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Structural highlights

Disease

MUTYH_HUMAN Defects in MUTYH are a cause of familial adenomatous polyposis type 2 (FAP2) [MIM:608456. A condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma.^{[1] [2] [3] [4] [5] [6]} Defects in MUTYH are a cause of gastric cancer (GASC) [MIM:613659. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.^[7]

Function

MUTYH_HUMAN Involved in oxidative DNA damage repair. Initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. Possesses both adenine and 2-OH-A DNA glycosylase activities.^[8]

References

1. ↑ Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP. Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. Nat Genet. 2002 Feb;30(2):227-32. Epub 2002 Jan 30. PMID:11818965 doi:10.1038/ng828
2. ↑ Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP. Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet. 2003 Jul 5;362(9377):39-41. PMID:12853198 doi:10.1016/S0140-6736(03)13805-6
3. ↑ Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med. 2003 Feb 27;348(9):791-9. PMID:12606733 doi:10.1056/NEJMoa025283
4. ↑ Isidro G, Laranjeira F, Pires A, Leite J, Regateiro F, Castro e Sousa F, Soares J, Castro C, Giria J, Brito MJ, Medeira A, Teixeira R, Morna H, Gaspar I, Marinho C, Jorge R, Brehm A, Ramos JS, Boavida MG. Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas. Hum Mutat. 2004 Oct;24(4):353-4. PMID:15366000 doi:10.1002/humu.9282
5. ↑ Cattaneo F, Molatore S, Mihalatos M, Apessos A, Venesio T, Bione S, Grignani P, Nasioulas G, Ranzani GN. Heterogeneous molecular mechanisms underlie attenuated familial adenomatous polyposis. Genet Med. 2007 Dec;9(12):836-41. PMID:18091433 doi:10.1097GIM.0b013e31815bf940
6. ↑ Molatore S, Russo MT, D'Agostino VG, Barone F, Matsumoto Y, Albertini AM, Minoprio A, Degan P, Mazzei F, Bignami M, Ranzani GN. MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay. Hum Mutat. 2010 Feb;31(2):159-66. doi: 10.1002/humu.21158. PMID:19953527 doi:10.1002/humu.21158
7. ↑ Kim CJ, Cho YG, Park CH, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS. Genetic alterations of the MYH gene in gastric cancer. Oncogene. 2004 Sep 2;23(40):6820-2. PMID:15273732 doi:10.1038/sj.onc.1207574
8. ↑ Ohtsubo T, Nishioka K, Imaiso Y, Iwai S, Shimokawa H, Oda H, Fujiwara T, Nakabeppu Y. Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria. Nucleic Acids Res. 2000 Mar 15;28(6):1355-64. PMID:10684930