ASPA

Chr 17AR

aspartoacylase

Also known as: ACY2, ASP

NCBI Gene: 443ENSG00000108381UniProt: P45381

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]

Primary Disease Associations & Inheritance

Canavan diseaseMIM #271900
AR
574
ClinVar variants
217
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— ASPA
🧬
Gene-Disease Validity (ClinGen)
Canavan disease · 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.
📋
ClinVar Variants
217 Pathogenic / Likely Pathogenic· 146 VUS of 574 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.10LOEUF
pLI 0.000
Z-score 1.33
OE 0.59 (0.33–1.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.48Z-score
OE missense 0.90 (0.79–1.03)
154 obs / 171.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.33–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.79–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 7 / 12.0Missense obs/exp: 154 / 171.6Syn Z: 0.40

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic102
Likely Pathogenic115
VUS146
Likely Benign183
Benign14
Conflicting14
102
Pathogenic
115
Likely Pathogenic
146
VUS
183
Likely Benign
14
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
30
8
64
0
102
Likely Pathogenic
47
49
18
1
115
VUS
0
102
36
8
146
Likely Benign
0
5
57
121
183
Benign
0
1
13
0
14
Conflicting
—14
Total77165188130574

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASPA · protein map & ClinVar variants

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

Gene2Phenotype Curations

ASPA-related Canavan disease

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ASPARTOACYLASE; ASPA
MIM #608034 · *

Canavan disease

MIM #271900

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ASPA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Measures of preoperative anxiety: Part two.
Nowicka-Sauer K et al.·Anaesthesiol Intensive Ther
2024Review
Aspartoacylase suppresses prostate cancer progression by blocking LYN activation.
Weng H et al.·Mil Med Res
2023
Leukodystrophies with astrocytic dysfunction.
Rodriguez D·Handb Clin Neurol
2013Review
Non-genetic therapeutic approaches to Canavan disease.
Roscoe RB et al.·J Neurol Sci
2016Review
Urine N-Acetylaspartate Distinguishes Phenotypes in Canavan Disease.
Nagy A et al.·Hum Gene Ther
2024
The Purification of Human Carboxypeptidase O.
Zhang X·Stud Health Technol Inform
2023
Canavan disease: an Arab scenario.
Zayed H·Gene
2015Review
Canavan disease: clinical features and recent advances in research.
Hoshino H et al.·Pediatr Int
2014Review
Oligodendrocyte-targeted adeno-associated virus gene therapy for Canavan disease in children: a phase 1/2 trial.
Leone P et al.·Nat Med
2025Clinical trial
Premature senescence of T-cell subsets in axial spondyloarthritis.
Fessler J et al.·Ann Rheum Dis
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Canavan Disease

A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial)

RECRUITING
NCT04998396Phase PHASE1, PHASE2Aspa TherapeuticsStarted 2021-09-08
AAV9 BBP-812
Canavan Disease

Natural History Study of Patients With Canavan Disease (CANinform Study)

ACTIVE NOT RECRUITING
NCT04126005Aspa TherapeuticsStarted 2019-10-10
Canavan Disease

rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease

ENROLLING BY INVITATION
NCT04833907Phase PHASE1, PHASE2Myrtelle Inc.Started 2021-04-01
rAAV-Olig001-ASPALevetiracetamPrednisone
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08

External Resources

Links to major genomics databases and tools