Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene CHEK2
Variant P85R
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions CHEK2 P85R does not lie within any known functional domains of the Chek2 protein (UniProt.org). P85R results in decreased kinase activity in an in vitro assay (PMID: 22114986), and therefore, is predicted to lead to a loss of Chek2 protein function.
Associated Drug Resistance
Category Variants Paths

CHEK2 mutant CHEK2 inact mut CHEK2 P85R

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Transcript NM_007194.4
gDNA chr22:g.28734468G>C
cDNA c.254C>G
Protein p.P85R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001349956.1 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529842.2 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529844 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_024452148.1 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529844.3 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529839.3 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_006724116.3 chr22:g.28710055G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529842 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_006724116 chr22:g.28710055G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_017028560.2 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_001349956.2 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_024452149.2 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529840.4 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_047441104.1 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529841.1 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_047441105.1 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_047441106.1 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_145862.2 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529840.3 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529840 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_007194.4 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529844.2 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_017028560 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_007194.3 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_145862 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529839.2 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_007194 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_024452149.1 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_001005735.1 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_145862.2 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_001005735 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_017028560.1 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529841 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_006724116.2 chr22:g.28710055G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_024452148.2 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_047441107.1 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529839 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529843 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38
XM_011529842.3 chr22:g.28734498G>C c.254C>G p.P85R RefSeq GRCh38/hg38
NM_001005735.2 chr22:g.28734468G>C c.254C>G p.P85R RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CHEK2 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, HR for progression or death was 0.87 in CHEK2-mutant patients (PMID: 32343890; NCT02987543). detail... detail... 32343890
CHEK2 inact mut prostate cancer sensitive Olaparib Guideline Actionable Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in CHEK2 (NCCN.org). detail...
CHEK2 inact mut prostate cancer no benefit Rucaparib Phase II Actionable In a Phase II trial (TRITON2), activity of Rubraca (rucaparib) was limited in the cohort of patients with metastatic castrate-resistant prostate cancer harboring a CHEK2 mutation presumed to be inactivating, with a radiographic partial response in 1 patient who had a co-occurring ATM alteration out of 9 evaluable patients, and PSA response rate of 16.7% (2/12), and a clinical benefit rate of 37.5% (3/8) at 6 months, with no patients remaining on treatment at 12 months (PMID: 32086346; NCT02952534). 32086346
CHEK2 inact mut prostate cancer predicted - sensitive Abiraterone + Niraparib + Prednisone Phase III Actionable In a Phase III trial (MAGNITUDE), Zejula (niraparib) in combination with Zytiga (abiraterone) and Adasone (prednisone) (AAP) improved radiographic progression-free survival (HR 0.64) compared to placebo and AAP in patients with metastatic castration-resistant prostate cancer harboring inactivating mutations in the homologous recombination repair (HRR)-associated genes (CHEK2 or HDAC2), with a HR of 0.66 in patients with CHEK2 mutations (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 5020; NCT03748641). detail...
CHEK2 inact mut prostate cancer sensitive Enzalutamide + Talazoparib FDA approved Actionable In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including CHEK2, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). detail... 37285865
CHEK2 inact mut prostate cancer sensitive Enzalutamide + Talazoparib Guideline Actionable Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic CHEK2 mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). detail...
CHEK2 mutant breast cancer no benefit Olaparib Case Reports/Case Series Actionable In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in 7 patients with metastatic breast cancer harboring only germline mutations in CHEK2 (PMID: 33119476; NCT03344965). 33119476
CHEK2 mutant Advanced Solid Tumor no benefit Olaparib Phase II Actionable In a Phase II trial, Lynparza (olaparib) treatment did not demonstrate clinical activity in patients with advanced solid tumors harboring ATM (n=13) or CHEK2 (n=14) mutations (Ann Oncol (2023) 34 (suppl_2): S242; NCT03967938). detail...
CHEK2 mutant prostate cancer not applicable N/A Guideline Risk Factor Germline CHEK2 mutations are associated with increased risk of developing prostate cancer (NCCN.org). detail...