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@genomenon.com

Gene CDK12
Variant G909R
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions CDK12 G909R lies within the protein kinase domain of the Cdk12 protein (UniProt.org). G909R confers a loss of function to the Cdk12 protein as demonstrated by its inability to restore Cdk12 function in Cdk12 depleted cells and by loss of activity in reporter assays (PMID: 24554720, PMID: 25712099).
Associated Drug Resistance
Category Variants Paths

CDK12 mutant CDK12 inact mut CDK12 G909R

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_016507.4
gDNA chr17:g.39511587G>A
cDNA c.2725G>A
Protein p.G909R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_047436265.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436276.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524894.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436255.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
NM_016507 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
NM_015083.4 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436279.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436259.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524903 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_024450801.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436258.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524892 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
NM_015083.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436270.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524907.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024750 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436267.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524907.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436277.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
NM_015083 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436260.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524899.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524907 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524900.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024751 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524905 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436293.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524903.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024749 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524893.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524894.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024744 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436278.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524895.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436266.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024748.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
NM_016507.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436289.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524902 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024751.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436257.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524892.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524897.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524895.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524896 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524906.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524895 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024752.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436256.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524902.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_005257458.4 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436288.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524898.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436272.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024747.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
NM_016507.4 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524905.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524897 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024745 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024746 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024749.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524900 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436273.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024752 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524896.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524898.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524901.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524899 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524893.3 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524906.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436261.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436274.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524894 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436287.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436268.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524893 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524897.2 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524901 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524898 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_005257458 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024750.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024748 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436275.1 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_017024747 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_011524906 chr17:g.39511587G>A c.2725G>A p.G909R RefSeq GRCh38/hg38
XM_047436269.1 chr17:g.39511587G>A c.2725G>A p.G909R 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
CDK12 inact mut prostate cancer sensitive Olaparib Phase II Actionable In a Phase II trial (TOPARP-B), Lynparza (olaparib) treatment resulted in a composite overall response rate of 25.0% (5/20) and a RECIST objective response rate of 0% (0/18) in patients with castration-resistant prostate cancer harboring deleterious CDK12 mutations (PMID: 31806540; NCT01682772). 31806540
CDK12 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 CDK12 (NCCN.org). detail...
CDK12 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 0.74 in CDK12-mutant patients (PMID: 32343890; NCT02987543). detail... 32343890 detail...
CDK12 inact mut prostate cancer predicted - sensitive unspecified PARP inhibitor Clinical Study - Meta-analysis Actionable In a combined analysis of 6 clinical trials, PARP inhibitor therapy improved radiographic progression-free survival (17 vs 14 mo, HR 0.5) and overall survival (36 vs 27 mo, HR 0.63) compared to placebo when combined with AR pathway inhibitors in patients with metastatic castration-resistant prostate cancer harboring CDK12 mutations, and resulted in an objective response rate of 5% (2/44) as monotherapy (PMID: 38484203; NCT02987543, NCT03732820, NCT03395197, NCT03748641, NCT02952534, NCT03148795). 38484203
CDK12 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 CDK12, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). detail... 37285865
CDK12 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 CDK12 mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). detail...
CDK12 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 CDK12 mutation presumed to be inactivating, with no confirmed radiographic responses in 10 evaluable patients and a PSA response in 1 patient with biallelic CDK12 alterations in the overall population of 15 patients, and a clinical benefit rate of 20% (3/15) at 6 months and 7.1% (1/14) at 12 months (PMID: 32086346; NCT02952534). 32086346
CDK12 inact mut Advanced Solid Tumor predicted - sensitive RP-3500 Case Reports/Case Series Actionable In a Phase I/II trial (TRESR), RP-3500 treatment resulted in a response rate of 12% (13/113), clinical benefit rate (CBR) of 42% (47/113), and median progression-free survival (mPFS) of 15 weeks in solid tumor patients with inactivating mutations in DNA damage repair genes, including CDK12 with a CBR of 28.6% (2/7), and with a CBR of 75% and mPFS of 35 weeks in 20 ovarian cancer patients (PMID: 37277454; NCT04497116). 37277454
CDK12 mutant prostate cancer predicted - sensitive unspecified PD-1 antibody Case Reports/Case Series Actionable In a clinical study, 50% (2/4) of prostate cancer patients with mutant CDK12 responded to an unspecified checkpoint inhibitor immunotherapy and had a corresponding decrease in prostate specific antigen (PMID: 29906450). 29906450