DENND3
Chr 8DENN domain containing 3
The DENND3 protein functions as a guanine nucleotide exchange factor that activates RAB12, regulating autophagy in response to starvation and controlling protein transport from recycling endosomes to lysosomes. Mutations cause neurodevelopmental disorders with intellectual disability, though the inheritance pattern has not been clearly established. The gene shows minimal constraint against loss-of-function variants (very low pLI score), suggesting tolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
290 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 | 52 | 0 | 52 |
Likely Pathogenic | 1 | 0 | 3 | 0 | 4 |
VUS | 0 | 167 | 3 | 2 | 172 |
Likely Benign | 0 | 14 | 0 | 2 | 16 |
Benign | 0 | 3 | 3 | 6 | 12 |
Conflicting | — | 1 | |||
| Total | 1 | 184 | 61 | 10 | 257 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DENND3 · 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