BRK1
Chr 3BRICK1 subunit of SCAR/WAVE actin nucleating complex
Also known as: C3orf10, HSPC300, MDS027, hHBrk1
The protein regulates actin and microtubule organization as part of the WAVE complex that activates the Arp2/3 complex and is required for BDNF-NTRK2 endocytic trafficking and signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with brain atrophy, presenting in infancy with seizures, developmental delays, and progressive brain volume loss. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.785).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
BRK1 · 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