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Showing 1 to 39 of 39 entries

Molecular Profile	Treatment Approach
CDK12 A88fs	Olaparib
CDK12 D877N	Olaparib
CDK12 del	Olaparib
CDK12 E1024*	Olaparib
CDK12 E647Kfs*8	Olaparib
CDK12 E72fs	Olaparib
CDK12 E928fs	Olaparib
CDK12 F89Sfs*3	Olaparib
CDK12 G879V	Olaparib
CDK12 G909R	Olaparib
CDK12 H111fs	Olaparib
CDK12 inact mut	Olaparib
CDK12 K1021*	Olaparib
CDK12 K46fs	Olaparib
CDK12 K756R	Olaparib
CDK12 K975E	Olaparib
CDK12 L122*	Olaparib
CDK12 L996F	Olaparib
CDK12 loss	Olaparib
CDK12 P335fs	Olaparib
CDK12 P58fs	Olaparib
CDK12 P683Qfs*70	Olaparib
CDK12 Q602*	Olaparib
CDK12 Q944*	Olaparib
CDK12 R204fs	Olaparib
CDK12 R271*	Olaparib
CDK12 R701*	Olaparib
CDK12 R882L	Olaparib
CDK12 S133Kfs*24	Olaparib
CDK12 S343fs	Olaparib
CDK12 S587Ffs*54	Olaparib
CDK12 S62fs	Olaparib
CDK12 S785fs	Olaparib
CDK12 T212fs	Olaparib
CDK12 V387*	Olaparib
CDK12 W719*	Olaparib
CDK12 Y279*	Olaparib
CDK12 Y319fs	Olaparib
CDK12 Y901C	Olaparib

Showing 1 to 39 of 39 entries

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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
CDK12	NCBI	CRK7\|CRKR\|CRKRS		CDK12, cyclin dependent kinase 12, is a key regulator of transcription elongation, regulates the expression of genes involved in DNA repair, and is required for the maintenance of genomic stability (PMID: 24554720; PMID: 22012619). Loss and/or inactivation of CDK12 has been commonly observed in many solid tumor types, including prostate (PMID: 29906450, PMID: 31640893), breast, ovarian, endometrial, uterine (PMID: 30104286), and is a likely tumor suppressor (PMID: 30319007).	Tumor suppressor

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Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
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Showing 1 to 26 of 26 entries

Gene	Variant	Impact	Protein Effect	Variant Description
CDK12	K46fs	frameshift	loss of function - predicted	CDK12 K46fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 46 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). K46fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of K46 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	P58fs	frameshift	loss of function - predicted	CDK12 P58fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 58 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). P58fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of P58 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	S62fs	frameshift	loss of function - predicted	CDK12 S62fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 62 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). S62fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of S62 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	E72fs	frameshift	loss of function - predicted	CDK12 E72fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 72 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). E72fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of E72 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	A88fs	frameshift	loss of function - predicted	CDK12 A88fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 88 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). A88fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of A88 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	F89Sfs*3	frameshift	loss of function - predicted	CDK12 F89Sfs3 indicates a shift in the reading frame starting at amino acid 89 and terminating 3 residues downstream causing a premature truncation of the 1490 amino acid Cdk12 protein (UniProt.org). F89Sfs3 has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of F89 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	H111fs	frameshift	loss of function - predicted	CDK12 H111fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 111 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). H111fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of H111 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	L122*	nonsense	loss of function - predicted	CDK12 L122* results in a premature truncation of the Cdk12 protein at amino acid 122 of 1490 (UniProt.org). L122* has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of L122 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	S133Kfs*24	frameshift	loss of function - predicted	CDK12 S133Kfs24 indicates a shift in the reading frame starting at amino acid 133 and terminating 24 residues downstream causing a premature truncation of the 1490 amino acid Cdk12 protein (UniProt.org). S133Kfs24 has not been characterized, however, due to the effects of other truncation mutations downstream of S133 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	R204fs	frameshift	loss of function - predicted	CDK12 R204fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 204 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). R204fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of R204 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	T212fs	frameshift	loss of function - predicted	CDK12 T212fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 212 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). T212fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of T212 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	R271*	nonsense	loss of function - predicted	CDK12 R271* results in a premature truncation of the Cdk12 protein at amino acid 271 of 1490 (UniProt.org). R271* has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of R271 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	Y279*	nonsense	loss of function - predicted	CDK12 Y279* results in a premature truncation of the Cdk12 protein at amino acid 279 of 1490 (UniProt.org). Y279* has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of Y279 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	Y319fs	frameshift	loss of function - predicted	CDK12 Y319fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 319 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). Y319fs has not been characterized, however, due to the effects of other truncation mutations downstream of Y319 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	P335fs	frameshift	loss of function - predicted	CDK12 P335fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 335 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). P335fs has not been characterized, however, due to the effects of truncation mutations downstream of P335 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	S343fs	frameshift	loss of function - predicted	CDK12 S343fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 343 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). S343fs has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of S343 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	S587Ffs*54	frameshift	loss of function - predicted	CDK12 S587Ffs54 indicates a shift in the reading frame starting at amino acid 587 and terminating 54 residues downstream causing a premature truncation of the 1490 amino acid Cdk12 protein (UniProt.org). S587Ffs54 has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of S587 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	Q602*	nonsense	loss of function - predicted	CDK12 Q602* results in a premature truncation of the Cdk12 protein at amino acid 602 of 1490 (UniProt.org). Q602* has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of Q602 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	E647Kfs*8	frameshift	loss of function - predicted	CDK12 E647Kfs8 indicates a shift in the reading frame starting at amino acid 647 and terminating 8 residues downstream causing a premature truncation of the 1490 amino acid Cdk12 protein (UniProt.org). E647Kfs8 has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of E647 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	P683Qfs*70	frameshift	loss of function - predicted	CDK12 P683Qfs70 indicates a shift in the reading frame starting at amino acid 683 and terminating 70 residues downstream causing a premature truncation of the 1490 amino acid Cdk12 protein (UniProt.org). P683Qfs70 has not been biochemically characterized, however, due to the effects of other truncation mutations downstream of P683 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	K756R	missense	loss of function	CDK12 K756R lies within the protein kinase domain of the Cdk12 protein (UniProt.org). K756R results in decreased Cdk12 kinase activity in an in vitro assay and results in decreased homologous repair as demonstrated by failure to restore Rad51 foci formation in Cdk12-depleted cells in culture (PMID: 24554720).
CDK12	S785fs	frameshift	loss of function - predicted	CDK12 S785fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 785 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). S785fs has not been biochemically characterized, however, due to the effects of truncation mutations downstream of S785 (PMID: 24554720, PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
CDK12	D877N	missense	loss of function	CDK12 D877N lies within the protein kinase domain of the Cdk12 protein (UniProt.org). D877N confers a loss of function to Cdk12 as demonstrated by loss of kinase activity in in vitro assays (PMID: 24662513, PMID: 24554720), and decreased transcriptional activity as a chimeric protein in a luciferase assay (PMID: 25712099).
CDK12	R882L	missense	loss of function - predicted	CDK12 R882L lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R882L results in decreased Cdk12-mediated transcriptional activation, downregulation of DNA damage response genes (PMID: 25712099), and decreased kinase activity in cultured cells (PMID: 25712099) and an in vitro assay (PMID: 24554720), but induces proliferation similar to wild-type Cdk12 in one of two tested cell lines in culture (PMID: 29533785), and therefore is predicted to lead to a loss of Cdk12 protein function.
CDK12	G909R	missense	loss of function	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).
CDK12	E928fs	frameshift	loss of function	CDK12 E928fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 928 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). E928fs confers a loss of function to the Cdk12 protein as demonstrated by an inability to interact with CycK in vitro and reduced homologous recombination repair activity in cell culture (PMID: 25712099), and loss of kinase activity in an in vitro assay (PMID: 24554720).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CDK12 dec exp	ovarian cancer	sensitive	Veliparib	Preclinical - Cell culture	Actionable	In a preclinical study, the depletion of CDK12 in an ovarian cancer cell line by siRNAs resulted in the depletion of BRCA1 and sensitized the cells to the cross-linking agents Alkeran (melphalan), Platinol (cisplatin), and the PARP inhibitor, Veliparib (ABT-888) (PMID: 24554720).	24554720
CDK12 dec exp	ovarian cancer	sensitive	Cisplatin	Preclinical	Actionable	In a preclinical study, the depletion of CDK12 in an ovarian cancer cell line by siRNAs resulted in the depletion of BRCA1 and sensitized the cells to the cross-linking agents Alkeran (melphalan), Platinol (cisplatin), and the PARP inhibitor veliparib (ABT-888) (PMID: 24554720).	24554720
CDK12 dec exp	ovarian cancer	sensitive	Melphalan	Preclinical	Actionable	In a preclinical study, the depletion of CDK12 in an ovarian cancer cell line by siRNAs resulted in the depletion of BRCA1 and sensitized the cells to the cross-linking agents Alkeran (melphalan), Platinol (cisplatin), and the PARP inhibitor veliparib (ABT-888) (PMID: 24554720).	24554720

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