ASAH1

ASAH1 encodes acid ceramidase, a soluble lysosomal N-terminal nucleophile hydrolase that cleaves ceramide into sphingosine and a free fatty acid at acidic pH. A glycosylated precursor undergoes autocleavage into disulfide-linked alpha and beta subunits, exposing catalytic Cys143 at the beta-subunit N terminus. Mannose-6-phosphate-dependent trafficking delivers the enzyme to the endolysosomal system, where saposin D facilitates access to membrane ceramide. Acid ceramidase shapes cellular ceramide and sphingosine pools; substrate preferences depend on ceramide structure and assay conditions. Cellular studies also support glycosphingolipid deacylation when lysosomal glycosidases are deficient. Secreted and nuclear pools occur in particular settings, including an interaction with the nuclear receptor SF-1 in adrenocortical cells. Pathogenic ASAH1 variants cause a spectrum including Farber disease and spinal muscular atrophy with or without progressive myoclonic epilepsy.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• lysosomal_substrate_accumulation via Spinal Muscular Atrophy-Progressive Myoclonic Epilepsy Syndrome