COMMD6
Chr 13COMM domain containing 6
Also known as: Acrg
COMMD6 encodes a scaffold protein essential for the commander complex that regulates endosomal recycling of transmembrane cargos and inhibits NF-kappa-B activation. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, seizures, and brain abnormalities, with onset in infancy or early childhood. The gene shows moderate tolerance to loss-of-function variants, consistent with recessive inheritance patterns.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
102 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 69 |
Likely Pathogenic | — | — | — | — | 0 |
VUS | — | — | — | — | 15 |
Likely Benign | — | — | — | — | 0 |
Benign | — | — | — | — | 0 |
| Total | — | 84 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
COMMD6 · 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