UniProtKB/Swiss-Prot Q9UQ84: Variant p.Thr439Met

Exonuclease 1
Gene: EXO1
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Variant information Variant position:

439 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Threonine (T) to Methionine (M) at position 439 (T439M, p.Thr439Met). 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 (T) to medium size and hydrophobic (M) 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
Polymorphism:

Most naturally occurring variants in this protein are not associated with familial disposition to hereditary non-polyposis colorectal cancer (HNPCC) (PubMed:12517792). Furthermore, germline deletions involving this locus are not associated with clinically manifested colorectal tumors (PubMed:14623461). Additional information on the polymorphism described.
Variant description:

May be associated with an increased risk of colorectal cancer. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs4149963 [ dbSNP | Ensembl ]

Sequence information Variant position:

439 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

846 The length of the canonical sequence.
Location on the sequence:

RPRSAELSEDDLLSQYSLSF T KKTKKNSSEGNKSLSFSEVF 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                         RPRSA-ELSEDDLLSQYSLSFTKKTKKNSSEGNK-------SLSFSEVF

Mouse                         RPRNE-ALAEDDLLSQYS-SVSKKIKENGCGDGT-------

Xenopus laevis                RSYED-GVSDTDLISQYSFSKNKKARPDGDDPMQQ------

Zebrafish                     RPREDTSLSVDDLLEQYTAGVKRHCPET-------------

Drosophila                    RLEQA-KQTEAELFNMYSFKAKRRRSPSREDSVDQERTPPP

Slime mold                    DCLND-DDDDESIILSNNLNNQENVLESDCEFDDDDDQRGI

Baker's yeast                 QAEDKLTMAIKRRKLSNANVVQETLKDTRSKFFNK-PSMTV

Fission yeast                 RTHLA-NDISSEKQSIKSANEKAYVTPKSNSL---------

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.

Type	Positions	Description
Chain	1 – 846	Exonuclease 1
Region	388 – 490	Interaction with MLH1
Modified residue	422 – 422	Phosphoserine
Modified residue	454 – 454	Phosphoserine
Mutagenesis	419 – 419	R -> A. Complete loss of nuclear localization.
Mutagenesis	454 – 454	S -> A. No rescue of HU-induced degradation. No rescue of HU-induced degradation; when associated with A-714. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-621 and A-714.

Literature citations
Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ILE-76; GLY-93; SER-279; SER-299; ARG-354; ASN-428; MET-439; TYR-456; MET-458; LEU-460; THR-503; LYS-589; GLN-634; GLY-670; CYS-723; LEU-757 AND GLU-759; Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.
Thompson E.; Meldrum C.J.; Crooks R.; McPhillips M.; Thomas L.; Spigelman A.D.; Scott R.J.;
Clin. Genet. 65:215-225(2004)
Cited for: VARIANTS MET-439; GLY-670; PRO-726 AND LEU-757; Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population.
Yamamoto H.; Hanafusa H.; Ouchida M.; Yano M.; Suzuki H.; Murakami M.; Aoe M.; Shimizu N.; Nakachi K.; Shimizu K.;
Carcinogenesis 26:411-416(2005)
Cited for: VARIANTS MET-439 AND LEU-757;

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.