ASPA

Chr 17AR

aspartoacylase

Also known as: ACY2, ASP

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.101 OMIM phenotype
Clinical SummaryASPA
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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.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.33
OE 0.59 (0.331.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.48Z-score
OE missense 0.90 (0.791.03)
154 obs / 171.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.331.10)
00.351.4
Missense OE0.90 (0.791.03)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 7 / 12.0Missense obs/exp: 154 / 171.6Syn Z: 0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveASPA-related Canavan diseaseLOFAR

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

DN
0.6358th %ile
GOF
0.4382th %ile
LOF
0.3067th %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

ASPA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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