ACER3

Chr 11AR

alkaline ceramidase 3

Also known as: APHC, PHCA, PLDECO

NCBI Gene: 55331 ENSG00000078124 UniProt: Q9NUN7 OMIM: 617036

The ACER3 protein is an endoplasmic reticulum and Golgi ceramidase that hydrolyzes ceramides into sphingosine and fatty acids, regulating sphingolipid metabolism critical for cellular signaling, myelination, and neuronal function. Biallelic mutations cause progressive leukodystrophy with early childhood onset, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.87, LOEUF 0.39), consistent with its essential role in brain sphingolipid homeostasis.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables N-acylsphingosine amidohydrolase activity; calcium ion binding activity; and zinc ion binding activity. Involved in several processes, including myelination; positive regulation of cell population proliferation; and sphingolipid metabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. Biomarker of hepatocellular carcinoma and metabolic dysfunction-associated steatohepatitis. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Leukodystrophy, progressive, early childhood-onsetMIM #617762

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.39

LOEUF

Mechanism· predicted