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UniProtKB/Swiss-Prot P43246: Variant p.His639Arg

DNA mismatch repair protein Msh2
Gene: MSH2
Variant information

Variant position:  639
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Histidine (H) to Arginine (R) at position 639 (H639R, p.His639Arg).
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 (H) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Variant description:  In HNPCC1; 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:  639
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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                         YVRPAIL-----EKGQG------------------------------RIILKASRHACVEVQDEIAFIPNDVYFEK

Mouse                         YVRPVIL-----EKGKG------------------------

Rat                           YVRPVIL-----EKGKG------------------------

Bovine                        YVRPVIL-----EKGRG------------------------

Drosophila                    YVRPKML-----EEGAR------------------------

Slime mold                    FIRPEIIPLGSDENGAG------------------------

Baker's yeast                 YIRPKLHP----MDSER------------------------


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.

Chain 2 – 934 DNA mismatch repair protein Msh2
Region 601 – 671 Interaction with EXO1

Literature citations

Identification of concurrent germ-line mutations in hMSH2 and/or hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds.
Nakahara M.; Yokozaki H.; Yasui W.; Dohi K.; Tahara E.;
Cancer Epidemiol. Biomarkers Prev. 6:1057-1064(1997)
Cited for: VARIANTS HNPCC1 THR-110; ARG-639; LYS-647; HIS-656; THR-679; VAL-729 AND ILE-732;

Functional analysis of HNPCC-related missense mutations in MSH2.
Lutzen A.; de Wind N.; Georgijevic D.; Nielsen F.C.; Rasmussen L.J.;
Mutat. Res. 645:44-55(2008)
Cited for: CHARACTERIZATION OF VARIANTS HNPCC1 HIS-167; THR-305: LEU-622; ARG-639; ARG-674; PHE-697 AND THR-834;

A rapid and cell-free assay to test the activity of lynch syndrome-associated MSH2 and MSH6 missense variants.
Drost M.; Zonneveld J.B.; van Hees S.; Rasmussen L.J.; Hofstra R.M.; de Wind N.;
Hum. Mutat. 33:488-494(2012)
Cited for: CHARACTERIZATION OF VARIANTS HNPCC1 MET-44; VAL-45; HIS-167; THR-305; PHE-390; ASN-596 DEL; ARG-639; ARG-674; PHE-697; PHE-723 AND GLY-886; CHARACTERIZATION OF VARIANTS ASP-165; HIS-177; VAL-272; LEU-385; LEU-519; ALA-675; GLU-759; VAL-805; GLY-843 AND LEU-860;

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.