CDK11A

Chr 1

cyclin dependent kinase 11A

Also known as: CDC2L2, CDC2L3, CDK11-p110, CDK11-p46, CDK11-p58, PITSLRE, p58GTA

This gene encodes a cyclin-dependent protein kinase that regulates transcription and pre-mRNA splicing by phosphorylating key components of the spliceosome and RNA polymerase II. CDK11A mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and seizures, with onset in infancy or early childhood. The gene shows minimal tolerance to loss-of-function variants in the general population, indicating it is highly constrained and essential for normal function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
140
P/LP submissions
0%
P/LP missense
1.29
LOEUF
DN
Mechanism· predicted
Clinical SummaryCDK11A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
133 unique Pathogenic / Likely Pathogenic· 137 VUS of 289 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.000
Z-score 0.32
OE 0.94 (0.691.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.83Z-score
OE missense 1.13 (1.041.24)
339 obs / 298.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.94 (0.691.29)
00.351.4
Missense OE1.13 (1.041.24)
00.61.4
Synonymous OE1.36
01.21.6
LoF obs/exp: 27 / 28.8Missense obs/exp: 339 / 298.7Syn Z: -3.12
DN
0.6550th %ile
GOF
0.5563th %ile
LOF
0.4528th %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

289 submitted variants in ClinVar

Classification Summary

Pathogenic125
Likely Pathogenic8
VUS137
Likely Benign10
125
Pathogenic
8
Likely Pathogenic
137
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
125
0
125
Likely Pathogenic
0
0
8
0
8
VUS
1
116
20
0
137
Likely Benign
0
3
1
6
10
Benign
0
0
0
0
0
Total11191546280

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

View in ClinVar →

Protein Context — Lollipop Plot

CDK11A · protein map & ClinVar variants

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

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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found