APEH

Summary

APEH (acylaminoacyl-peptide hydrolase, HGNC:586) is a protein-coding gene on chromosome 3p21.31, encoding Acylamino-acid-releasing enzyme (P13798). Aminopeptidase involved in the degradation of N(alpha)-acylated peptides.

This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma.

Source: NCBI Gene 327 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 110 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001640

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:586
Approved symbol	APEH
Name	acylaminoacyl-peptide hydrolase
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164062
Ensembl biotype	protein_coding
OMIM	102645
Entrez	327

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 29 protein_coding, 7 retained_intron, 4 nonsense_mediated_decay

ENST00000296456, ENST00000438011, ENST00000442186, ENST00000446089, ENST00000447436, ENST00000447541, ENST00000449966, ENST00000457042, ENST00000462439, ENST00000463616, ENST00000463995, ENST00000469362, ENST00000480772, ENST00000482301, ENST00000483715, ENST00000491799, ENST00000863157, ENST00000863158, ENST00000863159, ENST00000863160, ENST00000863161, ENST00000863162, ENST00000863163, ENST00000863164, ENST00000863165, ENST00000863166, ENST00000863167, ENST00000863168, ENST00000863169, ENST00000863170, ENST00000863171, ENST00000863172, ENST00000925194, ENST00000925195, ENST00000925196, ENST00000959864, ENST00000959865, ENST00000959866, ENST00000959867, ENST00000959868

RefSeq mRNA: 1 — MANE Select: NM_001640 NM_001640

CCDS: CCDS2801

Canonical transcript exons

ENST00000296456 — 22 exons

Exon	Start	End
ENSE00001235167	49680541	49680629
ENSE00001235173	49679593	49679644
ENSE00001342693	49674351	49674413
ENSE00001716756	49683040	49683146
ENSE00001882525	49683237	49683971
ENSE00003459328	49676378	49676515
ENSE00003462689	49676777	49676817
ENSE00003501589	49681887	49681967
ENSE00003515732	49681101	49681239
ENSE00003537332	49682843	49682945
ENSE00003560933	49675183	49675309
ENSE00003579456	49676609	49676700
ENSE00003598996	49678852	49678949
ENSE00003629333	49676903	49677024
ENSE00003637133	49682348	49682436
ENSE00003637146	49682546	49682736
ENSE00003655897	49677573	49677633
ENSE00003667243	49674489	49674621
ENSE00003674369	49675694	49675787
ENSE00003679869	49675891	49675966
ENSE00003681933	49676056	49676219
ENSE00003683900	49681722	49681805

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.0344 / max 162.4997, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36653	34.4573	1824
36652	5.3292	1735
36650	0.1841	76
36651	0.0637	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.93	gold quality
metanephros cortex	UBERON:0010533	97.54	gold quality
adenohypophysis	UBERON:0002196	97.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.09	gold quality
right lobe of thyroid gland	UBERON:0001119	97.04	gold quality
left lobe of thyroid gland	UBERON:0001120	96.97	gold quality
right adrenal gland	UBERON:0001233	96.87	gold quality
right adrenal gland cortex	UBERON:0035827	96.74	gold quality
apex of heart	UBERON:0002098	96.72	gold quality
left adrenal gland	UBERON:0001234	96.59	gold quality
left adrenal gland cortex	UBERON:0035825	96.57	gold quality
granulocyte	CL:0000094	96.52	gold quality
pituitary gland	UBERON:0000007	96.40	gold quality
gastrocnemius	UBERON:0001388	96.38	gold quality
ventricular zone	UBERON:0003053	96.31	gold quality
body of stomach	UBERON:0001161	96.24	gold quality
rectum	UBERON:0001052	96.19	gold quality
thyroid gland	UBERON:0002046	96.12	gold quality
right lobe of liver	UBERON:0001114	96.07	gold quality
transverse colon	UBERON:0001157	96.00	gold quality
ganglionic eminence	UBERON:0004023	95.99	gold quality
body of pancreas	UBERON:0001150	95.91	gold quality
adrenal gland	UBERON:0002369	95.78	gold quality
muscle of leg	UBERON:0001383	95.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.56	gold quality
adrenal cortex	UBERON:0001235	95.54	gold quality
islet of Langerhans	UBERON:0000006	95.46	gold quality
prefrontal cortex	UBERON:0000451	95.30	gold quality
esophagus mucosa	UBERON:0002469	95.26	gold quality
minor salivary gland	UBERON:0001830	95.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JDP2

miRNA regulators (miRDB)

9 targeting APEH, 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-32-3P	99.36	68.20	2517
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-6847-3P	96.50	67.30	582
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-4268	94.45	64.09	819

Literature-anchored findings (GeneRIF, showing 6)

• Studies indicate that the cylindromatosis/turban tumor syndrome gene (CYLD) ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4). (PMID:21931648)
• APEH polymorphism has significant influence on valproic acid pharmacokinetics in Chinese population (PMID:27406852)
• Although APEH is primarily localized in the cytoplasm, a sub-fraction of this enzyme is sequestered at sites of nuclear damage following UVA irradiation or following oxidative stress. APEH interacts with the amino-terminal domain of XRCC1, and APEH facilitates both single-strand break repair and cell survival following exposure to H2O2. Thus, APEH as a novel proteolytic component of the DNA damage response. (PMID:28866241)
• APEH knockdown abrogated RAS-RAF-MAPK signaling in cells expressing the constitutively active (oncogenic) mutant of KRAS (KRASG12V), and selectively inhibited the proliferation of KRAS-transformed pancreatic cancer cells. Taken together, these results identify APEH as a novel drug target for a potential anti-KRAS therapeutic. (PMID:31266814)
• Selective inhibition of acylpeptide hydrolase in SAOS-2 osteosarcoma cells: is this enzyme a viable anticancer target? (PMID:33471263)
• Deubiquitinase UCHL1 Maintains Protein Homeostasis through the PSMA7-APEH-Proteasome Axis in High-grade Serous Ovarian Carcinoma. (PMID:33753553)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	apeh	ENSDARG00000008703
mus_musculus	Apeh	ENSMUSG00000032590
rattus_norvegicus	Apeh	ENSRNOG00000029572
caenorhabditis_elegans		WBGENE00001058

Paralogs (6): DPP8 (ENSG00000074603), FAP (ENSG00000078098), DPP6 (ENSG00000130226), DPP9 (ENSG00000142002), DPP10 (ENSG00000175497), DPP4 (ENSG00000197635)

Protein

Protein identifiers

Acylamino-acid-releasing enzyme — P13798 (reviewed: P13798)

Alternative names: Acyl-peptide hydrolase, Acylaminoacyl-peptidase, Oxidized protein hydrolase

All UniProt accessions (9): C9JIF9, C9JLK2, F8WBC4, F8WEH5, H0YFE5, H7C1U0, H7C273, H7C393, P13798

UniProt curated annotations — full annotation on UniProt →

Function. Aminopeptidase involved in the degradation of N(alpha)-acylated peptides. Displays exopeptidase activity toward N-formyl and N-acetyl peptides with a preference for dipeptide substrates. Catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser. Hydrolyzes N-formylated peptides likely arising from N-terminal proteolytic cleavage of bacterial and mitochondrial proteins. May act sequentially with ACY1 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. Displays endopeptidase activity involved in the degradation of oxidized and glycated proteins.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in erythrocytes (at protein level).

Activity regulation. Homotetramerization is required for activity. Tetramerization results in the formation of a gated channel which is involved in substrate selection and substrate access to the catalytic sites.

Similarity. Belongs to the peptidase S9C family.

RefSeq proteins (1): NP_001631* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001375	Peptidase_S9_cat	Domain
IPR002471	Pept_S9_AS	Active_site
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR045550	AARE_N	Domain

Pfam: PF00326, PF19283

Enzyme classification (BRENDA):

• EC 3.4.19.1 — acylaminoacyl-peptidase (BRENDA: 23 organisms, 219 substrates, 203 inhibitors, 92 Km, 71 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
AC-LEU-P-NITROANILIDE	0.0091–1.76	12
N-ACETYL-LEU-P-NITROANILIDE	0.4–10.5	7
P-NITROPHENYL CAPRYLATE	35.7–114.6	7
2-AMINOBENZOYL-ALA-LEU-PHE-GLN-GLY-PRO-PHE(NO2)-	0.0013–0.0071	3
ACETYL-ALA-4-NITROANILIDE	0.12–20.2	3
N-ACETYL-ALA-P-NITROANILIDE	0.006–4.6	3
N-ACETYL-L-ALA-4-NITROANILIDE	0.8–0.83	3
N-ACETYL-MET-ALA	0.49–0.68	3
N-ACETYL-PHE-2-NAPHTHYLAMIDE	0.0057–0.1	3
ACETYL-ALA-ALA	7.6–8.6	2
ACETYL-ALA-ALA-ALA-ALA	13–15.2	2
ACETYL-LEU-4-NITROANILIDE	11–12.9	2
ACETYL-PHE-2-NAPHTHYLAMIDE	0.0082–0.1	2
N-ACETYL-ALA-ALA-ALA-ALA	0.8–2.1	2
N-ACETYL-L-ALANYL 4-NITROANILIDE	0.8–11.4	2

Catalyzed reactions (Rhea), 8 shown:

• N(alpha)-formyl-L-methionyl-L-leucyl-L-phenylalanine + H2O = L-leucyl-L-phenylalanine + N(alpha)-formyl-L-methionine (RHEA:83443)
• N(alpha)-formyl-L-methionyl-L-phenylalanine + H2O = N(alpha)-formyl-L-methionine + L-phenylalanine (RHEA:83487)
• N(alpha)-formyl-L-methionyl-L-alanine + H2O = N(alpha)-formyl-L-methionine + L-alanine (RHEA:83491)
• N(alpha)-formyl-L-methionyl-L-alanyl-L-serine + H2O = L-alanyl-L-serine + N(alpha)-formyl-L-methionine (RHEA:83495)
• N(alpha)-formyl-L-methionyl-L-serine + H2O = N(alpha)-formyl-L-methionine + L-serine (RHEA:83499)
• N(alpha)-acetyl-L-methionyl-L-alanyl-L-serine + H2O = L-alanyl-L-serine + N-acetyl-L-methionine (RHEA:83503)
• N(alpha)-acetyl-L-alanyl-L-alanine + H2O = N(alpha)-acetyl-L-alanine + L-alanine (RHEA:83507)
• N(alpha)-acetyl-L-alanyl-L-alanyl-L-alanine + H2O = N(alpha)-acetyl-L-alanine + L-alanyl-L-alanine (RHEA:83511)

UniProt features (13 total): sequence conflict 5, active site 3, modified residue 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13798-F1	93.58	0.89

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 (3): 587 (charge relay system); 675 (charge relay system); 707 (charge relay system)

Post-translational modifications (3): 1, 185, 187

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 101 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_TRANSLATIONAL_TERMINATION, GOBP_TRANSLATION, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_AMIDE_METABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, DOUGLAS_BMI1_TARGETS_UP, GOCC_SECRETORY_VESICLE, GOBP_PROTEOLYSIS, GARY_CD5_TARGETS_UP, SCGGAAGY_ELK1_02, KIM_WT1_TARGETS_DN, MGGAAGTG_GABP_B

GO Biological Process (3): translational termination (GO:0006415), proteolysis (GO:0006508), amyloid-beta metabolic process (GO:0050435)

GO Molecular Function (8): RNA binding (GO:0003723), serine-type endopeptidase activity (GO:0004252), omega peptidase activity (GO:0008242), identical protein binding (GO:0042802), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), cytosol (GO:0005829), nuclear membrane (GO:0031965), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Innate Immune System	1
Translation	1
Immune System	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
peptidase activity	2
translation	1
protein-containing complex disassembly	1
protein metabolic process	1
metabolic process	1
nucleic acid binding	1
endopeptidase activity	1
serine-type peptidase activity	1
protein binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine hydrolase activity	1
catalytic activity	1
cytoplasm	1
nucleus	1
nuclear envelope	1
organelle membrane	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APEH	PREP	P48147	917
APEH	NCSTN	Q92542	902
APEH	ACY1	Q03154	880
APEH	MST1	P26927	836
APEH	PSENEN	Q9NZ42	821
APEH	DPP4	P27487	733
APEH	NR3C2	P08235	720
APEH	MSRA	Q9UJ68	697
APEH	GLB1	P16278	695
APEH	ARR3	P36575	684
APEH	ASPA	P45381	664
APEH	UBAC1	Q9BSL1	608
APEH	CD248	Q9HCU0	594
APEH	PGPEP1	Q9NXJ5	589
APEH	OXA1L	Q15070	581

IntAct

43 interactions, top by confidence:

A	B	Type	Score
APEH	APEH	psi-mi:“MI:0915”(physical association)	0.800
IST1	APEH	psi-mi:“MI:0915”(physical association)	0.750
APEH	IST1	psi-mi:“MI:0915”(physical association)	0.750
APEH	LGALS8	psi-mi:“MI:0915”(physical association)	0.670
LGALS8	APEH	psi-mi:“MI:0915”(physical association)	0.670
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
APEH	IST1	psi-mi:“MI:0915”(physical association)	0.560
PCNA	APEH	psi-mi:“MI:0915”(physical association)	0.370
APEH	UBA5	psi-mi:“MI:0915”(physical association)	0.370
ORF10	NUP42	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
C3orf62	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
IFTAP	GNPAT	psi-mi:“MI:0914”(association)	0.350
	KIF5C	psi-mi:“MI:0914”(association)	0.350
NUTM2F	IRF6	psi-mi:“MI:0914”(association)	0.350
	BANF1	psi-mi:“MI:0914”(association)	0.350
SUZ12	TNPO2	psi-mi:“MI:0914”(association)	0.350
RMC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): APEH (Two-hybrid), LGALS8 (Two-hybrid), IST1 (Two-hybrid), APEH (Affinity Capture-RNA), APEH (Affinity Capture-RNA), APEH (Two-hybrid), UBA5 (Two-hybrid), IST1 (Two-hybrid), APEH (Co-fractionation), APEH (Co-fractionation), CNOT7 (Co-fractionation), USP39 (Co-fractionation), APEH (Affinity Capture-MS), APEH (Affinity Capture-MS), APEH (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QP51, E9PYK3, E9Q4Z2, G1SPE9, O00763, O15228, O23617, P13676, P13798, P19205, P25154, P35574, P80227, P83006, P98192, Q10MJ1, Q2PQH8, Q338C0, Q496Z0, Q5EBA1, Q5IH13, Q5IH14, Q5R5S1, Q5U5V2, Q5ZIB9, Q641Y5, Q6V1X1, Q6YXW6, Q80YA7, Q80YD1, Q80ZK9, Q86TI2, Q8BVG4, Q8C0P5, Q8C5P5, Q8IYB8, Q8K4M9, Q8N5D0, Q8R146, Q8VZF3

Diamond homologs: P13676, P13798, P19205, P25154, P39839, P80227, Q0IXP9, Q338C0, Q84LM4, Q8R146, V5YMB3, A0S5W0, A2QZF1, A5F753, A7UKV4, B6V869, C3LND9, C5FH88, D4ARB1, D4D5P5, Q0C8V9, Q0VRJ2, Q3LS63, Q5BA58, Q7MJ87, Q8DAM3, Q8J1L4, Q8J1M3, Q8UEU8, Q9KR11, A0A2R8QP51, B2RJX3, Q7MUW6, Q86TI2, Q8BVG4, P34422

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	68
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3391820	GRCh37/hg19 3p21.31-21.2(chr3:48855503-51285217)x3	Likely pathogenic

SpliceAI

3443 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49674590:G:GG	donor_gain	1.0000
3:49674608:G:GT	donor_gain	1.0000
3:49674622:G:GG	donor_gain	1.0000
3:49675182:GA:G	acceptor_gain	1.0000
3:49675291:G:GG	donor_gain	1.0000
3:49675305:GGGGA:G	donor_gain	1.0000
3:49675306:GGGA:G	donor_gain	1.0000
3:49675306:GGGAG:G	donor_gain	1.0000
3:49675307:G:GT	donor_gain	1.0000
3:49675307:G:T	donor_gain	1.0000
3:49675307:GGA:G	donor_gain	1.0000
3:49675308:GA:G	donor_gain	1.0000
3:49675308:GAG:G	donor_gain	1.0000
3:49675310:G:GG	donor_gain	1.0000
3:49675321:G:GT	donor_gain	1.0000
3:49675684:A:AG	acceptor_gain	1.0000
3:49675684:AT:A	acceptor_gain	1.0000
3:49675685:T:A	acceptor_gain	1.0000
3:49675685:T:G	acceptor_gain	1.0000
3:49675691:C:G	acceptor_gain	1.0000
3:49675692:A:AC	acceptor_loss	1.0000
3:49675692:A:AG	acceptor_gain	1.0000
3:49675692:AGACT:A	acceptor_gain	1.0000
3:49675693:G:C	acceptor_loss	1.0000
3:49675693:G:GT	acceptor_gain	1.0000
3:49675693:GA:G	acceptor_gain	1.0000
3:49675693:GAC:G	acceptor_gain	1.0000
3:49675693:GACT:G	acceptor_gain	1.0000
3:49675693:GACTG:G	acceptor_gain	1.0000
3:49675784:GGAG:G	donor_gain	1.0000

AlphaMissense

4769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49676076:T:A	W155R	0.999
3:49676076:T:C	W155R	0.999
3:49676405:T:A	W212R	0.999
3:49676405:T:C	W212R	0.999
3:49683076:G:C	D675H	0.999
3:49675185:T:A	W50R	0.998
3:49675185:T:C	W50R	0.998
3:49676407:G:C	W212C	0.998
3:49676407:G:T	W212C	0.998
3:49676615:T:A	W251R	0.998
3:49676615:T:C	W251R	0.998
3:49676697:G:C	R278P	0.998
3:49682352:C:A	N536K	0.998
3:49682352:C:G	N536K	0.998
3:49682363:C:T	S540F	0.998
3:49682723:G:C	D624H	0.998
3:49683077:A:C	D675A	0.998
3:49683077:A:T	D675V	0.998
3:49683082:C:A	R677S	0.998
3:49676103:T:G	Y164D	0.997
3:49676109:G:C	A166P	0.997
3:49676110:C:A	A166E	0.997
3:49676406:G:C	W212S	0.997
3:49676675:G:C	G271R	0.997
3:49676689:C:G	C275W	0.997
3:49676947:A:C	S308R	0.997
3:49676949:C:A	S308R	0.997
3:49676949:C:G	S308R	0.997
3:49678896:T:A	W369R	0.997
3:49678896:T:C	W369R	0.997

dbSNP variants (sampled 300 via entrez): RS1000307460 (3:49678099 G>A), RS1001094509 (3:49683031 A>G,T), RS1001278303 (3:49677084 G>C), RS1002232678 (3:49679485 G>A,T), RS1002238025 (3:49675495 C>G,T), RS1002326577 (3:49673456 C>G,T), RS1002378855 (3:49673161 A>G), RS1003204897 (3:49680979 G>A,C), RS1003222546 (3:49680965 C>G,T), RS1003359683 (3:49674849 G>C), RS1003818298 (3:49674507 G>A), RS1004677679 (3:49683818 T>G), RS1004692074 (3:49676924 T>C,G), RS1005605905 (3:49674164 C>T), RS1005939715 (3:49672105 A>T)

Disease associations

OMIM: gene MIM:102645 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000964_6	Ulcerative colitis	2.000000e-17
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005951_49	Body mass index	1.000000e-08
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST006950_51	Feeling worry	2.000000e-09
GCST006952_17	Feeling tense	3.000000e-09
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST009523_18	Household income	7.000000e-11
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009592	social interaction measurement
EFO:0009589	worry measurement
EFO:0009596	feeling tense measurement
EFO:0004337	intelligence
EFO:0009695	household income
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741174 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3816877	APEH		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S9: Prolyl oligopeptidase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
ARI-3099	Inhibition	6.98	pIC50

ChEMBL bioactivities

4 potent at pChembl≥5 of 5 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.63	Kd	23.59	nM	CHEMBL3752910
7.55	ED50	28.18	nM	CHEMBL3752910
5.50	Kd	3140	nM	CHEMBL5653589
5.43	ED50	3751	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 13 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147872: Binding affinity to human APEH incubated for 45 mins by Kinobead based pull down assay	kd	0.0236	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147872: Binding affinity to human APEH incubated for 45 mins by Kinobead based pull down assay	kd	3.1399	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
cobaltous chloride	decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide	decreases activity	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	decreases activity	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
valproic acid glucuronide	increases metabolic processing, decreases reaction	1
phenylsaligenin cyclic phosphate	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738450	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify inhibitors of the protein methylesterase PME-1: Gel-based Activity-Based Protein Profiling (ABPP) IC50. (Class of assay: confirmatory) [Related pubchem assay	PubChem BioAssay data set
CHEMBL2027538	Binding	Inhibition of APEH in human HeLa cells after 24 hrs	Small peptide inhibitors of acetyl-peptide hydrolase having an uncommon mechanism of inhibition and a stable bent conformation. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2RT	Abcam HEK293T APEH KO	Transformed cell line	Female
CVCL_E1QJ	HAP1 APEH (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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