ACY3

Summary

ACY3 (aminoacylase 3, HGNC:24104) is a protein-coding gene on chromosome 11q13.2, encoding N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming) (Q96HD9). Plays an important role in deacetylating mercapturic acids in kidney proximal tubules.

Predicted to enable aminoacylase activity. Located in extracellular exosome.

Source: NCBI Gene 91703 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 89 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_080658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24104
Approved symbol	ACY3
Name	aminoacylase 3
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	HCBP1, MGC9740, ACY-3, ASPA2
Ensembl gene	ENSG00000132744
Ensembl biotype	protein_coding
OMIM	614413
Entrez	91703

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000255082, ENST00000529256, ENST00000897123, ENST00000897124, ENST00000897125, ENST00000897126, ENST00000897127, ENST00000897128, ENST00000897129, ENST00000897130, ENST00000897131

RefSeq mRNA: 1 — MANE Select: NM_080658 NM_080658

CCDS: CCDS8175

Canonical transcript exons

ENST00000255082 — 8 exons

Exon	Start	End
ENSE00000904445	67645287	67645380
ENSE00000904447	67646808	67647063
ENSE00001064201	67650583	67650730
ENSE00001185303	67642555	67642939
ENSE00001185309	67644760	67644869
ENSE00001185316	67645045	67645152
ENSE00001185335	67647516	67647589
ENSE00003593344	67645692	67645887

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 94.12.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9147 / max 167.5784, expressed in 204 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120968	0.5206	82
120963	0.1981	72
120966	0.0773	34
120965	0.0417	10
120964	0.0299	14
120969	0.0271	6
120967	0.0200	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	94.12	gold quality
kidney epithelium	UBERON:0004819	91.89	gold quality
right lobe of liver	UBERON:0001114	90.19	gold quality
duodenum	UBERON:0002114	89.79	gold quality
adult mammalian kidney	UBERON:0000082	89.43	gold quality
jejunal mucosa	UBERON:0000399	86.82	gold quality
body of pancreas	UBERON:0001150	84.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.33	gold quality
small intestine	UBERON:0002108	82.98	gold quality
mucosa of transverse colon	UBERON:0004991	82.93	gold quality
kidney	UBERON:0002113	82.60	gold quality
liver	UBERON:0002107	82.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.07	gold quality
jejunum	UBERON:0002115	78.95	gold quality
renal medulla	UBERON:0000362	78.60	gold quality
cortex of kidney	UBERON:0001225	78.02	gold quality
cerebellar vermis	UBERON:0004720	77.56	gold quality
upper arm skin	UBERON:0004263	76.91	gold quality
metanephros cortex	UBERON:0010533	76.35	gold quality
left ventricle myocardium	UBERON:0006566	74.78	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.54	gold quality
vena cava	UBERON:0004087	74.42	gold quality
tibialis anterior	UBERON:0001385	74.00	silver quality
pancreas	UBERON:0001264	73.47	gold quality
cardia of stomach	UBERON:0001162	72.77	gold quality
prefrontal cortex	UBERON:0000451	72.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.46	gold quality
inferior vagus X ganglion	UBERON:0005363	72.43	silver quality
subthalamic nucleus	UBERON:0001906	72.35	silver quality
spinal cord	UBERON:0002240	72.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	198.86
E-ANND-3	yes	4.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting ACY3, 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-6825-5P	99.96	69.81	3431
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6865-5P	96.05	65.58	675
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6765-5P	94.51	62.65	164
HSA-MIR-6089	89.72	61.35	324

Literature-anchored findings (GeneRIF, showing 1)

• Suggest that ACY3 is an HCV core binding protein, which may play a role in the development of HCV-associated diseases. (PMID:19486448)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acy3.2	ENSDARG00000005525
danio_rerio	acy3.1	ENSDARG00000093003
mus_musculus	Acy3	ENSMUSG00000024866
rattus_norvegicus	Acy3	ENSRNOG00000017901

Paralogs (1): ASPA (ENSG00000108381)

Protein

Protein identifiers

N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming) — Q96HD9 (reviewed: Q96HD9)

Alternative names: Acylase III, Aminoacylase-3, Aspartoacylase-2, Hepatitis C virus core-binding protein 1

All UniProt accessions (2): Q96HD9, E9PRA7

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in deacetylating mercapturic acids in kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids.

Subunit / interactions. Exists as a mixture of homodimers and homotetramer, both catalytically active. (Microbial infection) Interacts with hepatitis C virus/HCV core protein.

Subcellular location. Apical cell membrane. Cytoplasm.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the AspA/AstE family. Aspartoacylase subfamily.

RefSeq proteins (1): NP_542389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007036	Aste_AspA_hybrid_dom	Domain
IPR016708	Aspartoacylase	Family
IPR050178	AspA/AstE_fam	Family
IPR055438	AstE_AspA_cat	Domain

Pfam: PF04952, PF24827

Enzyme classification (BRENDA):

• EC 3.5.1.114 — N-acyl-aromatic-L-amino acid amidohydrolase (BRENDA: 3 organisms, 29 substrates, 13 inhibitors, 73 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
N-ACETYL-L-TYROSINE	0.18–5.2	29
N-ACETYL-1,2-DICHLOROVINYL-L-CYSTEINE	1.11–17.73	16
N-ACETYL-S-(1,2-DICHLOROVINYL)-L-CYSTEINE	0.56–1.3	3
4-HYDROXY-2-NONENAL MERCAPTURATE	0.2–0.53	2
ACROLEIN MERCAPTURATE	0.71–0.82	2
N-ACETYL-L-HISTIDINE	1.8	1
N-ACETYL-L-LYSINE	1.3	1
N-ACETYL-L-PHENYLALANINE	1.6	1
N-ACETYL-L-TRYPTOPHAN	1.2	1
N-ACETYL-S-(1,1,2,2-TETRAFLUOROETHYL)-L-CYSTEINE	0.25	1
N-ACETYL-S-(1,2,2-TRICHLOROVINYL)-L-CYSTEINE	1.2	1
N-ACETYL-S-(1,2,3,4,4-PENTACHLOROBUTADIENYL)-L-C	1	1
N-ACETYL-S-(2,2-DICHLORO-1,1-DIFLUOROETHYL)-L-CY	5.3	1
N-ACETYL-S-(2,2-DICHLOROVINYL)-L-CYSTEINE	0.4	1
N-ACETYL-S-(2,2-DIFLUORO-1,1-DICHLOROETHYL)-L-CY	0.3	1

Catalyzed reactions (Rhea), 2 shown:

• an N-acetyl-L-cysteine-S-conjugate + H2O = an S-substituted L-cysteine + acetate (RHEA:36855)
• an N-acyl-aromatic L-alpha-amino acid + H2O = an aromatic L-alpha-amino acid + a carboxylate (RHEA:54184)

UniProt features (12 total): binding site 7, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HD9-F1	95.61	0.93

Functional residue map

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

Ligand- & substrate-binding residues (7): 21; 24; 63; 70–71; 116; 178; 288

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5423646	Aflatoxin activation and detoxification
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations

MSigDB gene sets: 81 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, chr11q13, CATRRAGC_UNKNOWN, KEGG_HISTIDINE_METABOLISM, SANSOM_APC_TARGETS_DN, GOCC_APICAL_PLASMA_MEMBRANE, RYTTCCTG_ETS2_B, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, TAL1BETAE47_01, GOCC_APICAL_PART_OF_CELL, GOCC_PLASMA_MEMBRANE_REGION, KEGG_ALANINE_ASPARTATE_AND_GLUTAMATE_METABOLISM, STAT5A_01, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, SMAD4_Q6

GO Biological Process (0):

GO Molecular Function (7): aminoacylase activity (GO:0004046), hydrolase activity, acting on ester bonds (GO:0016788), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811)

GO Cellular Component (6): cytosol (GO:0005829), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
hydrolase activity	1
protein binding	1
cation binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cytoplasm	1
apical part of cell	1
plasma membrane region	1
extracellular vesicle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACY3	ACY1	Q03154	792
ACY3	ASPNAT	Q8N9F0	457
ACY3	DHRS9	Q9BPW9	449
ACY3	ASPA	P45381	417
ACY3	ZNF705B	P0CI00	400
ACY3	SUSD3	Q96L08	376
ACY3	RASAL3	Q86YV0	355
ACY3	SASH3	O75995	348
ACY3	NOXRED1	Q6NXP6	341
ACY3	NT5DC4	Q86YG4	322
ACY3	NAT8	Q9UHE5	321
ACY3	IGSF6	O95976	319
ACY3	AKAP6	Q13023	308
ACY3	ZNF486	Q96H40	290
ACY3	SPIN2A	Q99865	290

IntAct

99 interactions, top by confidence:

A	B	Type	Score
GORASP2	ACY3	psi-mi:“MI:0915”(physical association)	0.870
ACY3	GORASP2	psi-mi:“MI:0915”(physical association)	0.870
PMM2	ACY3	psi-mi:“MI:0915”(physical association)	0.810
ASPA	ACY3	psi-mi:“MI:0915”(physical association)	0.810
ACY3	ASPA	psi-mi:“MI:0915”(physical association)	0.810
ACY3	PMM2	psi-mi:“MI:0915”(physical association)	0.810
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
ACY3	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.670
PLEKHF2	ACY3	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (34): ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid), ACY3 (Two-hybrid)

ESM2 similar proteins: A4FV58, A5GFZ6, A6H791, A6H7F2, D3ZAA9, D4A1R8, D4A7C0, E7F3I6, H1UBN0, O88618, P49004, Q02053, Q08DB4, Q4IQT8, Q4PF70, Q4QR99, Q4R4J2, Q4R579, Q4WT40, Q56XY2, Q58DD9, Q5BJ53, Q5E9M9, Q5R762, Q5RF36, Q5U300, Q5ZKI2, Q66JK4, Q66KF6, Q6NS21, Q6PUR6, Q7TMW6, Q7TSA0, Q7YRA3, Q86U10, Q8C166, Q8CHW4, Q8IXI1, Q8JZN7, Q8VEJ1

Diamond homologs: A0JMS7, A2BP19, A2BUK0, A3PAU1, A8G2N0, A8KB34, B0C2K7, B1PK17, P45381, P46446, P59829, P59830, P72208, P73211, Q10VR3, Q28C61, Q31CV9, Q3AM91, Q3AV13, Q3MC79, Q46HE9, Q5BJ91, Q5M876, Q5R9E0, Q60HH2, Q6DHI0, Q6DHQ3, Q7V5L6, Q8R3P0, Q8YQC1, Q91XE4, Q96HD9, Q9R1T5, A1ABS5, A1JS32, A2C055, A3M9D1, A4TJU3, A4XWE4, A7FIL2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	69
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
58892	GRCh38/hg38 11q13.2(chr11:66885910-67698250)x1	Pathogenic
58893	GRCh38/hg38 11q13.2(chr11:67446153-68679073)x1	Pathogenic
146304	GRCh38/hg38 11q13.2-13.3(chr11:67217264-69448598)x1	Likely pathogenic

SpliceAI

1394 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67645042:CA:C	donor_loss	1.0000
11:67645043:A:AC	donor_gain	1.0000
11:67645043:AC:A	donor_gain	1.0000
11:67645044:C:CC	donor_gain	1.0000
11:67645044:C:CT	donor_loss	1.0000
11:67645044:CC:C	donor_gain	1.0000
11:67645148:CAGAC:C	acceptor_gain	1.0000
11:67645150:GAC:G	acceptor_gain	1.0000
11:67645151:AC:A	acceptor_gain	1.0000
11:67645151:ACC:A	acceptor_loss	1.0000
11:67645152:CC:C	acceptor_gain	1.0000
11:67645153:C:CA	acceptor_loss	1.0000
11:67645153:C:CC	acceptor_gain	1.0000
11:67645154:T:A	acceptor_loss	1.0000
11:67645263:A:AC	donor_gain	1.0000
11:67645264:C:CC	donor_gain	1.0000
11:67645266:T:TA	donor_gain	1.0000
11:67645289:AGT:A	donor_gain	1.0000
11:67645656:C:A	donor_gain	1.0000
11:67645726:T:TA	donor_gain	1.0000
11:67645739:T:TA	donor_gain	1.0000
11:67645883:TGGAA:T	acceptor_gain	1.0000
11:67645888:C:CC	acceptor_gain	1.0000
11:67646805:CACT:C	donor_loss	1.0000
11:67646806:A:AC	donor_gain	1.0000
11:67646806:AC:A	donor_loss	1.0000
11:67646807:C:CC	donor_gain	1.0000
11:67646807:CT:C	donor_gain	1.0000
11:67646807:CTTG:C	donor_gain	1.0000
11:67642940:CTG:C	acceptor_loss	0.9900

AlphaMissense

2060 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67646825:G:C	F73L	0.986
11:67646825:G:T	F73L	0.986
11:67646827:A:G	F73L	0.986
11:67642830:T:A	E285V	0.978
11:67642838:G:C	F282L	0.977
11:67642838:G:T	F282L	0.977
11:67642840:A:G	F282L	0.977
11:67646973:T:A	E24V	0.977
11:67642803:G:T	A294D	0.970
11:67642833:T:A	N284I	0.970
11:67642832:G:C	N284K	0.968
11:67642832:G:T	N284K	0.968
11:67646832:C:G	R71P	0.967
11:67642899:A:G	F262S	0.965
11:67645773:G:C	N117K	0.962
11:67645773:G:T	N117K	0.962
11:67645778:G:C	H116D	0.962
11:67642829:C:A	E285D	0.960
11:67642829:C:G	E285D	0.960
11:67646979:C:A	G22V	0.958
11:67642898:G:C	F262L	0.953
11:67642898:G:T	F262L	0.953
11:67642900:A:G	F262L	0.953
11:67642928:G:C	F252L	0.948
11:67642928:G:T	F252L	0.948
11:67642930:A:G	F252L	0.948
11:67646975:G:C	N23K	0.948
11:67646975:G:T	N23K	0.948
11:67646882:G:C	N54K	0.947
11:67646882:G:T	N54K	0.947

dbSNP variants (sampled 300 via entrez): RS1000119125 (11:67649982 C>T), RS1000378689 (11:67651313 C>A,T), RS1000927932 (11:67643270 T>G), RS1001117418 (11:67649970 C>G), RS1001527936 (11:67647177 G>A,C,T), RS1001979648 (11:67650776 T>C), RS1002035255 (11:67643607 G>A), RS1002376142 (11:67645926 C>G), RS1002501476 (11:67645888 C>A,T), RS1002597812 (11:67648174 C>A), RS1002610847 (11:67650178 A>G,T), RS1002719363 (11:67646057 C>G,T), RS1002805788 (11:67648914 C>T), RS1002934346 (11:67648433 A>T), RS1003727622 (11:67644919 G>C,T)

Disease associations

OMIM: gene MIM:614413 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002388_8	Serum metabolite levels	9.000000e-16
GCST009733_179	Urinary metabolite levels in chronic kidney disease	1.000000e-11
GCST009733_183	Urinary metabolite levels in chronic kidney disease	8.000000e-13
GCST009735_12	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	9.000000e-12
GCST012020_187	Serum metabolite levels	3.000000e-45
GCST012020_188	Serum metabolite levels	5.000000e-13
GCST012020_435	Serum metabolite levels	2.000000e-24
GCST012020_522	Serum metabolite levels	3.000000e-24
GCST012021_112	Serum metabolite levels	3.000000e-45
GCST012021_113	Serum metabolite levels	5.000000e-13
GCST012021_63	Serum metabolite levels	3.000000e-24
GCST012353_4	Serum metabolite concentrations in chronic kidney disease	1.000000e-22
GCST012353_40	Serum metabolite concentrations in chronic kidney disease	2.000000e-12
GCST012353_41	Serum metabolite concentrations in chronic kidney disease	4.000000e-17
GCST012353_42	Serum metabolite concentrations in chronic kidney disease	8.000000e-16
GCST90020029_348	Waist circumference adjusted for body mass index	2.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2514036	Efficacy	3	bisoprolol	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2514036	ACY3	3	0.00	1	bisoprolol

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation, affects methylation	2
sotorasib	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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