Heritability and Transcriptional Impact of JAK3, STAT5A and STAT6 Variants in a Tyrolean Family.

ABSTRACT: The Janus Kinase (JAK) and Signal Transducers and Activators of Transcription (STAT) pathways regulate a range of biological processes, including immune response and hematopoiesis. While a major research focus has been on somatic human mutations in disease, less is known about the heritability of germline variants and their physiological impact. This study addresses an important issue in population genetics: the context-dependent effects and incomplete penetrance of rare genetic variants in immune pathways. Here we identify the rare JAK3^P151R, JAK3^R925S, STAT5A^V494L, and STAT6^Q633H variants in an extended family spanning three generations, integrate in silico analyses and AlphaFold 3 structural predictions, and investigate the immune transcriptom

SUBMITTER: Lee HK 

PROVIDER: S-EPMC12842485 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature