ASPA

Chr 17AR

aspartoacylase

Also known as: ACY2, ASP

NCBI Gene: 443 ENSG00000108381 UniProt: P45381 OMIM: 608034

The protein catalyzes the hydrolysis of N-acetyl-L-aspartic acid to aspartate and acetate, which is essential for maintaining white matter in the brain. Mutations cause Canavan disease, an autosomal recessive leukodystrophy. The pathogenic mechanism involves loss of enzyme function leading to toxic accumulation of N-acetyl-L-aspartic acid in the brain.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes an enzyme that catalyzes the conversion of N-acetyl_L-aspartic acid (NAA) to aspartate and acetate. NAA is abundant in the brain where hydrolysis by aspartoacylase is thought to help maintain white matter. This protein is an NAA scavenger in other tissues. Mutations in this gene cause Canavan disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Canavan diseaseMIM #271900

Clinical highlights

Management implications

ASPA has therapies in development

Gene-disease validity (ClinGen)

Canavan disease · 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

1.10

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ASPA

Authoritative clinical overview · Recommended first read

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rAAV-ASPA (oligodendrocyte-tropic) programs
AAV gene therapyPhase 1/2
Deliver ASPA to restore aspartoacylase.
Delivery: One-time IV / intracerebroventricular

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov