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MSH2 (human mutS homolog 2)

Written2005-07Enric Domingo, Sim Schwartz Jr
Oncologia Molecular i Envelliment, Centre d'Investigacions en Bioqumica i Biologia Molecular (CIBBIM) Hospital Universitari Vall d'Hebron Passeig Vall d'Hebron 119-129 Barcelona 08035, Catalonia, Spain

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Other aliasCOCA1
LocusID (NCBI) 4436
Atlas_Id 340
Location 2p21  [Link to chromosome band 2p21]
Location_base_pair Starts at and ends at bp from pter
Local_order Between the FLJ40172 and MSH6 genes.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CCDC149 (4p15.2) / MSH2 (2p21)DNAI1 (9p13.3) / MSH2 (2p21)EPCAM (2p21) / MSH2 (2p21)
MSH2 (2p21) / MSH2 (2p21)MSH2 (2p21) / RIPOR2 (6p22.3)MSH2 (2p21) / SLC3A1 (2p21)
MSH2 (2p21) / TTC7A (2p21)PARP12 (7q34) / MSH2 (2p21)REEP3 (10q21.3) / MSH2 (2p21)


  Diagram of the MSH2 gene. Exons are represented by boxes (in scale) transcribed and untranscribed sequences in blue and yellow, with exon numbers on top and number of base pairs at the bottom. Introns are represented by black bars (not in scale) and the number of base pairs indicated. The arrows show the ATG and the stop codons respectively.
Description The MSH2 gene is composed of 16 exons spanning in a region of 80098 bp.
Transcription The transcribed mRNA has 3145 bp.


  Diagram of the MSH2 protein in scale. Numbers inside the blue boxes indicate the exon from which is translated each part of the protein. The boxes inside represent the DNA binding domain (red), the hMSH3/hMSH6 interaction domain (yellow) and the MutL homologs interaction domain (green); C: Carboxyl-terminal; N: Amino-terminal.
Description Aminoacids: 934. Molecular Weight: 104.7 kDa. MSH2 is a protein involved in the mismatch repair process after DNA replication. It contains a DNA binding domain and two interaction domains, one for MSH3 or MSH6 and the other for MutL homologs (MLH1 and PMS2), located in two different regions of the gene.
Localisation Nuclear
Function MSH2 can bind to MSH6 or to MSH3 to form the MutS alpha or the MutS beta complexes respectively. While MutS alpha complex binds to base-base and insertion-deletion mismatches, MutS beta only binds to insertion-deletion mismatches. Upon binding to the mismatch, the MutS complex associates with the MutL complex (composed of MLH1 and PMS2), and recruits the proteins needed for DNA excision and repair. (See also: Repair of DNA double-strand breaks
Homology MSH2 is homologue to the bacterial MutS gene and MSH2 homologues are also present in eukaryotes.


Germinal There are over 300 MSH2 germline mutations described along the gene that cause hereditary non-polyposis colorectal cancer (HNPCC, see below). Mutations do not occur in any particular hotspot or region of the gene and include either nucleotide substitutions (missense, nonsense and splicing errors) and insertions/deletions (gross or small). In most of these mutations the resulting protein is truncated. Although rare there are described some founding mutations which account for a high proportion of the HNPCC tumours in some specific populations. Some germline genetic changes have also been described in exons and introns as non pathogenic.
Somatic Some sporadic mismatch repair deficient cases (sporadic MSI) with somatic MSH2 mutations are described.

Implicated in

Entity HNPCC (Hereditary Non Polyposis Colorectal Cancer)
Disease Predisposition to develop cancer, preferentially colorectal, but also in endometrium, , urinary tract, stomach, small bowel, biliary tract and brain.
Oncogenesis MSH2 mutations in HNPCC account for about 25% of the total cases approximately. These mutations are inherited in one allele and later the other allele is lost by LOH. This leads to mismatch repair deficiency in this patients, which is the cause of the accumulation of mutations along the genome, causing microsatellite instability (MSI) and promoting tumorigenesis. It has also been described that low levels of MSI characterize MLH1 and MSH2 HNPCC carriers before tumour diagnosis.
Entity MSI (MicroSatellite Instability)
Note Tumours in which the molecular feature that leads to cancer is the lost of the mismatch repair (MMR) system.
Disease This phenotype is present in 15% of colorectal, gastric and endometrial cancer, and has a lower incidence in some other tissues.
Prognosis MSI tumours have better prognosis than the MicroSatellite Stable (MSS).
Oncogenesis Few sporadic cases and about 25% of the HNPCC are due to different mutations in MSH2. These mutations are germline in HNPCC.
Entity Muir-Torre syndrome
Disease Coincidence of at least one sebaceous adenoma, epithelioma or carcinoma and one internal malignancy.
Oncogenesis Muir-Torre syndrome is mainly due to inherited MSH2 mutations.


Low levels of microsatellite instability characterize MLH1 and MSH2 HNPCC carriers before tumor diagnosis.
Alazzouzi H, Domingo E, Gonz´lez S, Blanco I, Armengol M, Espín E, Plaja A, Schwartz S, Capella G, Schwartz S Jr
Human molecular genetics. 2005 ; 14 (2) : 235-239.
PMID 15563510
Microsatellite instability in inherited and sporadic neoplasms.
Eshleman JR, Markowitz SD
Current opinion in oncology. 1995 ; 7 (1) : 83-89.
PMID 7696368
The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R
Cell. 1993 ; 75 (5) : 1027-1038.
PMID 8252616
DNA mismatch repair defects: role in colorectal carcinogenesis.
Jacob S, Praz F
Biochimie. 2002 ; 84 (1) : 27-47.
PMID 11900875
A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States.
Lynch HT, Coronel SM, Okimoto R, Hampel H, Sweet K, Lynch JF, Barrows A, Wijnen J, van der Klift H, Franken P, Wagner A, Fodde R, de la Chapelle A
JAMA : the journal of the American Medical Association. 2004 ; 291 (6) : 718-724.
PMID 14871915
A genotype-phenotype correlation in HNPCC: strong predominance of msh2 mutations in 41 patients with Muir-Torre syndrome.
Mangold E, Pagenstecher C, Leister M, Mathiak M, Rütten A, Friedl W, Propping P, Ruzicka T, Kruse R
Journal of medical genetics. 2004 ; 41 (7) : 567-572.
PMID 15235030
DNA mismatch repair and mutation avoidance pathways.
Marti TM, Kunz C, Fleck O
Journal of cellular physiology. 2002 ; 191 (1) : 28-41.
PMID 11920679
Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review.
Mitchell RJ, Farrington SM, Dunlop MG, Campbell H
American journal of epidemiology. 2002 ; 156 (10) : 885-902.
PMID 12419761


This paper should be referenced as such :
Domingo, E ; Schwartz, S Jr
MSH2 (human mutS homolog 2)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):291-292.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]
  Breast tumors : an overview
Colon: Colorectal adenocarcinoma
Breast: Ductal carcinoma
Gastric Tumors: an overview
Liver tumors: an overview
Head and Neck: Oral leukoplakia
Uterus Tumours: an Overview

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
  Hereditary pancreatic cancer Lynch Syndrome

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)4436
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
Other databaseUMD-MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)). Curator: S. Olschwang
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 18 17:44:08 CEST 2018

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