Molecular characteristics

BRAT1 related disorder is transmitted in an autosomal recessive manner. The vast majority of pathogenic variants reported in association with BRAT1 related disorder have been compound heterozygous variants, involving a combination of frameshift, missense, and splice site variants.

Suspected pathophysiological mechanisms of cellular dysfunction include impact on DNA repair, apoptosis, cell growth, and mitochondrial homeostasis. As part of the DNA damage response, BRAT1 interacts with BRCA1 (tumour suppressor breast cancer 1, early onset), ATM (ataxia telangiectasia mutated), and DNA-PKcs (DNA-dependent protein kinase, catalytic subunit). In addition to DNA repair, BRAT1 modulates pathways involved in apoptosis and cell growth. Finally, cells missing BRAT1 demonstrate evidence of mitochondrial dysfunction.