosylase associated with colorectal cancer: complementation assays with hMYH variants and pre-steady-state kinetics of the corresponding mutated E.coli enzymes

Chmiel, NH, David, SS, Livingston, AL

J. Mol. Biol. 2003
19953527 MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay

Degan, P, Barone, F, Albertini, AM, Mazzei, F, Molatore, S, D'Agostino, VG, Russo, MT, Ranzani, GN, Minoprio, A, Matsumoto, Y, Bignami, M

Hum. Mutat. 2010
Name Identifier Synonyms
familial adenomatous polyposis DOID:0050424 adenomatous polyposis of the colon
colorectal cancer DOID:9256
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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