CDK19

Chr 6AD

cyclin dependent kinase 19

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

NCBI Gene: 23097ENSG00000155111UniProt: Q9BWU1OMIM: 614720

CDK19 encodes a component of the Mediator co-activator complex that is required for transcriptional activation of genes by RNA polymerase II. Mutations cause developmental and epileptic encephalopathy 87 through an autosomal dominant inheritance pattern via loss-of-function mechanisms.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.161 OMIM phenotype
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.
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ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 78 VUS of 139 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.03 (0.01–0.16)
0≤0.351.4
Missense OE0.40 (0.35–0.47)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 1 / 29.0Missense obs/exp: 114 / 282.5Syn Z: 0.87
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCDK19-related intellectual disability and epileptic encephalopathyOTHERAD
DN
0.3892th %ile
GOF
0.4085th %ile
LOF
0.79top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.16
DN1 literature citation

Literature Evidence

DNHowever, in vivo functional expression studies in Drosophila showed that the mutant protein localized normally to the perinuclear region in neurons, and that the mutation resulted in a loss-of-function effect acting in a dominant-negative manner.PMID:32330417
LOFQuantitative PCR of the CDK19 transcript from Epstein-Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene.PMID:20563892

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

139 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic6
VUS78
Likely Benign14
Conflicting2
21
Pathogenic
6
Likely Pathogenic
78
VUS
14
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
2
0
6
VUS
4
60
14
0
78
Likely Benign
0
2
3
9
14
Benign
0
0
0
0
0
Conflicting
—2
Total470369121

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients