CDK5
Chr 7ARcyclin dependent kinase 5
Also known as: LIS7, PSSALRE
This gene encodes a proline-directed serine/threonine kinase that functions in neuronal migration, synaptic plasticity, and cytoskeletal organization by phosphorylating key proteins involved in these processes. Mutations cause autosomal recessive lissencephaly-7 with cerebellar hypoplasia, a severe brain malformation disorder. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.562) and has high expression in postmitotic central nervous system neurons.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
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
171 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 70 | 0 | 71 |
Likely Pathogenic | 0 | 1 | 4 | 0 | 5 |
VUS | 0 | 12 | 9 | 0 | 21 |
Likely Benign | 0 | 0 | 20 | 28 | 48 |
Benign | 0 | 0 | 10 | 1 | 11 |
Conflicting | — | 1 | |||
| Total | 1 | 13 | 113 | 29 | 157 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CDK5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools