DCUN1D3
Chr 16defective in cullin neddylation 1 domain containing 3
Also known as: 44M2.4, DCNL3, SCCRO3
The protein facilitates neddylation of cullin proteins, which regulates SCF ubiquitin E3 ligase complexes involved in cell cycle progression and DNA damage response. Mutations cause autosomal dominant developmental delay with seizures and dysmorphic features, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants (pLI = 0.87, LOEUF = 0.43), consistent with its essential role in cellular regulation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
58 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 | 0 | 0 | 14 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 31 | 6 | 0 | 37 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 31 | 20 | 0 | 51 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DCUN1D3 · 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