ASAH1

Chr 8AR

N-acylsphingosine amidohydrolase 1

Also known as: AC, ACDase, ASAH, PHP, PHP32, SMAPME

NCBI Gene: 427 ENSG00000104763 UniProt: Q13510 OMIM: 613468

The protein functions as a lysosomal ceramidase that hydrolyzes ceramides into sphingosine and fatty acids, regulating bioactive sphingolipid levels that control cellular processes including proliferation, apoptosis, and differentiation. Mutations cause two autosomal recessive disorders: Farber lipogranulomatosis (a lysosomal storage disorder) and spinal muscular atrophy with progressive myoclonic epilepsy (affecting neuromuscular and neurological systems). The gene is highly constrained against loss-of-function variants (LOEUF 1.18), reflecting its essential cellular role.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the acid ceramidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. Processing of this preproprotein generates alpha and beta subunits that heterodimerize to form the mature lysosomal enzyme, which catalyzes the degradation of ceramide into sphingosine and free fatty acid. This enzyme is overexpressed in multiple human cancers and may play a role in cancer progression. Mutations in this gene are associated with the lysosomal storage disorder, Farber lipogranulomatosis, and a neuromuscular disorder, spinal muscular atrophy with progressive myoclonic epilepsy. [provided by RefSeq, Oct 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Farber lipogranulomatosisMIM #228000

Spinal muscular atrophy with progressive myoclonic epilepsyMIM #159950

Clinical highlights

Gene-disease validity (ClinGen)

ASAH1-related sphingolipidosis · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ASAH1