Bi-allelic loss-of-function variants in TMEM63B cause syndromic surfactant dysfunction disorder.

ABSTRACT: Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two re

SUBMITTER: Chan SH 

PROVIDER: S-EPMC13310454 | biostudies-literature | 2026 Jul

REPOSITORIES: biostudies-literature