Gene

CDK12

cyclin dependent kinase 12

Explore in graph →CI-GENE-00040757HGNC:24224 ENSG00000167258 NCBI 51755 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (9)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–9 of 9 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
CDK12 Inhibition1
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	2	submitted

Cohorts

Alteration frequency by cohort (148)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved148 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm

Literature

Linked publications (2)

25 per page, newest first.

pubmedPublishedShowing 1–2 of 2 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Olaparib for Metastatic Castration-Resistant Prostate Cancer.
· N Engl J Med · 2020 · PMID 32343890 · validated civic_curation pubmed
Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity.
· Cancer Res · 2014 · PMID 24240700 · validated civic_curation pubmed

CDK12 Loss-of-function4
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	E	Supports Oncogenicity	2	submitted	EID12567 Loss-of-function mutations in CDK12 disrupt transcription of DNA damage response genes (BRCA1, ATR, FANCI, FANCD2), reducing homologous recombination and sensitizing tumor cells to DNA cross-linking a… (full text at CIViC) PMID 30104286 · Lui et al., 2018 · Open in CIViC	civic
Olaparib	Ovarian Serous AdenocarcinomaALIAS	Predictive	D	Supports Sensitivity Response	4	accepted	EID623 In models of high-grade serous ovarian cancer (HGS-OVCa), CDK12 attenuation was sufficient to confer sensitivity to PARP1/2 inhibition, suppression of DNA repair via homologous recombination, and redu… (full text at CIViC) PMID 24240700 · Bajrami et al., 2014 · Open in CIViC	civic
Olaparib + Rucaparib + Talazoparib + VeliparibSubstitutes	Malignant Prostate Neoplasm	Predictive	D	Supports Sensitivity Response	2	submitted	EID12572 In prostate cancer models, CDK12 loss impaired homologous recombination deficiency and sensitized cells to PARP inhibitors (olaparib, rucaparib, talazoparib, veliparib) in a gene dosage-dependent mann… (full text at CIViC) PMID 39321214 · Chou et al., 2024 · Open in CIViC	civic
Olaparib + TalazoparibSubstitutes	Breast Carcinoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID12571 In micropapillary breast carcinoma and a subset of HER2-amplified breast cancers, genomic disruptions of CDK12 (out-of-frame rearrangements and breakpoints within the HER2 amplicon) were associated wi… (full text at CIViC) PMID 24395524 · Natrajan et al., 2014 · Open in CIViC	civic

CDK12 Loss-of-function4

(oncogenic)

Malignant NeoplasmALIAS

Oncogenic

Supports Oncogenicity

submitted

EID12567

Loss-of-function mutations in CDK12 disrupt transcription of DNA damage response genes (BRCA1, ATR, FANCI, FANCD2), reducing homologous recombination and sensitizing tumor cells to DNA cross-linking a… (full text at CIViC)

PMID 30104286 · Lui et al., 2018 · Open in CIViC

civic

Olaparib

Ovarian Serous AdenocarcinomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID623

In models of high-grade serous ovarian cancer (HGS-OVCa), CDK12 attenuation was sufficient to confer sensitivity to PARP1/2 inhibition, suppression of DNA repair via homologous recombination, and redu… (full text at CIViC)

PMID 24240700 · Bajrami et al., 2014 · Open in CIViC

civic

Olaparib + Rucaparib + Talazoparib + VeliparibSubstitutes

Malignant Prostate Neoplasm

Predictive

Supports Sensitivity Response

submitted

EID12572

In prostate cancer models, CDK12 loss impaired homologous recombination deficiency and sensitized cells to PARP inhibitors (olaparib, rucaparib, talazoparib, veliparib) in a gene dosage-dependent mann… (full text at CIViC)

PMID 39321214 · Chou et al., 2024 · Open in CIViC

civic

Olaparib + TalazoparibSubstitutes

Breast Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID12571

In micropapillary breast carcinoma and a subset of HER2-amplified breast cancers, genomic disruptions of CDK12 (out-of-frame rearrangements and breakpoints within the HER2 amplicon) were associated wi… (full text at CIViC)

PMID 24395524 · Natrajan et al., 2014 · Open in CIViC

civic

CDK12 Mutation3
Olaparib	Castration-Resistant Prostate Carcinoma	Predictive	A	Supports Sensitivity Response	4	accepted	EID11204 This randomized, open-label, phase 3 trial evaluated the PARP inhibitor olaparib in 387 men with metastatic castration-resistant prostate cancer (mCRPC) who had disease progression while receiving a n… (full text at CIViC) PMID 32343890 · de Bono et al., 2020 · Open in CIViC	civic
〃	Malignant Prostate Neoplasm	Predictive	B	Does Not Support Sensitivity Response	4	submitted	EID7473 In a phase 2 trial, patients with metastatic castration-resistant prostate cancer harboring DNA damage repair (DDR) gene aberrations were treated with olaparib. In gene testing, samples from tumor tis… (full text at CIViC) Open in CIViC	civic
Enzalutamide + TalazoparibCombination	Castration-Resistant Prostate Carcinoma	Predictive	A	Supports Sensitivity Response	1	submitted	EID11735 This phase 3 study evaluated the PARP inhibitor talazoparib in combination with the androgen receptor inhibitor enzalutamide as a first-line treatment in patients with metastatic castration-resistant… (full text at CIViC) PMID 38049622 · Fizazi et al., 2024 · Open in CIViC	civic

CDK12 Mutation3

Olaparib

Castration-Resistant Prostate Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID11204

This randomized, open-label, phase 3 trial evaluated the PARP inhibitor olaparib in 387 men with metastatic castration-resistant prostate cancer (mCRPC) who had disease progression while receiving a n… (full text at CIViC)

PMID 32343890 · de Bono et al., 2020 · Open in CIViC

civic

〃

Malignant Prostate Neoplasm

Predictive

Does Not Support Sensitivity Response

submitted

EID7473

In a phase 2 trial, patients with metastatic castration-resistant prostate cancer harboring DNA damage repair (DDR) gene aberrations were treated with olaparib. In gene testing, samples from tumor tis… (full text at CIViC)

Open in CIViC

civic

Enzalutamide + TalazoparibCombination

Castration-Resistant Prostate Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID11735

This phase 3 study evaluated the PARP inhibitor talazoparib in combination with the androgen receptor inhibitor enzalutamide as a first-line treatment in patients with metastatic castration-resistant… (full text at CIViC)

PMID 38049622 · Fizazi et al., 2024 · Open in CIViC

civic

CDK12 Amplification + ERBB2 AmplificationERBB2 CDK121
Disitamab Vedotin + Trastuzumab Deruxtecan Regimen + Trastuzumab Emtansine RegimenSubstitutes	Malignant Breast Neoplasm	Predictive	B	Supports Sensitivity Response	3	submitted	EID12569 In a real-world cohort of metastatic breast cancer (n = 63; 30 HER2-positive, 33 HER2-low), patients received HER2-targeted antibody-drug conjugates (trastuzumab deruxtecan (68.25%), disitamab vedotin… (full text at CIViC) PMID 39806366 · Huang et al., 2025 · Open in CIViC	civic

CDK12 Amplification + ERBB2 AmplificationERBB2 CDK121

Disitamab Vedotin + Trastuzumab Deruxtecan Regimen + Trastuzumab Emtansine RegimenSubstitutes

Malignant Breast Neoplasm

Predictive

Supports Sensitivity Response

submitted

EID12569

In a real-world cohort of metastatic breast cancer (n = 63; 30 HER2-positive, 33 HER2-low), patients received HER2-targeted antibody-drug conjugates (trastuzumab deruxtecan (68.25%), disitamab vedotin… (full text at CIViC)

PMID 39806366 · Huang et al., 2025 · Open in CIViC

civic