CDK9

Chr 9

cyclin dependent kinase 9

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

CDK9 encodes a cyclin-dependent kinase that phosphorylates RNA polymerase II and other proteins to regulate transcriptional elongation, forming the P-TEFb complex essential for productive gene transcription. Mutations cause autosomal dominant developmental delay, seizures, and dysmorphic features with onset in early childhood. The gene is not highly constrained against loss-of-function variants, suggesting the disorder may involve altered protein function rather than simple protein loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.95
Clinical SummaryCDK9
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 35 VUS of 96 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.70
OE 0.55 (0.330.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.14Z-score
OE missense 0.61 (0.530.70)
145 obs / 237.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.55 (0.330.95)
00.351.4
Missense OE0.61 (0.530.70)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 9 / 16.5Missense obs/exp: 145 / 237.9Syn Z: -2.27
DN
0.74top 25%
GOF
0.6053th %ile
LOF
0.3455th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

96 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic2
VUS35
Likely Benign8
Benign4
38
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
38
0
38
Likely Pathogenic
0
1
1
0
2
VUS
0
33
2
0
35
Likely Benign
1
0
2
5
8
Benign
0
0
2
2
4
Total13445787

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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