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UniProtKB/Swiss-Prot O96017: Variant p.Ile157Thr

Serine/threonine-protein kinase Chk2
Gene: CHEK2
Variant information

Variant position:  157
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Isoleucine (I) to Threonine (T) at position 157 (I157T, p.Ile157Thr).
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 hydrophobic (I) to medium size and polar (T)
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

Variant description:  Might influence susceptibility to different types of cancer; 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.



Sequence information

Variant position:  157
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:   RTYSKKHFRIFREVGPKNSY  I AYIEDHSGNGTFVNTELVGK
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                         RTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGK

Mouse                         RTYSKKHFRIFREMGPKNCYIVYIEDHSGNGTFVNTELIGK

Caenorhabditis elegans        RFISKIQFSIDRDTETRR---IYLHDHSRNGTLVNQEMIGK

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 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 148 – 543 Missing. In isoform 10.
Alternative sequence 150 – 165 VGPKNSYIAYIEDHSG -> ENLSCPYRIWFNFCLF. In isoform 6.
Beta strand 154 – 162


Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LEU-85; THR-157; MET-436; LYS-446; ILE-447; SER-448; LYS-501 AND VAL-512;

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;

Mutation analysis of the CHK2 gene in families with hereditary breast cancer.
Allinen M.; Huusko P.; Maentyniemi S.; Launonen V.; Winqvist R.;
Br. J. Cancer 85:209-212(2001)
Cited for: VARIANT THR-157;

Mutations in CHEK2 associated with prostate cancer risk.
Dong X.; Wang L.; Taniguchi K.; Wang X.; Cunningham J.M.; McDonnell S.K.; Qian C.; Marks A.F.; Slager S.L.; Peterson B.J.; Smith D.I.; Cheville J.C.; Blute M.L.; Jacobsen S.J.; Schaid D.J.; Tindall D.J.; Thibodeau S.N.; Liu W.;
Am. J. Hum. Genet. 72:270-280(2003)
Cited for: VARIANTS PROSTATE CANCER LYS-64; PRO-145; ARG-167; CYS-180; HIS-180; CYS-181; HIS-181; LYS-239; PHE-251; HIS-318; PRO-323; CYS-327 AND LYS-476; VARIANT THR-157;

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: VARIANTS GLY-117; TRP-145 AND THR-157;

CHEK2 variants associate with hereditary prostate cancer.
Seppaelae E.H.; Ikonen T.; Mononen N.; Autio V.; Roekman A.; Matikainen M.P.; Tammela T.L.J.; Schleutker J.;
Br. J. Cancer 89:1966-1970(2003)
Cited for: VARIANT THR-157;

CHEK2 is a multiorgan cancer susceptibility gene.
Cybulski C.; Gorski B.; Huzarski T.; Masojc B.; Mierzejewski M.; Debniak T.; Teodorczyk U.; Byrski T.; Gronwald J.; Matyjasik J.; Zlowocka E.; Lenner M.; Grabowska E.; Nej K.; Castaneda J.; Medrek K.; Szymanska A.; Szymanska J.; Kurzawski G.; Suchy J.; Oszurek O.; Witek A.; Narod S.A.; Lubinski J.;
Am. J. Hum. Genet. 75:1131-1135(2004)
Cited for: VARIANT 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;

A novel founder CHEK2 mutation is associated with increased prostate cancer risk.
Cybulski C.; Huzarski T.; Gorski B.; Masojc B.; Mierzejewski M.; Debniak T.; Gliniewicz B.; Matyjasik J.; Zlowocka E.; Kurzawski G.; Sikorski A.; Posmyk M.; Szwiec M.; Czajka R.; Narod S.A.; Lubinski J.;
Cancer Res. 64:2677-2679(2004)
Cited for: VARIANT THR-157;

Limited relevance of the CHEK2 gene in hereditary breast cancer.
Dufault M.R.; Betz B.; Wappenschmidt B.; Hofmann W.; Bandick K.; Golla A.; Pietschmann A.; Nestle-Kraemling C.; Rhiem K.; Huettner C.; von Lindern C.; Dall P.; Kiechle M.; Untch M.; Jonat W.; Meindl A.; Scherneck S.; Niederacher D.; Schmutzler R.K.; Arnold N.;
Int. J. Cancer 110:320-325(2004)
Cited for: VARIANT THR-157;

CHEK2 variant I157T may be associated with increased breast cancer risk.
Kilpivaara O.; Vahteristo P.; Falck J.; Syrjaekoski K.; Eerola H.; Easton D.; Bartkova J.; Lukas J.; Heikkilae P.; Aittomaeki K.; Holli K.; Blomqvist C.; Kallioniemi O.-P.; Bartek J.; Nevanlinna H.;
Int. J. Cancer 111:543-547(2004)
Cited for: VARIANT THR-157;

Association of two mutations in the CHEK2 gene with breast cancer.
Bogdanova N.; Enbetaen-Dubrowinskaja N.; Feshchenko S.; Lazjuk G.I.; Rogov Y.I.; Dammann O.; Bremer M.; Karstens J.H.; Sohn C.; Doerk T.;
Int. J. Cancer 116:263-266(2005)
Cited for: VARIANT 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: VARIANTS GLY-117; GLN-137; TRP-145; THR-157 AND HIS-180;

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.