Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes.

ABSTRACT: Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells. We find that extremes of SETBP1 protein dose reciprocally influence important signalling molecules such as AK

SUBMITTER: Antonyan L 

PROVIDER: S-EPMC11973901 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature