CDK9

Chr 9

cyclin dependent kinase 9

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

NCBI Gene: 1025 ENSG00000136807 UniProt: P50750 OMIM: 603251

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

217

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.70

OE 0.55 (0.33–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

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?

LoF OE?0.55 (0.33–0.95)

0≤0.351.4

Missense OE?0.61 (0.53–0.70)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 9 / 16.5Missense obs/exp: 145 / 237.9Syn Z: -2.27

Background carrier burden — how many people carry a rare variant somewhere in CDK9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

574 rare PASS variants

Rare truncating (LoF)

1 in 1,200

104 rare PASS variants

Rare synonymous (reference)

1 in 86

344 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDK9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 2,000
South Asian	~43k	1 in 130	1 in 1,200
Remaining (unassigned)	~30k	1 in 91	1 in 2,500
European (Finnish)	~27k	1 in 340	1 in 610
Admixed American	~22k	1 in 170	1 in 520
African / African American	~21k	1 in 120	≈ 1 in 4,500
East Asian	~20k	1 in 86	1 in 2,800
Ashkenazi Jewish	~13k	1 in 570	1 in 1,800
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓