CDK19

Chr 6AD

cyclin dependent kinase 19

Also known as: CDC2L6, CDK11, DEE87, EIEE87, bA346C16.3

NCBI Gene: 23097ENSG00000155111UniProt: Q9BWU1

This gene encodes a protein that is one of the components of the Mediator co-activator complex. The Mediator complex is a multi-protein complex required for transcriptional activation by DNA binding transcription factors of genes transcribed by RNA polymerase II. The protein encoded by this gene is similar to cyclin-dependent kinase 8 which can also be a component of the Mediator complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 87MIM #618916
AD
118
ClinVar variants
26
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CDK19
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 77 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.16LOEUF
pLI 1.000
Z-score 4.82
OE 0.03 (0.01–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
3.56Z-score
OE missense 0.40 (0.35–0.47)
114 obs / 282.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.03 (0.01–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.35–0.47)
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.0.89
0≤1.21.6
LoF obs/exp: 1 / 29.0Missense obs/exp: 114 / 282.5Syn Z: 0.87

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic5
VUS77
Likely Benign13
Conflicting2
21
Pathogenic
5
Likely Pathogenic
77
VUS
13
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
17
0
21
Likely Pathogenic
0
4
1
0
5
VUS
2
58
17
0
77
Likely Benign
0
2
3
8
13
Benign
0
0
0
0
0
Conflicting
—2
Total268388118

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

View in ClinVar →

Protein Context — Lollipop Plot

CDK19 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CDK19-related intellectual disability and epileptic encephalopathy

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 87

MIM #618916

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mediator kinase inhibition reverses castration resistance of advanced prostate cancer.
Li J et al.·J Clin Invest
2024
CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia.
Offermann A et al.·Hum Pathol
2021
Identifying Cancers Impacted by CDK8/19.
Roninson IB et al.·Cells
2019
CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants.
Zarate YA et al.·Genet Med
2021
Evodiamine inhibits malignant progression of ovarian cancer cells by regulating lncRNA-NEAT1/miR-152-3p/CDK19 axis.
Mao M et al.·Chem Biol Drug Des
2023
MED12 and CDK8/19 Modulate Androgen Receptor Activity and Enzalutamide Response in Prostate Cancer.
Andolfi C et al.·Endocrinology
2024
Cyclin-dependent kinase 19 upregulation correlates with an unfavorable prognosis in hepatocellular carcinoma.
Cai X et al.·BMC Gastroenterol
2021
A novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms.
Yang S et al.·Cold Spring Harb Mol Case Stud
2021
ISOC1 promotes the proliferation of gastric cancer cells by positively regulating CDK19.
Zhao JQ et al.·Eur Rev Med Pharmacol Sci
2020
Uncovering functional insights into human pathogenic variants in CDK19 using Drosophila models.
Grewal KS et al.·Hum Mol Genet
2026Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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