ACER3

Chr 11AR

alkaline ceramidase 3

Also known as: APHC, PHCA, PLDECO

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.391 OMIM phenotype
Clinical SummaryACER3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.875
Z-score 3.52
OE 0.15 (0.070.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.80Z-score
OE missense 0.57 (0.470.68)
77 obs / 136.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.070.39)
00.351.4
Missense OE0.57 (0.470.68)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 3 / 20.0Missense obs/exp: 77 / 136.1Syn Z: 0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongACER3-related leukodystrophyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.6151th %ile
LOF
0.3260th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACER3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →