Hh mutants abrogate ligand secretion

Hh signaling is required for a number of developmental processes, and mutations that disrupt the normal processing and biogenesis of Hh ligand can result in neonatal abnormalities. SHH is one of a number of genes that have been associated with the congenital disorder holoprosencephaly, which causes abnormalities in brain and craniofacial development (Roessler et al, 2009; reviewed in Roessler and Muenke, 2011). SHH variants associated with the condition affect the autocatalytic processing of the precursor and dramatically impair the production of the secreted active Hh-Np, abrogating signaling (reviewed in Pan et al, 2013). Aberrant Hh signaling is also associated with gondal dysgenesis syndromes in which palmitoylation of DHH is abrogated by mutation of the acyltransferase HHAT.

Summary from Reactome (R-HSA-5387390), read 2026-09-23.