DENND4C
Chr 9DENN domain containing 4C
Also known as: C9orf55, C9orf55B, RAB10GEF, bA513M16.3
The protein functions as a guanine nucleotide exchange factor that activates RAB10 and promotes insulin-stimulated glucose transporter delivery to the plasma membrane. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, which presents in early infancy with severe epilepsy, developmental delay, and progressive microcephaly. The gene shows high intolerance to loss-of-function variation, indicating that complete protein loss is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
DENND4C · 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