ACY1

Chr 3AR

aminoacylase 1

Also known as: ACY-1, ACY1D, HEL-S-5

ACY1 encodes aminoacylase-1, a cytosolic zinc-binding enzyme that hydrolyzes N-acetylated and N-formylated amino acids into free amino acids and carboxylates, functioning in amino acid salvage pathways. Biallelic mutations cause aminoacylase-1 deficiency, an autosomal recessive metabolic disorder characterized by central nervous system defects and increased urinary excretion of N-acetylated amino acids. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Aminoacylase 1 deficiencyMIM #609924
AR
UniProtAminoacylase-1 deficiency
0
Active trials
8
Pubs (1 yr)
31
P/LP submissions
5%
P/LP missense
1.06
LOEUF
LOF
Mechanism· G2P
Clinical SummaryACY1
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Gene-Disease Validity (ClinGen)
aminoacylase 1 deficiency · 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
21 unique Pathogenic / Likely Pathogenic· 107 VUS of 209 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.000
Z-score 1.33
OE 0.70 (0.471.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.10Z-score
OE missense 0.98 (0.881.09)
237 obs / 241.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.471.06)
00.351.4
Missense OE0.98 (0.881.09)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 16 / 22.9Missense obs/exp: 237 / 241.2Syn Z: -0.44
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveACY1-related aminoacylase 1 deficiencyLOFAR

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

DN
0.7033th %ile
GOF
0.6541th %ile
LOF
0.2776th %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

209 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic5
VUS107
Likely Benign57
Benign12
Conflicting11
16
Pathogenic
5
Likely Pathogenic
107
VUS
57
Likely Benign
12
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
10
0
16
Likely Pathogenic
4
0
1
0
5
VUS
5
87
14
1
107
Likely Benign
1
7
19
30
57
Benign
0
1
9
2
12
Conflicting
11
Total15965333208

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

View in ClinVar →

Protein Context — Lollipop Plot

ACY1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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