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Gene Symbol CDK12
Synonyms CRK7 | CRKR | CRKRS
Gene Description 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).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1117E missense unknown CDK12 A1117E does not lie within any known functional domains of the Cdk12 protein (UniProt.org). A1117E has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
A1117V missense unknown CDK12 A1117V does not lie within any known functional domains of the Cdk12 protein (UniProt.org). A1117V has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of A88 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
amp none no effect CDK12 amplification indicates an increased number of copies of the CDK12 gene. However, the mechanism causing the increase is unspecified.
D502Y missense unknown CDK12 D502Y does not lie within any known functional domains of the Cdk12 protein (UniProt.org). D502Y has been identified in sequencing studies (PMID: 23303603, PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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).
D918N missense unknown CDK12 D918N lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). D918N has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
dec exp none no effect CDK12 dec exp indicates decreased expression of the Cdk12 protein. However, the mechanism causing the decreased expression is unspecified.
del deletion loss of function CDK12 del indicates a deletion of the CDK12 gene.
E1024* nonsense loss of function CDK12 E1024* results in a premature truncation of the Cdk12 protein at amino acid 1024 of 1490 (UniProt.org). E1024* confers a loss of function to the Cdk12 protein as demonstrated by decreased binding to CycK in cell culture and reduced kinase activity in an in vitro assay (PMID: 25712099).
E1171Q missense unknown CDK12 E1171Q does not lie within any known functional domains of the Cdk12 protein (UniProt.org). E1171Q has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
E1327D missense unknown CDK12 E1327D does not lie within any known functional domains of the Cdk12 protein (UniProt.org). E1327D has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of E72 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
E774K missense unknown CDK12 E774K lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). E774K has been identified in the scientific literature (PMID: 30487607), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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).
F89Sfs*3 frameshift loss of function - predicted CDK12 F89Sfs*3 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). F89Sfs*3 has not been biochemically characterized, however, due to the effects of truncation mutations downstream of F89 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
F986L missense unknown CDK12 F986L lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). F986L has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
G677D missense unknown CDK12 G677D lies within the proline-rich motif region of the Cdk12 protein (PMID: 22512864). G677D has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
G879V missense loss of function - predicted CDK12 G879V lies within the protein kinase domain of the Cdk12 protein (UniProt.org). G879V fails to rescue a DNA damage-induced decrease in cell viability in cells lacking Cdk12 in culture (PMID: 30617155), and therefore, is predicted to lead to a loss of Cdk12 protein function.
G909E missense unknown CDK12 G909E lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). G909E has been identified in the scientific literature (PMID: 30487607), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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).
G923V missense unknown CDK12 G923V lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). G923V has been identified in sequencing studies (PMID: 29906450), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of H111 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
H999Y missense unknown CDK12 H999Y lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). H999Y has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
I1131V missense unknown CDK12 I1131V does not lie within any known functional domains of the Cdk12 protein (UniProt.org). I1131V has been identified in sequencing studies (PMID: 26787835), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
inact mut unknown loss of function CDK12 inact mut indicates that this variant results in a loss of function of the Cdk12 protein. However, the specific amino acid change has not been identified.
K1422N missense unknown CDK12 K1422N does not lie within any known functional domains of the Cdk12 protein (UniProt.org). K1422N has not been characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
K208T missense unknown CDK12 K208T lies within an arginine/serine-rich motif region of the Cdk12 protein (PMID: 22512864). K208T has been identified in sequencing studies (PMID: 24690483), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
K211T missense unknown CDK12 K211T lies within an arginine/serine-rich motif region of the Cdk12 protein (PMID: 22512864). K211T has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of K46 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
K51R missense unknown CDK12 K51R does not lie within any known functional domains of the Cdk12 protein (UniProt.org). K51R has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
K756R missense loss of function CDK12 K756R lies within the protein kinase domain of the Cdk12 protein (UniProt.org). K756R results in a kinase dead Cdk12 protein (PMID: 24554720).
K852Q missense unknown CDK12 K852Q lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). K852Q has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
K853N missense unknown CDK12 K853N lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). K853N has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
K932N missense unknown CDK12 K932N lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). K932N has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
K975E missense loss of function CDK12 K975E lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). K975E results in decreased transcriptional activation by Cdk12 and reduced expression of DNA damage response genes in cultured cells (PMID: 25712099).
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 truncation mutations downstream of L122 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
L926I missense no effect CDK12 L926I lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). L926I has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Oct 2015).
L996F missense loss of function CDK12 L996F lies within the protein kinase domain of the Cdk12 protein (UniProt.org). L996F results in loss of Cdk12 binding to CycK, decreased Cdk12 kinase activity in an in vitro assay, and reduced transcriptional activity in a reporter assay (PMID: 25712099).
loss unknown loss of function CDK12 loss indicates loss of the CDK12 gene, mRNA, and protein.
mutant unknown unknown CDK12 mutant indicates an unspecified mutation in the CDK12 gene.
P1060L missense unknown CDK12 P1060L does not lie within any known functional domains of the Cdk12 protein (UniProt.org). P1060L has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
P1275L missense unknown CDK12 P1275L lies within the proline-rich motif region of the Cdk12 protein (PMID: 22512864). P1275L has been identified in the scientific literature (PMID: 26979391, PMID: 29642553, PMID: 26343384), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
P1325S missense unknown CDK12 P1325S does not lie within any known functional domains of the Cdk12 protein (UniProt.org). P1325S has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
P250H missense unknown CDK12 P250H does not lie within any known functional domains of the Cdk12 protein (UniProt.org). P250H has been identified in sequencing studies (PMID: 27573823), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
P526H missense unknown CDK12 P526H lies within the proline-rich motif region of the Cdk12 protein (PMID: 22512864). P526H has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
P586S missense unknown CDK12 P586S lies within the proline-rich motif region of the Cdk12 protein (PMID: 22512864). P586S has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of P58 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
P653H missense unknown CDK12 P653H lies within the proline-rich motif region of the Cdk12 protein (PMID: 22512864). P653H has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
P961S missense unknown CDK12 P961S lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). P961S has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
positive unknown unknown CDK12 positive indicates the presence of the CDK12 gene, mRNA, and/or protein.
Q1013_L1015del deletion unknown CDK12 Q1013_L1015del results in the deletion of three amino acids in the protein kinase domain of the Cdk12 protein from amino acids 1013 to 1015 (UniProt.org). Q1013_L1015del has been identified in sequencing studies (PMID: 26787835), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
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 truncation mutations downstream of Q602 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
Q944* nonsense loss of function - predicted CDK12 Q944* results in a premature truncation of the Cdk12 protein at amino acid 944 of 1490 (UniProt.org). Q944* has not been characterized however, due to the effects of truncation mutations downstream of Q944 (PMID: 25712099), is predicted to lead to a loss of Cdk12 protein function.
R1008Q missense unknown CDK12 R1008Q lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R1008Q has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R1008W missense unknown CDK12 R1008W lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R1008W has been identified in sequencing studies (PMID: 29338072, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R1067* nonsense unknown CDK12 R1067* results in a premature truncation of the Cdk12 protein at amino acid 1067 of 1490 (UniProt.org). R1067* has been identified in sequencing studies (PMID: 25712099, PMID: 27124486), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
R197L missense unknown CDK12 R197L does not lie within any known functional domains of the Cdk12 protein (UniProt.org). R197L has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
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 truncation mutations downstream of R271 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
R378C missense unknown CDK12 R378C lies within an arginine/serine-rich motif region of the Cdk12 protein (PMID: 22512864). R378C has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R722C missense unknown CDK12 R722C lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R722C has not been characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R779C missense unknown CDK12 R779C lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R779C has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R779H missense unknown CDK12 R779H lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R779H has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R858W missense unknown CDK12 R858W lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R858W has been identified in the scientific literature (PMID: 30487607, PMID: 26000489), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R882L missense loss of function CDK12 R882L lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R882L results in decreased Cdk12 kinase activity, decreased Cdk12-mediated transcriptional activation, down-regulation of DNA damage response genes in cultured cells (PMID: 25712099), and in one of two cell lines, induced similar cell proliferation and cell viability as wild-type Cdk12 (PMID: 29533785).
R890H missense unknown CDK12 R890H lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R890H has been identified in sequencing studies (PMID: 25151357), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R902P missense unknown CDK12 R902P lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). R902P has not been characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
R983_E984delinsQ indel unknown CDK12 R983_E984delinsQ results in a deletion of an arginine (R) and glutamate (E) in the protein kinase domain of the Cdk12 protein from aa 983 to aa 984, combined with the insertion of a glutamine (Q) at the same location (UniProt.org). R983_E984delinsQ has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
S192Y missense unknown CDK12 S192Y lies within an arginine/serine-rich motif region of the Cdk12 protein (PMID: 22512864). S192Y has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of S343 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
S475Y missense unknown CDK12 S475Y does not lie within any known functional domains of the Cdk12 protein (UniProt.org). S475Y has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
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 truncation mutations downstream of S62 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
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 result in a loss of Cdk12 protein function.
S863L missense unknown CDK12 S863L lies within the protein kinase domain of the Cdk12 protein (UniProt.org). S863L has been identified in sequencing studies (PMID: 26787835), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
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 truncation mutations downstream of T212 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
V1055G missense unknown CDK12 V1055G does not lie within any known functional domains of the Cdk12 protein (UniProt.org). V1055G has not been characterized in the scientific literature and therefore, its effect on Cdk12 protein function is unknown (PubMed, Feb 2021).
V39L missense unknown CDK12 V39L does not lie within any known functional domains of the Cdk12 protein (UniProt.org). V39L has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Mar 2021).
V919F missense unknown CDK12 V919F lies within the protein kinase domain of the Cdk12 protein (UniProt.org). V919F has been identified in sequencing studies (PMID: 26787835), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
W1459fs frameshift unknown CDK12 W1459fs results in a change in the amino acid sequence of the Cdk12 protein beginning at aa 1459 of 1490, likely resulting in premature truncation of the functional protein (UniProt.org). W1459fs has been identified in sequencing studies (PMID: 29367197), but has not been biochemically characterized and therefore, its effect on Cdk12 protein function is unknown (PubMed, Dec 2020).
W719* nonsense loss of function CDK12 W719* results in a premature truncation of the Cdk12 protein at amino acid 719 of 1490 (UniProt.org). W719* confers a loss of function to the Cdk12 protein as demonstrated by an inability to interact with CycK in vitro (PMID: 25712099).
wild-type none no effect Wild-type CDK12 indicates that no mutation has been detected within the CDK12 gene.
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 truncation mutations downstream of Y279 (PMID: 24554720, PMID: 25712099), is predicted to result in a loss of Cdk12 protein function.
Y901C missense loss of function CDK12 Y901C lies within the protein kinase domain of the Cdk12 protein (PMID: 22512864). Y901C results in decreased Cdk12 kinase activity, loss of CycK binding, decreased Cdk12-mediated transcriptional activation and down-regulation of DNA damage response genes in cultured cells (PMID: 25712099), and in one of two cell lines, Y901C increased cell proliferation and cell viability as compared to wild-type Cdk12 (PMID: 29533785).