Defective MUTYH substrate processing

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

MUTYH disease variants underlying the MUTYH-associated polyposis (MAP), also known as familial adenomatous polyposis 2 (FAP2), show impaired catalytic activity with respect to cleaving adenine mispaired with 8-oxoguanine (OGUA:Ade, also known as 8-oxoG:A). For some of the mutants, defective substrate processing is further aggravated by reduced substrate binding. MUTYH alpha-3 isoform (MUTYH-3) mutants and MUTYH gamma-3 isoform (MUTYH-6) mutants with experimentally demonstrated deficiency in catalytic activity include missense mutants MUTYH-3 Y165C (MUTYH-6 Y151C), MUTYH-3 R171W, MUTYH-3 R227W, MUTYH-3 R231H, MUTYH-3 R231L, MUTYH-3 V232F, MUTYH-3 R260Q, MUTYH-3 G272E, MUTYH-3 P281L, MUTYH-3 P391L (MUTYH-6 P377L), MUTYH-3 Q324H, MUTYH-3 Q324R,, MUTYH-3 A359V, MUTYH-3 G382D (MUTYH-6 G368D), MUTYH-3 A459D, MUTYH-6 R154H, MUTYH-6 I195V, MUTYH-6 M255V and MUTYH-3 L360P, in-frame indel mutants MUTYH-3 W138_M139insIW (also known as MUTYH 137insIW) and MUTYH-3 E466del (MUTYH-6 E452del), nonsense mutants MUTYH-3 Y90*, MUTYH-3 Q377*, and MUTYH-3 E466*, and frameshift mutant MUTYH-3 A368fs26* (commonly known as MUTYH 1103delC) (Jones et al. 2002, Chmiel et al. 2003, Wooden et al. 2004, Parker et al. 2005, Bai et al. 2005, Alhopuro et al. 2005, Bai et al. 2007, Ali et al. 2008, Yanaru-Fujisawa et al. 2008, Kundu et al. 2009, Forsbring et al. 2009, Molatore et al. 2010, D'Agostino et al. 2010, Goto et al. 2010, Raetz et al. 2012, Shinmura et al. 2012).

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
16134146 A novel functionally deficient MYH variant in individuals with colorectal adenomatous polyposis

Aaltonen, LA, Karhu, A, Enholm, S, Alhopuro, P, Järvinen, HJ, Parker, AR, Eshleman, JR, Mecklin, JP, Lehtonen, R

Hum. Mutat. 2005
19443904 Catalytically impaired hMYH and NEIL1 mutant proteins identified in patients with primary sclerosing cholangitis and cholangiocarcinoma

Forsbring, M, Boberg, KM, Bergquist, A, Schrumpf, E, Karlsen, TH, Dalhus, B, Vik, ES, Bjørås, M, Alseth, I

Carcinogenesis 2009
15673720 Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis

Sampson, JR, Wilson, TM, Bai, H, Cheadle, JP, Jones, S, Guan, X, Lu, AL

Nucleic Acids Res. 2005
18422726 Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis

Ushijima, Y, Iida, M, Esaki, M, Matsumoto, T, Hirahashi, M, Yanaru-Fujisawa, R, Yao, T, Nakabeppu, Y, Gushima, M

Clin. Genet. 2008
12393807 Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations

Sampson, JR, Emmerson, P, Jordan, S, Cheadle, JP, Maynard, J, Best, JM, Jones, S, Williams, GT

Hum. Mol. Genet. 2002
20848659 Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer

Shinmura, K, Goto, M, Sugimura, H, Tsuneyoshi, T, Nakabeppu, Y, Yamada, H, Tao, H

Hum. Mutat. 2010
23322991 Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis

Matsuura, S, Shinmura, K, Matsuda, T, Goto, M, Sugimura, H, Tao, H

World J. Gastroenterol. 2012
22926731 Cancer-associated variants and a common polymorphism of MUTYH exhibit reduced repair of oxidative DNA damage using a GFP-based assay in mammalian cells

Brinkmeyer, MK, Chang, C, Kundu, S, Xie, Y, David, SS, Raetz, AG

Carcinogenesis 2012
17081686 Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis

Wilson, TM, Grist, S, Bai, H, Suthers, G, Gardner, J, Lu, AL

Cancer Lett. 2007
19836313 Adenine removal activity and bacterial complementation with the human MutY homologue (MUTYH) and Y165C, G382D, P391L and Q324R variants associated with colorectal cancer

Brinkmeyer, MK, Kundu, S, David, SS, Livingston, AL

DNA Repair (Amst.) 2009
15036665 Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer

Bassett, HM, Wood, TG, McCullough, AK, Wooden, SH

Cancer Lett. 2004
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
Cite Us!