Pathogenic variants in the HCFC1 gene, which encodes a transcriptional cofactor, cause cblX syndrome, intellectual disability, or partial focal epilepsy. HCFC1 encodes a multi-domain precursor protein that undergoes proteolytic cleavage to produce N- and C-terminal fragments that interact non-covalently. Pathogenic variants in the N-terminal kelch domain cause cblX syndrome with high penetrance and severity. However, pathogenic variants in the proteolytic cleavage domain cause focal epilepsy,…
