DENND5B
Chr 12DENN domain containing 5B
The protein functions as a guanine nucleotide exchange factor that activates RAB39A and RAB39B by promoting GDP to GTP exchange. Mutations cause autosomal recessive intellectual disability with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variation (pLI = 1.0, LOEUF = 0.155), indicating that complete loss of protein function is likely not tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
ClinVar Variant Classifications
241 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 | 29 | 0 | 29 |
Likely Pathogenic | 0 | 1 | 3 | 0 | 4 |
VUS | 4 | 153 | 10 | 0 | 167 |
Likely Benign | 0 | 13 | 0 | 8 | 21 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 4 | 167 | 42 | 8 | 221 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DENND5B · 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