CDK5R1

Chr 17

cyclin dependent kinase 5 regulatory subunit 1

Also known as: CDK5P35, CDK5R, NCK5A, p23, p25, p35, p35nck5a

The CDK5R1 gene encodes p35, a neuron-specific activator of cyclin-dependent kinase 5 that is essential for neurite outgrowth, cortical lamination, and dendritic spine morphogenesis during central nervous system development. Mutations in CDK5R1 cause lissencephaly and cortical dysplasia-cryptogenic epilepsy syndrome, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function mutations, reflecting its critical role in neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.38
Clinical SummaryCDK5R1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.915
Z-score 2.61
OE 0.00 (0.000.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.91Z-score
OE missense 0.61 (0.520.71)
115 obs / 189.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.38)
00.351.4
Missense OE0.61 (0.520.71)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 0 / 7.9Missense obs/exp: 115 / 189.0Syn Z: -0.63
DN
0.3495th %ile
GOF
0.4283th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.38

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CDK5R1 · 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

No active trials found for this gene.

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Clinical Literature
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