DPYSL4
Chr 10dihydropyrimidinase like 4
Also known as: CRMP3, DRP-4, ULIP4
The protein is necessary for signaling by class 3 semaphorins and subsequent cytoskeleton remodeling, playing a role in axon guidance, neuronal growth cone collapse and cell migration. Mutations in DPYSL4 cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, presenting in infancy with seizures, severe developmental delay, and progressive microcephaly. The gene shows moderate constraint against loss-of-function variants, and the condition primarily affects the central nervous system with early onset neurological manifestations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
DPYSL4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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