ACY1

Summary

ACY1 (aminoacylase 1, HGNC:177) is a protein-coding gene on chromosome 3p21.2, encoding Aminoacylase-1 (Q03154). Aminoacylase involved in the hydrolysis of N-acetylated and N-formylated amino acids.

This gene encodes a cytosolic, homodimeric, zinc-binding enzyme that catalyzes the hydrolysis of acylated L-amino acids to L-amino acids and an acyl group, and has been postulated to function in the catabolism and salvage of acylated amino acids. This gene is located on chromosome 3p21.1, a region reduced to homozygosity in small-cell lung cancer (SCLC), and its expression has been reported to be reduced or undetectable in SCLC cell lines and tumors. The amino acid sequence of human aminoacylase-1 is highly homologous to the porcine counterpart, and this enzyme is the first member of a new family of zinc-binding enzymes. Mutations in this gene cause aminoacylase-1 deficiency, a metabolic disorder characterized by central nervous system defects and increased urinary excretion of N-acetylated amino acids. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ABHD14A (abhydrolase domain containing 14A) gene, as represented in GeneID:100526760. A related pseudogene has been identified on chromosome 18.

Source: NCBI Gene 95 — RefSeq curated summary.

At a glance

• Gene–disease (curated): aminoacylase 1 deficiency (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 16 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_000666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:177
Approved symbol	ACY1
Name	aminoacylase 1
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000243989
Ensembl biotype	protein_coding
OMIM	104620
Entrez	95

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 32 protein_coding, 14 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000404366, ENST00000464587, ENST00000465121, ENST00000468068, ENST00000469863, ENST00000476351, ENST00000476854, ENST00000490244, ENST00000491318, ENST00000494103, ENST00000496679, ENST00000635797, ENST00000635941, ENST00000636047, ENST00000636358, ENST00000636556, ENST00000636880, ENST00000637034, ENST00000637102, ENST00000637149, ENST00000637199, ENST00000637209, ENST00000637251, ENST00000637349, ENST00000637460, ENST00000637746, ENST00000638077, ENST00000638096, ENST00000638136, ENST00000874798, ENST00000874799, ENST00000874800, ENST00000874801, ENST00000874802, ENST00000874803, ENST00000874804, ENST00000874805, ENST00000874806, ENST00000874807, ENST00000874808, ENST00000874809, ENST00000874810, ENST00000874811, ENST00000874812, ENST00000874813, ENST00000874814, ENST00000874815, ENST00000874816, ENST00000940876, ENST00000940877, ENST00000953766, ENST00000953767, ENST00000953768

RefSeq mRNA: 5 — MANE Select: NM_000666 NM_000666, NM_001198895, NM_001198896, NM_001198897, NM_001198898

CCDS: CCDS2844, CCDS56261, CCDS56262, CCDS56263

Canonical transcript exons

ENST00000636358 — 15 exons

Exon	Start	End
ENSE00001916539	51983535	51983589
ENSE00003473315	51985852	51985946
ENSE00003479638	51987556	51987624
ENSE00003482480	51988524	51988603
ENSE00003516009	51984047	51984158
ENSE00003517215	51986605	51986661
ENSE00003530180	51988911	51989197
ENSE00003542025	51986415	51986504
ENSE00003545013	51987147	51987196
ENSE00003559556	51988766	51988826
ENSE00003663758	51986255	51986331
ENSE00003674351	51985361	51985465
ENSE00003688028	51987309	51987453
ENSE00003688386	51985207	51985271
ENSE00003784254	51986988	51987061

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6872 / max 359.7969, expressed in 1796 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36803	20.2846	1793
36801	1.0229	506
36802	0.2530	112
36804	0.1269	32

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	98.97	gold quality
right lobe of liver	UBERON:0001114	98.92	gold quality
adult mammalian kidney	UBERON:0000082	98.80	gold quality
liver	UBERON:0002107	98.59	gold quality
mucosa of transverse colon	UBERON:0004991	97.99	gold quality
kidney	UBERON:0002113	96.54	gold quality
cortex of kidney	UBERON:0001225	95.63	gold quality
metanephros cortex	UBERON:0010533	94.75	gold quality
small intestine	UBERON:0002108	94.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.24	gold quality
right adrenal gland	UBERON:0001233	93.72	gold quality
right adrenal gland cortex	UBERON:0035827	93.56	gold quality
rectum	UBERON:0001052	93.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.04	gold quality
left adrenal gland	UBERON:0001234	92.81	gold quality
left adrenal gland cortex	UBERON:0035825	92.74	gold quality
transverse colon	UBERON:0001157	92.61	gold quality
right lobe of thyroid gland	UBERON:0001119	92.33	gold quality
adrenal gland	UBERON:0002369	91.90	gold quality
left lobe of thyroid gland	UBERON:0001120	91.47	gold quality
thyroid gland	UBERON:0002046	91.16	gold quality
apex of heart	UBERON:0002098	89.59	gold quality
prostate gland	UBERON:0002367	89.48	gold quality
gastrocnemius	UBERON:0001388	89.39	gold quality
intestine	UBERON:0000160	89.29	gold quality
muscle of leg	UBERON:0001383	88.97	gold quality
body of stomach	UBERON:0001161	88.75	gold quality
omental fat pad	UBERON:0010414	88.44	gold quality
right uterine tube	UBERON:0001302	88.43	gold quality
thoracic mammary gland	UBERON:0005200	88.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.77
E-GEOD-36552	no	58.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting ACY1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-212-5P	96.83	67.43	950

Literature-anchored findings (GeneRIF, showing 14)

• by complementing different active site mutants of human aminoacylase-1, study shows that catalysis occurs at the dimer interface (PMID:12933810)
• first report of a patient with aminoacylase I deficiency (PMID:16274666)
• Genetic deficiency of ACY1 leads to functional ACY1 deficiency and excretion of N-acetylated amino acids. (PMID:16465618)
• Because hK1 amidase activity is significantly lower in urine of systolic HF patients, it can be supposed that activity of renal kallikrein-kinin system may be suppressed in this systolic heart failure. (PMID:17045186)
• T347S variant of human Acy1 exhibited markedly increased catalytic efficiency against N-benzoylamino acids (PMID:18341290)
• These data suggest that aminoacylase expression is dysregulated in neuroblastoma. (PMID:21128244)
• aminoacylase 1 proteins with the mutations p.Arg378Trp, p.Arg378Gln and p.Arg393His were also detected in Western blot analysis (PMID:21414403)
• We concluded that ACY1 expression in colorectal cancer varies with stage and appears to play a role in cell proliferation and apoptosis (PMID:23317546)
• Report serum aminoacylase-1 as a novel biomarker with potential prognostic utility for long-term outcome in renal transplant recipients with delayed graft function. (PMID:23739232)
• Biochemical analysis showed absence of ACY1 enzyme activity in the patient’s fibroblasts. (PMID:24117009)
• ACY1 acts as a tumor suppressor in hepatocellular carcinoma. (PMID:24846301)
• with the elevated level in the disease progression of Chronic hepatitis B (CHB), ACY1 autoantibody may be a valuable serum biomarker for discriminating HBVrelated liver cirrhosis from CHB. (PMID:27633755)
• Aminoacylase 1 (ACY-1) Mediates the Proliferation and Migration of Neuroblastoma Cells in Humans Through the ERK/Transforming Growth Factor beta (TGF-beta) Signaling Pathways. (PMID:33619241)
• LncRNA MAGI2-AS3 inhibits tumor progression and angiogenesis by regulating ACY1 via interacting with transcription factor HEY1 in clear cell renal cell carcinoma. (PMID:34002044)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	acy1	ENSDARG00000038475
danio_rerio	ACY1	ENSDARG00000111129
mus_musculus	Acy1	ENSMUSG00000023262
rattus_norvegicus	Acy1	ENSRNOG00000011189
drosophila_melanogaster	CG6465	FBGN0037818
drosophila_melanogaster	CG6726	FBGN0039049
drosophila_melanogaster	CG17110	FBGN0039050
drosophila_melanogaster	CG17109	FBGN0039051
drosophila_melanogaster	CG6733	FBGN0039052
drosophila_melanogaster	CG6738	FBGN0039053
caenorhabditis_elegans		WBGENE00007507
caenorhabditis_elegans		WBGENE00007508
caenorhabditis_elegans		WBGENE00007509
caenorhabditis_elegans		WBGENE00015509

Paralogs (3): CNDP2 (ENSG00000133313), CNDP1 (ENSG00000150656), PM20D1 (ENSG00000162877)

Protein

Protein identifiers

Aminoacylase-1 — Q03154 (reviewed: Q03154)

Alternative names: N-acyl-L-amino-acid amidohydrolase

All UniProt accessions (11): A0A1B0GTG3, A0A1B0GU36, A0A1B0GU86, A0A1B0GUZ4, A0A1B0GVF7, A0A1B0GVG0, A0A1B0GVZ3, C9JYZ0, Q03154, F8WC59, V9HWA0

UniProt curated annotations — full annotation on UniProt →

Function. Aminoacylase involved in the hydrolysis of N-acetylated and N-formylated amino acids. May act sequentially with APEH in the degradation of N-acylated peptides: APEH first cleaves N-acylaminoacids from N-acylated peptides, then ACY1 further hydrolyzes the N-acylaminoacid into free aminoacid and a carboxylate.

Subunit / interactions. Homodimer. Interacts with SPHK1.

Subcellular location. Cytoplasm.

Tissue specificity. Expression is highest in kidney, strong in brain and weaker in placenta and spleen.

Disease relevance. Aminoacylase-1 deficiency (ACY1D) [MIM:609924] An enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Similarity. Belongs to the peptidase M20A family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q03154-1	1	yes
Q03154-2	2
Q03154-3	3
Q03154-4	4

RefSeq proteins (5): NP_000657, NP_001185824, NP_001185825, NP_001185826, NP_001185827 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001261	ArgE/DapE_CS	Conserved_site
IPR002933	Peptidase_M20	Family
IPR010159	N-acyl_aa_amidohydrolase	Family
IPR011650	Peptidase_M20_dimer	Domain
IPR036264	Bact_exopeptidase_dim_dom	Homologous_superfamily
IPR052083	Aminoacylase-1_M20A	Family

Pfam: PF01546, PF07687

Enzyme classification (BRENDA):

• EC 3.5.1.14 — N-acyl-aliphatic-L-amino acid amidohydrolase (BRENDA: 36 organisms, 411 substrates, 135 inhibitors, 209 Km, 119 kcat entries)

Substrate kinetics (BRENDA)

102 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-ACETYL-L-METHIONINE	0.013–24.6	26
N-ALPHA-ACETYL-L-METHIONINE	0.84–7.7	13
N-ACETYL-L-PHENYLALANINE	1.6–10.3	8
NALPHA-ACETYLMETHIONINE	0.39–67.4	7
N-ACETYL-L-GLUTAMATE	63–102	5
N-ISOPENTANOYL-L-METHIONINE	0.54–7.29	5
N-ACETYL-L-GLUTAMINE	7–62.3	4
N-ACETYL-L-MET	0.2–11.3	4
N-BENZOYL-L-METHIONINE	0.38–1.63	4
N-HEXANOYL-L-METHIONINE	0.01–5.22	4
2-ACETYLAMINO-3-((1S,2S)-2-HYDROXY-2,2-DIMETHYL-	0.1–0.2	3
2-ACETYLAMINO-3-((1S,2S)-2-HYDROXYCYCLOHEXYLSULF	0.3–0.5	3
2-ACETYLAMINO-3-[(S)-1-((R)-HYDROXYPHENYL-METHYL	0.2–0.4	3
N-ACETYL-L-CYS	0.4–0.5	3
N-ACETYL-L-CYSTEINE	1.4–4.4	3

Catalyzed reactions (Rhea), 4 shown:

• an N-acyl-L-amino acid + H2O = an L-alpha-amino acid + a carboxylate (RHEA:15565)
• N(alpha)-formyl-L-methionine + H2O = formate + L-methionine (RHEA:17781)
• N-acetyl-L-glutamine + H2O = L-glutamine + acetate (RHEA:67368)
• N-acetyl-L-methionine + H2O = L-methionine + acetate (RHEA:67440)

UniProt features (54 total): helix 12, strand 10, sequence variant 9, mutagenesis site 8, binding site 6, splice variant 3, turn 3, active site 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1Q7L	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03154-F1	96.55	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 82; 147 (proton acceptor)

Ligand- & substrate-binding residues (6): 80; 113; 113; 148; 175; 373

Mutagenesis-validated functional residues (8):

Position	Phenotype
80	almost abolishes enzyme activity.
113	almost abolishes enzyme activity.
147	almost abolishes enzyme activity.
147	decreased protein stability. loss of enzyme activity.
148	almost abolishes enzyme activity.
175	almost abolishes enzyme activity.
206	almost abolishes enzyme activity.
373	almost abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5423646	Aflatoxin activation and detoxification
R-HSA-5579007	Defective ACY1 causes encephalopathy
R-HSA-9753281	Paracetamol ADME
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-211859	Biological oxidations
R-HSA-5579029	Metabolic disorders of biological oxidation enzymes
R-HSA-5668914	Diseases of metabolism
R-HSA-9748784	Drug ADME

MSigDB gene sets: 215 (showing top): MODULE_172, RNGTGGGC_UNKNOWN, REACTOME_BIOLOGICAL_OXIDATIONS, LUCAS_HNF4A_TARGETS_UP, BROWNE_HCMV_INFECTION_48HR_DN, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, MYCMAX_01, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, LXR_Q3, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, MODULE_440, BARIS_THYROID_CANCER_DN, BOYLAN_MULTIPLE_MYELOMA_C_D_UP, LIU_SOX4_TARGETS_DN

GO Biological Process (1): amino acid metabolic process (GO:0006520)

GO Molecular Function (5): aminoacylase activity (GO:0004046), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Biological oxidations	1
Metabolic disorders of biological oxidation enzymes	1
Drug ADME	1
Metabolism	1
Diseases of metabolism	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
primary metabolic process	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
protein binding	1
cation binding	1
binding	1
catalytic activity	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1839 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACY1	ASPA	P45381	981
ACY1	APEH	P13798	880
ACY1	SPHK1	Q9NYA1	819
ACY1	ACY3	Q96HD9	792
ACY1	GLB1	P16278	777
ACY1	ALAS1	P13196	573
ACY1	ALDH18A1	P54886	568
ACY1	LTF	P02788	554
ACY1	ASS1	P00966	549
ACY1	CDC42EP2	O14613	513
ACY1	AHSG	P02765	501
ACY1	GOSR1	O95249	491
ACY1	BCHE	P06276	465
ACY1	NAGS	Q8N159	457
ACY1	SERPING1	P05155	440

IntAct

81 interactions, top by confidence:

A	B	Type	Score
PPME1	PPP2R1A	psi-mi:“MI:0914”(association)	0.950
PPME1	PPP2CA	psi-mi:“MI:0914”(association)	0.880
ACY1	ACY1	psi-mi:“MI:0915”(physical association)	0.850
NUDT1	ACY1	psi-mi:“MI:0914”(association)	0.670
NUDT1	ACY1	psi-mi:“MI:0915”(physical association)	0.670
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
	DDX3X	psi-mi:“MI:0914”(association)	0.630
BCAS2	ACY1	psi-mi:“MI:0915”(physical association)	0.560
ACY1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
ACY1	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
PRR35	ACY1	psi-mi:“MI:0915”(physical association)	0.560
TLX3	ACY1	psi-mi:“MI:0915”(physical association)	0.560
ACY1	WWOX	psi-mi:“MI:0915”(physical association)	0.560
NUDT1	ACY1	psi-mi:“MI:0915”(physical association)	0.550
TTC1	ACY1	psi-mi:“MI:0915”(physical association)	0.550
ACY1	TTC1	psi-mi:“MI:0915”(physical association)	0.550
PECR	LCN1	psi-mi:“MI:0914”(association)	0.530
TERF1	ACY1	psi-mi:“MI:0915”(physical association)	0.510
PHOSPHO1	ACY1	psi-mi:“MI:0914”(association)	0.500
PHOSPHO1	ACY1	psi-mi:“MI:0915”(physical association)	0.500
ACY1	TRIM33	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (78): NUDT1 (Two-hybrid), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), ACY1 (Affinity Capture-MS), TTC1 (Two-hybrid), ACY1 (Two-hybrid), ACY1 (Co-fractionation), ACY1 (Co-fractionation), ACY1 (Co-fractionation), ACY1 (Co-fractionation)

ESM2 similar proteins: A3KG59, A4IFH5, B9N1F9, D3ZVR9, O04059, O35331, O35621, O46560, P11172, P24298, P37111, Q03154, Q04609, Q15124, Q17QK3, Q2R483, Q501L1, Q5E9T8, Q5I0K3, Q5NAY4, Q5R514, Q5R5C9, Q5RDE7, Q5RDN7, Q5RFB0, Q5RFI8, Q6AY30, Q6AYS7, Q6K2E8, Q6PTT0, Q6Q0N1, Q6ZV70, Q7TSV4, Q7X7L3, Q8BZF8, Q8CG45, Q8CG76, Q8IYS1, Q8K183, Q8N0X4

Diamond homologs: A1RJ78, A1TQ19, A1U3R0, A1VN92, A1W7M0, A3D547, A3QE30, A4JF88, A4SPS7, A4Y7B1, A5CXE9, A5UB44, A5UFQ7, A5WD56, A6VMI0, A6WNV3, A7HPQ6, A8GHK9, A8H424, A9AHS8, A9CKC4, A9KC82, A9L3M8, A9NCE9, B0RW53, B0TVI4, B1JUG2, B1KDS3, B1Y6E7, B2FIC0, B2I6B4, B2IDW3, B2UAZ1, B4RSS7, B4RZS0, B6EJS8, B6J120, B6J929, B8EA23, B8GPR9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

16 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	9
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2426146	NC_000003.11:g.(?52018081)(52188388_?)del	Pathogenic
4849441	NM_000666.3(ACY1):c.526+1G>A	Likely pathogenic

SpliceAI

1813 predictions. Top by Δscore:

Variant	Effect	Δscore
3:51983544:G:T	donor_gain	1.0000
3:51983583:GA:G	donor_gain	1.0000
3:51984045:A:AG	acceptor_gain	1.0000
3:51984046:G:GG	acceptor_gain	1.0000
3:51984159:G:GG	donor_gain	1.0000
3:51984172:G:GA	donor_gain	1.0000
3:51984191:GGGCC:G	donor_gain	1.0000
3:51984201:G:T	donor_gain	1.0000
3:51985357:CCAG:C	acceptor_loss	1.0000
3:51985358:CAG:C	acceptor_loss	1.0000
3:51985359:AGGT:A	acceptor_gain	1.0000
3:51985360:GGT:G	acceptor_gain	1.0000
3:51985360:GGTG:G	acceptor_gain	1.0000
3:51985445:G:GT	donor_gain	1.0000
3:51985462:CAAG:C	donor_loss	1.0000
3:51985463:AAG:A	donor_loss	1.0000
3:51985463:AAGG:A	donor_loss	1.0000
3:51985464:AGG:A	donor_loss	1.0000
3:51985466:GT:G	donor_loss	1.0000
3:51985467:T:G	donor_loss	1.0000
3:51985943:TCCA:T	donor_gain	1.0000
3:51985947:G:GG	donor_gain	1.0000
3:51986409:TTACA:T	acceptor_loss	1.0000
3:51986410:TACAG:T	acceptor_loss	1.0000
3:51986411:ACAGA:A	acceptor_loss	1.0000
3:51986412:CA:C	acceptor_loss	1.0000
3:51986413:A:AG	acceptor_gain	1.0000
3:51986414:G:A	acceptor_loss	1.0000
3:51986414:G:GA	acceptor_gain	1.0000
3:51986414:G:T	acceptor_loss	1.0000

AlphaMissense

2683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:51985926:C:A	D113E	0.996
3:51985926:C:G	D113E	0.996
3:51985925:A:C	D113A	0.995
3:51985925:A:T	D113V	0.995
3:51985924:G:C	D113H	0.994
3:51986418:A:T	E147V	0.994
3:51985439:C:G	H80D	0.993
3:51986265:G:C	A124P	0.993
3:51985913:G:T	R109M	0.992
3:51987428:G:C	R276P	0.992
3:51988806:G:C	D348H	0.992
3:51988933:T:C	F362S	0.992
3:51988965:C:G	H373D	0.992
3:51988978:A:T	E377V	0.992
3:51985441:C:A	H80Q	0.991
3:51985441:C:G	H80Q	0.991
3:51985923:G:C	Q112H	0.991
3:51985923:G:T	Q112H	0.991
3:51986419:G:C	E147D	0.991
3:51986419:G:T	E147D	0.991
3:51986635:T:A	V186D	0.991
3:51988967:C:A	H373Q	0.991
3:51988967:C:G	H373Q	0.991
3:51988807:A:T	D348V	0.990
3:51988965:C:A	H373N	0.990
3:51985925:A:G	D113G	0.989
3:51986468:T:C	F164L	0.989
3:51986470:C:A	F164L	0.989
3:51986470:C:G	F164L	0.989
3:51986504:G:C	G176R	0.989

dbSNP variants (sampled 300 via entrez): RS1000030880 (3:51984386 G>T), RS1000158492 (3:51988315 G>T), RS1000229052 (3:51987940 C>T), RS1001358393 (3:51988095 G>T), RS1001898839 (3:51989324 C>T), RS1001925490 (3:51981984 G>A), RS1002691352 (3:51982972 CTT>C), RS1004030700 (3:51983348 C>G,T), RS1004137788 (3:51983738 G>T), RS1004530477 (3:51983981 C>A,G,T), RS1004697756 (3:51987143 A>C,G), RS1005796039 (3:51985720 G>A), RS1005966131 (3:51988642 C>A), RS1006755231 (3:51984492 G>A,C), RS1007222384 (3:51984212 T>C)

Disease associations

OMIM: gene MIM:104620 | disease phenotypes: MIM:609924

GenCC curated gene-disease

Disease	Classification	Inheritance
aminoacylase 1 deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
aminoacylase 1 deficiency	Definitive	AR

Mondo (1): aminoacylase 1 deficiency (MONDO:0012368)

Orphanet (1): Aminoacylase 1 deficiency (Orphanet:137754)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000316	Hypertelorism
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000752	Hyperactivity
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001623	Breech presentation
HP:0001662	Bradycardia
HP:0002013	Vomiting
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002104	Apnea
HP:0002120	Cerebral cortical atrophy
HP:0002188	Delayed CNS myelination
HP:0003324	Generalized muscle weakness
HP:0003396	Syringomyelia
HP:0003623	Neonatal onset
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis
HP:0006846	Acute encephalopathy
HP:0007370	Aplasia/Hypoplasia of the corpus callosum
HP:0011968	Feeding difficulties

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST012353_28	Serum metabolite concentrations in chronic kidney disease	5.000000e-13
GCST012353_29	Serum metabolite concentrations in chronic kidney disease	6.000000e-13
GCST012353_30	Serum metabolite concentrations in chronic kidney disease	2.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538246	Aminoacylase 1 deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
bisphenol A	affects expression, increases expression	2
Phenobarbital	affects expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
bisphenol F	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
periodate-oxidized adenosine	affects expression	1
K 7174	decreases expression	1
candoxin	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding	1
Dust	decreases expression	1
Fluorouracil	affects reaction, decreases expression	1
Hydrogen Peroxide	increases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Selenium	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2HW	Abcam Raji ACY1 KO	Cancer cell line	Male
CVCL_DX69	HAP1 ACY1 (-)	Cancer cell line	Male
CVCL_UQ07	Abcam Jurkat ACY1 KO	Cancer cell line	Male
CVCL_WQ91	Abcam K-562 ACY1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.