CDK9

Chr 9

cyclin dependent kinase 9

Also known as: C-2k, CDC2L4, CTK1, PITALRE, TAK

NCBI Gene: 1025ENSG00000136807UniProt: P50750

The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. [provided by RefSeq, Jul 2008]

86
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CDK9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 35 VUS of 86 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.000
Z-score 1.70
OE 0.55 (0.33–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.14Z-score
OE missense 0.61 (0.53–0.70)
145 obs / 237.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.33–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.53–0.70)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.29
0≤1.21.6
LoF obs/exp: 9 / 16.5Missense obs/exp: 145 / 237.9Syn Z: -2.27

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic2
VUS35
Likely Benign8
Benign4
37
Pathogenic
2
Likely Pathogenic
35
VUS
8
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
1
1
0
2
VUS
0
33
2
0
35
Likely Benign
0
0
3
5
8
Benign
0
0
2
2
4
Total03445786

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CDK9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cyclin-dependent kinases.
Malumbres M·Genome Biol
2014Review
PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer.
Wang LY et al.·Annu Rev Pharmacol Toxicol
2025Review
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
AZD4573 Is a Highly Selective CDK9 Inhibitor That Suppresses MCL-1 and Induces Apoptosis in Hematologic Cancer Cells.
Cidado J et al.·Clin Cancer Res
2020
BRD4 acts as a transcriptional repressor of RhoB to inhibit terminal erythropoiesis.
Chen Y et al.·J Hematol Oncol
2025
Clinical considerations for the design of PROTACs in cancer.
Nieto-Jiménez C et al.·Mol Cancer
2022Review
Disrupting integrator complex subunit INTS6 causes neurodevelopmental disorders and impairs neurogenesis and synapse development.
Peng X et al.·J Clin Invest
2025
CDK9 inhibitors for the treatment of solid tumors.
Mo C et al.·Biochem Pharmacol
2024Review
Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.
Jiménez-Vacas JM et al.·Nat Commun
2025
Unraveling the CDK9/PP2A/ERK Network in Transcriptional Pause Release and Complement Activation in KRAS-mutant Cancers.
Wang Y et al.·Adv Sci (Weinh)
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CDK9 interacts with a RanGTP-Importin-β complex to regulate erythroid enucleation.
Newton LM et al.·J Cell Sci
2026
DualPG-DTA: A Large Language Model-Powered Graph Neural Network Framework for Enhanced Drug-Target Affinity Prediction and Discovery of Novel CDK9 Inhibitors Exhibiting In Vivo Anti-Leukemia Activity.
Chen Y et al.·Adv Sci (Weinh)
2026🔓 Open AccessFunctional
CDK9 Inhibition with enitociclib reveals influence on HERV and LINE RNA abundances in whole blood, T-, and B-Cell lines.
Dopkins N et al.·BMC Med Genomics
2026🔓 Open Access
CDK9-mediated transcriptional activation of NEK7 promotes NLRP3-dependent podocyte Pyroptosis in diabetic kidney disease.
Wang J et al.·Int Immunopharmacol
2026
Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.
van der Noord VE et al.·Cell Oncol (Dordr)
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools