UniProtKB/SwissProt variant VAR

Variant information

Variant position:

145

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

Type of variant:

US

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 Arginine (R) to Tryptophan (W) at position 145 (R145W, p.Arg145Trp).

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 large size and basic (R) to large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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 colon cancer and LFS2; does not cause protein abrogation in familial colorectal cancer; loss of the ability to interact with and phosphorylate CDC25A and to promote CDC25A degradation in response to ionizing radiation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137853007 [ dbSNP | Ensembl ]

Sequence information

Variant position:

145

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

Protein sequence length:

543

The length of the canonical sequence.

Location on the sequence:

FDEPLLKRTDKYRTYSKKHF R IFREVGPKNSYIAYIEDHSG

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                         FDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSG

Mouse                         FDGPLLRRTDKYRTYSKKHFRIFREMGPKNCYIVYIEDHSG

Caenorhabditis elegans        FSQ-VAKDVGLYRFISKIQFSIDRDTETRR---IYLHDHSR

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 – 543	Serine/threonine-protein kinase Chk2
Domain	113 – 175	FHA
Alternative sequence	1 – 221	Missing. In isoform 13.
Alternative sequence	75 – 392	Missing. In isoform 11.
Alternative sequence	107 – 487	Missing. In isoform 3.
Alternative sequence	107 – 197	Missing. In isoform 4.
Alternative sequence	131 – 147	KRTDKYRTYSKKHFRIF -> EFRSYSFYLP. In isoform 10.
Beta strand	144 – 150

Literature citations

The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis.
Falck J.; Mailand N.; Syljuaasen R.G.; Bartek J.; Lukas J.;
Nature 410:842-847(2001)
Cited for: FUNCTION IN INTRA S-PHASE CHECKPOINT; FUNCTION IN PHOSPHORYLATION OF CDC25A; INTERACTION WITH CDC25A; MUTAGENESIS OF ASP-347; CHARACTERIZATION OF VARIANT COLON CANCER TRP-145; CHARACTERIZATION OF VARIANT THR-157;

Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.
Bell D.W.; Varley J.M.; Szydlo T.E.; Kang D.H.; Wahrer D.C.R.; Shannon K.E.; Lubratovich M.; Versalis S.J.; Isselbacher K.J.; Fraumeni J.F. Jr.; Birch J.M.; Li F.P.; Garber J.E.; Haber D.A.;
Science 286:2528-2531(1999)
Cited for: VARIANT THR-157; VARIANT COLON CANCER TRP-145;

Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.
Lee S.B.; Kim S.H.; Bell D.W.; Wahrer D.C.R.; Schiripo T.A.; Jorczak M.M.; Sgroi D.C.; Garber J.E.; Li F.P.; Nichols K.E.; Varley J.M.; Godwin A.K.; Shannon K.M.; Harlow E.; Haber D.A.;
Cancer Res. 61:8062-8067(2001)
Cited for: VARIANT LFS2 TRP-145;

Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility.
Schutte M.; Seal S.; Barfoot R.; Meijers-Heijboer H.; Wasielewski M.; Evans D.G.; Eccles D.; Meijers C.; Lohman F.; Klijn J.; van den Ouweland A.; Brady A.; Cole T.; Collins A.; Cox H.; Donaldson A.; Eeles R.; Evans G.; Gregory H.; Gray J.; Houlston R.; Lalloo F.; Lucassen A.; Mackay J.; Mitchell G.; Morrison P.; Murday V.; Narod S.; Patterson J.; Peretz T.; Phelan C.M.; Rogers M.; Schofield A.; Tonin P.; Weber B.; Weber W.; Futreal P.A.; Nathanson K.L.; Weber B.L.; Easton D.F.; Stratton M.R.; Rahman N.;
Am. J. Hum. Genet. 72:1023-1028(2003)
Cited for: VARIANT BC GLY-117; VARIANTS TRP-145 AND THR-157;

Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women.
Friedrichsen D.M.; Malone K.E.; Doody D.R.; Daling J.R.; Ostrander E.A.;
Breast Cancer Res. 6:R629-R635(2004)
Cited for: VARIANTS TRP-145 AND THR-157;

Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype.
van Puijenbroek M.; van Asperen C.J.; van Mil A.; Devilee P.; van Wezel T.; Morreau H.;
J. Pathol. 206:198-204(2005)
Cited for: VARIANT BC GLY-117; VARIANTS GLN-137; TRP-145; THR-157 AND HIS-180;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O96017: Variant p.Arg145Trp