ASAH1

Chr 8AR

N-acylsphingosine amidohydrolase 1

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.182 OMIM phenotypes
Clinical SummaryASAH1
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Gene-Disease Validity (ClinGen)
ASAH1-related sphingolipidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 0.85
OE 0.82 (0.581.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.21Z-score
OE missense 1.42 (1.291.56)
310 obs / 218.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.82 (0.581.18)
00.351.4
Missense OE1.42 (1.291.56)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 21 / 25.6Missense obs/exp: 310 / 218.2Syn Z: -0.05

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ASAH1 · 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.

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Clinical Literature
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