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UniProtKB/Swiss-Prot P43246: Variant p.Gln419Lys

DNA mismatch repair protein Msh2
Gene: MSH2
Variant information

Variant position:  419
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glutamine (Q) to Lysine (K) at position 419 (Q419K, p.Gln419Lys).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (Q) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12792735, ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:9559627}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CRC; unknown pathological significance; decreased mismatch repair activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  419
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  934
The length of the canonical sequence.

Location on the sequence:   ANLQDCYRLYQGINQLPNVI  Q ALEKHEGKHQKLLLAVFVTP
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         ANLQDCYRLYQGINQLPNVIQAL------EKHEGKHQKLLLAVFVTP

Mouse                         ANLQDCYRLYQGINQLPSVIQAL------EKYEGRHQALLL

Rat                           ANLQDCYRLYQGVKQLPNVIQAL------EKYQGRHQALLL

Bovine                        ANLQDCYRLYQGINQLPNVIQAL------EKYEGKHQALFL

Drosophila                    ANLQDLFRIYQVILRTPKILKVL---------HELDNSTIE

Slime mold                    ATLEDCVNLYGIVTRLPVVLQSL------NNHSSIHQELIK

Baker's yeast                 GNLEDVLKIYQFSKRIPEIVQVFTSFLEDDSPTEPVNELVR

Fission yeast                 ASLEDVVRIYQMAKALPKIVTVL------DSLTSEHKDLVD

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 2 – 934 DNA mismatch repair protein Msh2
Cross 430 – 430 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Helix 414 – 423


Literature citations

Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer.
Konishi M.; Kikuchi-Yanoshita R.; Tanaka K.; Muraoka M.; Onda A.; Okumura Y.; Kishi N.; Iwama T.; Mori T.; Koike M.; Ushio K.; Chiba M.; Nomizu S.; Konishi F.; Utsunomiya J.; Miyaki M.;
Gastroenterology 111:307-317(1996)
Cited for: VARIANTS PHE-390 AND LYS-419;

Mutator phenotypes of common polymorphisms and missense mutations in MSH2.
Drotschmann K.; Clark A.B.; Kunkel T.A.;
Curr. Biol. 9:907-910(1999)
Cited for: CHARACTERIZATION OF VARIANTS ASP-322; PHE-390; LYS-419; TYR-506; PRO-524; LEU-622 AND PHE-697;

Oncogenic pathway of sporadic colorectal cancer with novel germline missense mutations in the hMSH2 gene.
Yamada K.; Zhong X.; Kanazawa S.; Koike J.; Tsujita K.; Hemmi H.;
Oncol. Rep. 10:859-866(2003)
Cited for: VARIANTS CRC SER-40; VAL-169; ARG-203; PHE-390; LYS-419; CYS-619 AND ARG-629; VARIANT MET-8;

Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia.
Lee S.-C.; Guo J.-Y.; Lim R.; Soo R.; Koay E.; Salto-Tellez M.; Leong A.; Goh B.-C.;
Clin. Genet. 68:137-145(2005)
Cited for: VARIANTS HNPCC1 VAL-169; PHE-390; ALA-564 AND ARG-629; VARIANT CRC LYS-419;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.