MSH2 variant:MSH3-defective DNA mismatch repair

Stable Identifier
Reaction [transition]
Homo sapiens
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MSH2 is homologous to the E. coli MutS gene and is involved in DNA mismatch repair (MMR) (Fishel et al., 1994).
Evidence to support a role for the mismatch repair genes human mutS homolog 2 (hMSH2) in the etiology of colorectal cancer has come from linkage analysis, segregation studies, and molecular biologic analysis. More recently, carriers of potentially pathogenic mutations in the hMSH2 genes have consistently been shown to be at a greatly increased risk of developing colorectal cancer compared with the general population.
Two variants are described here MSH2 ARG406TER and MSH2 GLN601TER (Leach et al., 1993, Kolodner et al., 1994). Both variants disrupt the formation of the MSH2:MSH3 complex. The MSH2 ARG406TER occurred in a kindred with hereditary nonpolyposis colorectal cancer. The variant contains a CGA-to-TGA transition in codon 406, resulting in change of arginine to a stop.
The MSH2 GLN601TER variant occurs in a kindred with characteristics of the Muir-Torre syndrome (Kolodner et al., 1994).
Literature References
PubMed ID Title Journal Year
7713503 Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations

Kolodner, RD, Burn, J, Rao, MR, Chapman, P, Lipford, J, Morrison, P, Hall, NR, Wirth, L, Kane, MF, Finan, PJ

Genomics 1994
8261515 Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

Aaltonen, LA, Leach, FS, Papadopoulos, N, Nyström-Lahti, M, Nicolaides, NC, Jen, J, Parsons, R, Sistonen, P, Peltomäki, P, Liu, B

Cell 1993
Normal reaction
Functional status

Loss of function of MSH2 Variants [nucleoplasm]

Name Identifier Synonyms
colorectal cancer DOID:9256
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