ANPEP

Summary

ANPEP (alanyl aminopeptidase, membrane, HGNC:500) is a protein-coding gene on chromosome 15q26.1, encoding Aminopeptidase N (P15144). Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases.

Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma.

Source: NCBI Gene 290 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 167 total — 1 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:500
Approved symbol	ANPEP
Name	alanyl aminopeptidase, membrane
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	LAP1, gp150, p150, AP-N, hAPN
Ensembl gene	ENSG00000166825
Ensembl biotype	protein_coding
OMIM	151530
Entrez	290

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000300060, ENST00000558177, ENST00000558740, ENST00000559761, ENST00000559874, ENST00000559887, ENST00000560028, ENST00000560030, ENST00000560137, ENST00000679248, ENST00000889294, ENST00000889295, ENST00000889296, ENST00000889297, ENST00000889298, ENST00000889299, ENST00000889300, ENST00000889301, ENST00000970307

RefSeq mRNA: 3 — MANE Select: NM_001150 NM_001150, NM_001381923, NM_001381924

CCDS: CCDS10356

Canonical transcript exons

ENST00000300060 — 21 exons

Exon	Start	End
ENSE00001106972	89803889	89804002
ENSE00001106975	89805078	89805217
ENSE00001106994	89790460	89790541
ENSE00001107011	89805321	89805463
ENSE00001162447	89784895	89785501
ENSE00001183169	89805970	89806806
ENSE00001263117	89803647	89803790
ENSE00001321392	89793035	89793126
ENSE00001479879	89814772	89814852
ENSE00003461993	89803442	89803507
ENSE00003482487	89799426	89799559
ENSE00003525100	89790953	89791093
ENSE00003571108	89799260	89799315
ENSE00003601639	89804253	89804407
ENSE00003631491	89792160	89792327
ENSE00003643482	89797575	89797722
ENSE00003654877	89801435	89801607
ENSE00003659192	89801111	89801187
ENSE00003671304	89804491	89804617
ENSE00003680804	89792452	89792562
ENSE00003684209	89803239	89803304

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.4579 / max 14043.7427, expressed in 1226 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151538	50.1667	1151
151534	20.8783	589
151540	3.7409	900
151542	1.2825	565
151510	0.5084	271
151501	0.4591	253
151539	0.4541	259
151514	0.4362	210
151504	0.3771	200
151541	0.3306	179

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.87	gold quality
duodenum	UBERON:0002114	99.83	gold quality
body of pancreas	UBERON:0001150	99.53	gold quality
ileal mucosa	UBERON:0000331	99.43	gold quality
mucosa of transverse colon	UBERON:0004991	99.26	gold quality
right lobe of liver	UBERON:0001114	98.92	gold quality
stromal cell of endometrium	CL:0002255	98.80	gold quality
gall bladder	UBERON:0002110	98.66	gold quality
liver	UBERON:0002107	98.10	gold quality
adult mammalian kidney	UBERON:0000082	98.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.59	gold quality
pancreas	UBERON:0001264	97.25	gold quality
small intestine	UBERON:0002108	97.14	gold quality
adult organism	UBERON:0007023	97.12	gold quality
blood	UBERON:0000178	96.64	gold quality
granulocyte	CL:0000094	96.52	gold quality
monocyte	CL:0000576	96.33	gold quality
leukocyte	CL:0000738	96.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.09	gold quality
mononuclear cell	CL:0000842	96.02	gold quality
minor salivary gland	UBERON:0001830	95.51	gold quality
nasal cavity epithelium	UBERON:0005384	95.30	gold quality
rectum	UBERON:0001052	95.17	gold quality
right lung	UBERON:0002167	95.16	gold quality
pancreatic ductal cell	CL:0002079	95.00	gold quality
nephron tubule	UBERON:0001231	94.91	gold quality
kidney	UBERON:0002113	94.80	gold quality
kidney epithelium	UBERON:0004819	94.65	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.56	gold quality
transverse colon	UBERON:0001157	94.02	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	3872.32
E-CURD-122	yes	3488.82
E-CURD-46	yes	2505.43
E-MTAB-9543	yes	2287.84
E-MTAB-9906	yes	923.28
E-GEOD-84465	yes	550.09
E-CURD-112	yes	411.83
E-GEOD-81547	yes	411.76
E-GEOD-149689	yes	337.05
E-MTAB-8142	yes	48.63
E-MTAB-5061	yes	21.88
E-HCAD-13	yes	21.68
E-MTAB-10553	yes	20.49
E-HCAD-9	yes	10.70
E-ENAD-27	yes	6.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DMTF1, ETS1, ETS2, HNF1A, IRX1, MAF, MYB, MYBL2, ZFHX3

miRNA regulators (miRDB)

30 targeting ANPEP, 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-4692	100.00	67.32	2066
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-193A-5P	95.70	65.33	613

Literature-anchored findings (GeneRIF, showing 40)

• data demonstrate that the glycosylation of aminopeptidase N at N291 blocks human coronavirus-229E infection (PMID:11774469)
• tested the hypothesis that CD13 influences proliferation of monocytoid cells by retarding the velocity of the cell cycle (PMID:11999577)
• CD13/APN is an important target of Ras signaling in angiogenesis and is a limiting factor in angiogenic progression. (PMID:12406907)
• inhibiting CD13/aminopeptidase N on the cell-surface of acute promyelocytic leukemia cells increases ATRA-induced differentiation (PMID:12443882)
• Binding of aminopeptidase N may trigger conformational changes in the coronavirus viral spike protein that facilitate virus entry. (PMID:12634402)
• DPPIV acts synergistically with this protein to regulate T cell function. (PMID:12675232)
• phosphorylation of Ets-2 by RAS/MAPK is a prerequisite for CD13/APN endothelial induction (PMID:14507917)
• CD13 has a characteristic canalicular distribution pattern and may have a role in cell polarization and bile compartmentalization in hepatocellular carcinomas (PMID:14767532)
• The activity of urinary alanine aminopeptidase as an index of alcohol-related kidney impairment is a valuable complement to the existing set of markers of chronic alcohol abuse. (PMID:15166647)
• HCoV-229E(human coronavirus) first binds to CD13 in the Triton X-100-resistant microdomain, then clusters CD13 by cross-linking, and thereby reaches the caveolar region before entering cells. (PMID:15280478)
• CD13 acts as a signal regulator of FcgammaR function. (PMID:15758076)
• TAL6 and CD13 can form a complex on lung cancer cells; these molecules can modulate cell migration and invasion, and the influence of CD13 on cell motility does not strictly depend on its aminopeptidase activity (PMID:15812828)
• Although hAPN-transgenic mice were resistant to HCoV-229E in vivo, primary embryonic cells and bone marrow dendritic cells were infected in vitro (PMID:15840518)
• results imply a novel functional role of CD13 and Fc gamma receptors as members of a multimeric receptor complex (PMID:15883031)
• Data identify CD13, CD107a, and CD164 as novel basophil-activation antigens. (PMID:15916720)
• Aspirin may exert its anti-atherothrombotic effects in part via the inhibition of thrombin action by up-regulating APN/CD13 on endothelial cells. (PMID:16216591)
• Findings suggest that APN is a multifunctional protein with important roles in vascular endothelial morphogenesis during angiogenesis. (PMID:16466852)
• Mutation in aminopeptidase N (CD13) isolated from a patient suffering from leukemia leads to an arrest in the endoplasmic reticulum (PMID:16469741)
• APN/CD13 regulates TNFalpha-induced apoptosis via inhibition of TNFRI shedding (PMID:16533817)
• bFGF expression upregulates CD13 expression in human melanoma cells and results in enhanced invasive capacity and metastatic behaviour of human melanoma cells. (PMID:16685268)
• Our data provide first evidence for a functional role of DP IV and APN in the sebaceous gland apparatus and for their inhibitors, used alone or in combination, as completely new substances possibly affecting acne pathogenesis in a therapeutic manner. (PMID:16778789)
• The expression of APN/CD13 for patients with NSCLC to be associated with a poor prognosis and angiogenesis. This is the first study to show the relationship between the expression of APN/CD13 and the prognosis of patients with NSCLC. (PMID:16818694)
• RECK protein interacts with MT1-MMP and CD13/aminopeptidase N and modulates their endocytic pathways (PMID:17329256)
• CD13 rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms that had reduced binding, signaling, and chemotactic properties for lymphocytes and CXCR3- or CXCR7-transfected cells. (PMID:17363734)
• CD13 functions as a novel modulator of signal transduction and cell motility via its influence on specific plasma membrane organization, thus regulating angiogenesis. (PMID:17363739)
• Overexpression of ANPEP is associated with Barrett’s adenocarcinomas (PMID:17636545)
• There was a positive correlation between APN/CD13 expression and migratory potential in various ovarian carcinoma cell lines with accordingly enhanced secretion of endogenous MMP-2. (PMID:17655775)
• Expression is frequenty decreased in chronic myelogenous leukemia. (PMID:17662271)
• Finally, exogenous addition of galectin-3 into HUVECs induced angiogenesis in an APN-dependent manner. (PMID:17888402)
• CD13 transcription is regulated by MAF via an atypical response element. (PMID:17897790)
• Enkephalin-degrading enzymes are present in human semen and may be involved in the control of sperm motility, mainly by the regulation of endogenous opioid peptides. (PMID:17953966)
• Data show that aminopeptidase N (APA) plays important roles in the regulation of blood pressure under both the physiological and pathological conditions. (PMID:17999179)
• Data support that APN plays important roles in the regulation of arterial blood pressure and the pathogenesis of hypertension. (PMID:18008160)
• CD13 was expressed in 73% of acute myeloid leukemia patients, CD15 was expressed in 43% of patients, CD33 was expressed in 64% of patients, and CD34 was expressed in 66% of patients. (PMID:18085638)
• APN/CD13 inhibition by Ubenimex enhances radiosensitivity; APN/CD13 plays an important role in tumor progression in several human malignancies (PMID:18366676)
• Data suggest that detection of CD2 or CD13 expression in chronic lymphocytic leukemia (CLL) suggests familial CLL, and that CD38 expression does not carry the negative prognosis observed in sporadic CLL. (PMID:18431797)
• New direction for CD13 biology, where cell surface molecules act as true molecular interfaces that induce and participate in critical inflammatory cell interactions. (PMID:18495788)
• Demonstrates expression of immune system in granulocytes after heart surgery. (PMID:18605079)
• Angiotensin III and aminopeptidase A and N, related converting enzymes, contribute to cell proliferation of prostate cancer and may be implicated in cancer progression. (PMID:18677709)
• CD13 and/or CD33 are sensitive but not entirely specific markers of anaplastic lymphoma kinase anaplastic large cell lymphomas and should not be misinterpreted as indicating myeloid sarcoma. (PMID:18794057)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	anpepa	ENSDARG00000036809
danio_rerio	anpepb.2	ENSDARG00000097285
danio_rerio	anpepb.1	ENSDARG00000103878
mus_musculus	Anpep	ENSMUSG00000039062
rattus_norvegicus	Anpep	ENSRNOG00000014610
drosophila_melanogaster	CG7653	FBGN0028935
drosophila_melanogaster	CG9806	FBGN0030222
drosophila_melanogaster	CG2111	FBGN0030223
drosophila_melanogaster	CG6071	FBGN0036186
drosophila_melanogaster	CG5849	FBGN0038897
drosophila_melanogaster	CG3502	FBGN0046253
drosophila_melanogaster	CG31233	FBGN0051233
drosophila_melanogaster	CG31343	FBGN0051343
drosophila_melanogaster	CG31445	FBGN0051445
drosophila_melanogaster	SP1029	FBGN0263236
drosophila_melanogaster	CG46339	FBGN0285963
caenorhabditis_elegans	F49B2.6	WBGENE00009865
caenorhabditis_elegans		WBGENE00011587
caenorhabditis_elegans		WBGENE00012776

Paralogs (11): TRHDE (ENSG00000072657), LTA4H (ENSG00000111144), LNPEP (ENSG00000113441), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), AOPEP (ENSG00000148120), ERAP1 (ENSG00000164307), ERAP2 (ENSG00000164308), LVRN (ENSG00000172901), RNPEP (ENSG00000176393)

Protein

Protein identifiers

Aminopeptidase N — P15144 (reviewed: P15144)

Alternative names: Alanyl aminopeptidase, Aminopeptidase M, Microsomal aminopeptidase, Myeloid plasma membrane glycoprotein CD13, gp150

All UniProt accessions (5): P15144, H0YKT6, H0YLZ8, H0YM04, H0YMC1

UniProt curated annotations — full annotation on UniProt →

Function. Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis and promote cholesterol crystallization. May have a role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 and regulating its activity. (Microbial infection) Acts as a receptor for human coronavirus 229E/HCoV-229E. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein. (Microbial infection) Mediates as well Human cytomegalovirus (HCMV) infection.

Subunit / interactions. Homodimer. Interacts with SLC6A19. (Microbial infection) Interacts with the S1 domain of human coronavirus 229E/HCoV-229E spike protein.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in epithelial cells of the kidney, intestine, and respiratory tract; granulocytes, monocytes, fibroblasts, endothelial cells, cerebral pericytes at the blood-brain barrier, synaptic membranes of cells in the CNS. Also expressed in endometrial stromal cells, but not in the endometrial glandular cells. Found in the vasculature of tissues that undergo angiogenesis and in malignant gliomas and lymph node metastases from multiple tumor types but not in blood vessels of normal tissues. A soluble form has been found in plasma. It is found to be elevated in plasma and effusions of cancer patients.

Post-translational modifications. Sulfated. N- and O-glycosylated. May undergo proteolysis and give rise to a soluble form.

Cofactor. Binds 1 zinc ion per subunit.

Induction. Estradiol and IL8/interleukin-8 decrease enzymatic activity in vitro in endometrial stromal cells by 40% and 30%, respectively.

Miscellaneous. Found to serve as a receptor for tumor-homing peptides, more specifically NGR peptides. It could serve thus as a target for delivering drugs into tumors. Concentration in human hepatic bile, varies from 17.3 to 57.6 micrograms/ml.

Similarity. Belongs to the peptidase M1 family.

RefSeq proteins (3): NP_001141, NP_001368852, NP_001368853 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001930	Peptidase_M1	Family
IPR014782	Peptidase_M1_dom	Domain
IPR024571	ERAP1-like_C_dom	Domain
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR034016	M1_APN-typ	Family
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR045357	Aminopeptidase_N-like_N	Domain
IPR050344	Peptidase_M1_aminopeptidases	Family

Pfam: PF01433, PF11838, PF17900

Enzyme classification (BRENDA):

• EC 3.4.11.2 — membrane alanyl aminopeptidase (BRENDA: 57 organisms, 398 substrates, 1043 inhibitors, 151 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-LEU-4-NITROANILIDE	0.17–9.23	8
L-ALA-4-NITROANILIDE	0.032–14	7
ALA-2-NAPHTHYLAMIDE	0.038–1	6
L-ARG-2-NAPHTHYLAMIDE	0.025–0.099	5
LEU-2-NAPHTHYLAMIDE	0.02–0.095	5
L-LYS-4-NITROANILIDE	0.07–0.382	4
GLY-2-NAPHTHYLAMIDE	0.74–1	3
GLY-7-AMIDO-4-METHYLCOUMARIN	0.0579–0.31	3
L-ALA-7-AMIDO-4-METHYLCOUMARIN	0.011–0.139	3
L-LEU-7-AMIDO-4-METHYLCOUMARIN	0.0329–0.27	3
L-MET-7-AMIDO-4-METHYLCOUMARIN	0.086–0.34	3
ALA-4-METHYLCOUMARYL-7-AMIDE	0.197–1.276	2
ALANYL-4-METHYLCOUMARYL-7-AMIDE	0.197–1.276	2
ARG-4-METHYLCOUMARYL-7-AMIDE	0.308–0.98	2
ARGINYL-4-METHYLCOUMARYL-7-AMIDE	0.308–0.98	2

UniProt features (138 total): helix 43, strand 33, turn 11, glycosylation site 10, sequence variant 9, mutagenesis site 8, binding site 4, modified residue 4, region of interest 4, topological domain 2, disulfide bond 2, sequence conflict 2, initiator methionine 1, chain 1, active site 1, site 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
7AEW	X-RAY DIFFRACTION	1.2
6XWD	X-RAY DIFFRACTION	1.6
4FYT	X-RAY DIFFRACTION	1.85
4FYQ	X-RAY DIFFRACTION	1.9
4FYR	X-RAY DIFFRACTION	1.91
4FYS	X-RAY DIFFRACTION	2.01
6U7G	X-RAY DIFFRACTION	2.35
5LHD	X-RAY DIFFRACTION	2.6
6U7F	X-RAY DIFFRACTION	2.75
9CAM	ELECTRON MICROSCOPY	2.96
6U7E	X-RAY DIFFRACTION	3
7VPQ	X-RAY DIFFRACTION	3.1
9CAO	ELECTRON MICROSCOPY	3.14
6ATK	X-RAY DIFFRACTION	3.5
8WDE	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15144-F1	93.55	0.86

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): 389 (proton acceptor); 477 (transition state stabilizer)

Ligand- & substrate-binding residues (4): 352–356; 388; 392; 411

Post-translational modifications (4): 176, 419, 424, 913

Disulfide bonds (2): 761–768, 798–834

Glycosylation sites (10): 128, 234, 265, 319, 527, 573, 625, 681, 735, 818

Mutagenesis-validated functional residues (8):

Position	Phenotype
288–295	no change in receptor activity and hcov-229e infection.
288–295	complete loss of receptor activity and blocks hcov-229e infection. no loss of enzymatic activity.
291–293	complete loss of receptor activity and blocks hcov-229e infection. no loss of enzymatic activity.
291	no change of receptor activity and hcov-229e infection.
293	no change of receptor activity and hcov-229e infection.
392	loss of aminopeptidase activity.
818	very low receptor activity and hcov-229e infection.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 331 (showing top): MODULE_172, MODULE_52, MODULE_516, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_BLOOD_PRESSURE, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_45, MODULE_64

GO Biological Process (6): angiogenesis (GO:0001525), angiotensin maturation (GO:0002003), cell differentiation (GO:0030154), peptide catabolic process (GO:0043171), proteolysis (GO:0006508), symbiont entry into host cell (GO:0046718)

GO Molecular Function (10): virus receptor activity (GO:0001618), aminopeptidase activity (GO:0004177), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), alanyl aminopeptidase activity (GO:0016285), signaling receptor activity (GO:0038023), metalloaminopeptidase activity (GO:0070006), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), lysosomal membrane (GO:0005765), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), secretory granule membrane (GO:0030667), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Peptide hormone metabolism	1
Innate Immune System	1
Immune System	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aminopeptidase activity	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of angiotensin levels in blood	1
peptide hormone processing	1
cellular developmental process	1
peptide metabolic process	1
catabolic process	1
protein metabolic process	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
exopeptidase activity	1
peptidase activity	1
transition metal ion binding	1
molecular transducer activity	1
metalloexopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANPEP	RTN4R	Q9BZR6	996
ANPEP	CD7	P09564	963
ANPEP	CD33	P20138	952
ANPEP	FCGR3A	P08637	950
ANPEP	ACE2	Q9BYF1	936
ANPEP	FCGR3B	O75015	930
ANPEP	DPP4	P27487	921
ANPEP	KIT	P10721	919
ANPEP	ITGAM	P11215	913
ANPEP	MME	P08473	893
ANPEP	OPRPN	P85047	887
ANPEP	CD34	P28906	879
ANPEP	FUT4	P22083	872
ANPEP	ALB	P02768	865
ANPEP	CD19	P15391	853

IntAct

28 interactions, top by confidence:

A	B	Type	Score
CD81	ANPEP	psi-mi:“MI:0914”(association)	0.530
TSPAN12	ADAM10	psi-mi:“MI:0914”(association)	0.500
ANPEP	S	psi-mi:“MI:0407”(direct interaction)	0.440
Cep76	DCTN2	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
	MYO1C	psi-mi:“MI:0914”(association)	0.350
ERBB2	DNM1L	psi-mi:“MI:0914”(association)	0.350
ATF1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATF2	ABLIM1	psi-mi:“MI:0914”(association)	0.350
CEBPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
CEBPD	ESYT2	psi-mi:“MI:0914”(association)	0.350
PPARA	ESYT2	psi-mi:“MI:0914”(association)	0.350
STAT3	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
SFN	ANPEP	psi-mi:“MI:0914”(association)	0.350
pulB	ANPEP	psi-mi:“MI:0915”(physical association)	0.000
ANPEP	pyrG	psi-mi:“MI:0915”(physical association)	0.000
ANPEP	gltX	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (198): ANPEP (Two-hybrid), ANPEP (Affinity Capture-MS), ANPEP (Protein-RNA), ANPEP (Affinity Capture-MS), ANPEP (Affinity Capture-MS), ANPEP (Affinity Capture-MS), ANPEP (Affinity Capture-MS), ANPEP (Affinity Capture-MS), ANPEP (Affinity Capture-MS), ANPEP (Affinity Capture-MS), ADAM10 (Affinity Capture-MS), COCH (Affinity Capture-MS), XPOT (Affinity Capture-MS), CALU (Affinity Capture-MS), CPD (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4K692, A5HUI5, B2RQR8, D3UW23, F1N476, O16796, O44857, O95672, P07861, P08049, P08473, P0C1T0, P0DPD6, P0DPD9, P15144, P15145, P15684, P16406, P42891, P42892, P42893, P50123, P97739, Q07075, Q10715, Q10751, Q18673, Q22523, Q32LQ0, Q495T6, Q4PZA2, Q56H28, Q56NL1, Q58DD0, Q5EGZ1, Q5RE69, Q5RFN1, Q61391, Q6Q4G4, Q8IS64

Diamond homologs: A0A6J2ATK2, A6NEC2, A6QPT7, M3XFH7, O57579, P15144, P15145, P15541, P15684, P46557, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10736, Q10836, Q2KHK3, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q8C129, Q8K093, Q95334, Q9EQH2, Q9JJ22, Q9UIQ6, Q9UKU6, A5HUI5, D3UW23, O93654, O93655, P0DQU2, P16406, P32454, P37893

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Tosedostat	down-regulates	ANPEP	“chemical inhibition”
IRX1	“up-regulates quantity by expression”	ANPEP	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by Interleukins	5	13.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	115
Likely benign	16
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4279473	GRCh37/hg19 15q26.1(chr15:90281956-90331282)x1	Pathogenic

SpliceAI

3280 predictions. Top by Δscore:

Variant	Effect	Δscore
15:89785498:CCAG:C	acceptor_gain	1.0000
15:89785499:CAG:C	acceptor_gain	1.0000
15:89785499:CAGC:C	acceptor_gain	1.0000
15:89785500:AG:A	acceptor_gain	1.0000
15:89785500:AGC:A	acceptor_loss	1.0000
15:89785502:C:CA	acceptor_loss	1.0000
15:89785502:C:CC	acceptor_gain	1.0000
15:89785506:C:CT	acceptor_gain	1.0000
15:89785506:C:T	acceptor_gain	1.0000
15:89785507:A:T	acceptor_gain	1.0000
15:89786940:A:C	acceptor_gain	1.0000
15:89790455:CTTAC:C	donor_loss	1.0000
15:89790456:TTA:T	donor_loss	1.0000
15:89790457:TACCT:T	donor_loss	1.0000
15:89790458:ACC:A	donor_loss	1.0000
15:89790459:C:CT	donor_loss	1.0000
15:89790459:CCTG:C	donor_gain	1.0000
15:89790537:CATAA:C	acceptor_gain	1.0000
15:89790538:ATAA:A	acceptor_gain	1.0000
15:89790539:TAA:T	acceptor_gain	1.0000
15:89790540:AA:A	acceptor_gain	1.0000
15:89790540:AACT:A	acceptor_loss	1.0000
15:89790541:ACTG:A	acceptor_loss	1.0000
15:89790542:C:CC	acceptor_gain	1.0000
15:89790542:C:T	acceptor_loss	1.0000
15:89790948:CTCA:C	donor_gain	1.0000
15:89790949:TCA:T	donor_loss	1.0000
15:89790950:CACTC:C	donor_loss	1.0000
15:89790951:A:AC	donor_gain	1.0000
15:89790951:ACTCG:A	donor_loss	1.0000

AlphaMissense

6396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:89804266:T:A	E389V	1.000
15:89804270:G:C	H388D	1.000
15:89804368:T:A	E355V	1.000
15:89804370:C:A	M354I	1.000
15:89804370:C:G	M354I	1.000
15:89804370:C:T	M354I	1.000
15:89801550:A:G	W543R	0.999
15:89801550:A:T	W543R	0.999
15:89803647:C:A	K479N	0.999
15:89803647:C:G	K479N	0.999
15:89803668:A:C	F472L	0.999
15:89803668:A:T	F472L	0.999
15:89803670:A:G	F472L	0.999
15:89803949:C:A	E411D	0.999
15:89803949:C:G	E411D	0.999
15:89803950:T:A	E411V	0.999
15:89803960:A:G	W408R	0.999
15:89803960:A:T	W408R	0.999
15:89803970:C:A	W404C	0.999
15:89803970:C:G	W404C	0.999
15:89803972:A:G	W404R	0.999
15:89803972:A:T	W404R	0.999
15:89803995:C:A	G396V	0.999
15:89803995:C:T	G396E	0.999
15:89803996:C:A	G396W	0.999
15:89804002:A:G	W394R	0.999
15:89804002:A:T	W394R	0.999
15:89804256:G:C	H392Q	0.999
15:89804256:G:T	H392Q	0.999
15:89804258:G:C	H392D	0.999

dbSNP variants (sampled 300 via entrez): RS1000043327 (15:89795588 C>T), RS1000152961 (15:89808772 C>A,G,T), RS1000169670 (15:89791593 A>C,G), RS1000211512 (15:89793189 G>A), RS1000574488 (15:89789212 T>C), RS1000577907 (15:89809884 G>C), RS1000645948 (15:89787918 T>A,C), RS1000684992 (15:89794048 G>A), RS1000696489 (15:89810757 T>A), RS1000713398 (15:89810084 G>A,C), RS1000821360 (15:89798835 G>C), RS1000822585 (15:89804775 C>T), RS1001174189 (15:89789709 G>A), RS1001237693 (15:89793223 G>A), RS1001480535 (15:89800318 C>T)

Disease associations

OMIM: gene MIM:151530 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005580_34	Intraocular pressure	3.000000e-13
GCST005580_63	Intraocular pressure	4.000000e-12
GCST007209_15	Gallstone disease	6.000000e-11
GCST90011898_43	Alanine aminotransferase levels	2.000000e-10
GCST90013405_11	Liver enzyme levels (alanine transaminase)	4.000000e-22
GCST90013663_61	Alanine aminotransferase levels	6.000000e-18
GCST90013664_91	Aspartate aminotransferase levels	4.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1907 (SINGLE PROTEIN), CHEMBL3831223 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 268,863 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2103847	TOSEDOSTAT	2	328
CHEMBL29292	UBENIMEX	2	38,430
CHEMBL469912	PUROMYCIN	2	136,223

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M1: Aminopeptidase N

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
compound I3 [PMID: 23428964]	Inhibition	9.46	pKi
compound 1a [PMID: 25692029]	Inhibition	8.54	pKi
BTB07018	Inhibition	6.0	pKi
JFD00064	Inhibition	5.7	pKi
opiorphin	Inhibition	5.1	pIC50

ChEMBL bioactivities

314 potent at pChembl≥5 of 521 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	Ki	0.06	nM	CHEMBL1821980
9.80	Ki	0.16	nM	CHEMBL289824
9.68	Ki	0.21	nM	CHEMBL3355110
9.64	Ki	0.23	nM	CHEMBL3355099
9.46	Ki	0.35	nM	CHEMBL1852660
9.16	Ki	0.69	nM	CHEMBL3355109
9.10	Ki	0.79	nM	CHEMBL1090914
8.96	Ki	1.1	nM	CHEMBL3355111
8.89	Ki	1.3	nM	CHEMBL3355106
8.82	IC50	1.5	nM	CHEMBL4854733
8.81	IC50	1.549	nM	CHEMBL4854733
8.77	Ki	1.7	nM	CHEMBL3355104
8.70	Ki	2	nM	CHEMBL327844
8.68	Ki	2.1	nM	CHEMBL3355105
8.68	Ki	2.1	nM	CHEMBL3355108
8.66	Ki	2.2	nM	CHEMBL1235787
8.64	IC50	2.291	nM	CHEMBL4877339
8.64	IC50	2.3	nM	CHEMBL4877339
8.62	Ki	2.4	nM	CHEMBL3355101
8.58	Ki	2.62	nM	LEUCINE PHOSPHONIC ACID
8.54	Ki	2.9	nM	CHEMBL420321
8.44	IC50	3.631	nM	CHEMBL3416733
8.43	IC50	3.7	nM	CHEMBL3416733
8.35	Ki	4.5	nM	CHEMBL4460082
8.32	Ki	4.8	nM	CHEMBL117394
8.32	Ki	4.8	nM	CHEMBL3355100
8.14	Ki	7.2	nM	CHEMBL88808
8.10	Ki	8	nM	CHEMBL1159812
8.10	IC50	8	nM	CHEMBL448735
8.09	Ki	8.2	nM	CHEMBL4448936
8.07	IC50	8.6	nM	CHEMBL4853049
8.07	Ki	8.511	nM	CHEMBL1077583
8.06	IC50	8.71	nM	CHEMBL4853049
7.96	Ki	11	nM	CHEMBL1821978
7.96	Ki	11	nM	CHEMBL1160959
7.96	Ki	11	nM	CHEMBL3298942
7.96	Ki	11	nM	CHEMBL3298943
7.96	IC50	11	nM	CHEMBL1159812
7.90	Ki	12.59	nM	CHEMBL1077582
7.89	Ki	13	nM	CHEMBL3298944
7.72	Ki	19	nM	PROBESTIN
7.72	Ki	19	nM	CHEMBL4205440
7.72	Ki	19	nM	CHEMBL4217873
7.72	Ki	19.2	nM	CHEMBL4445188
7.70	Ki	20	nM	CHEMBL4210855
7.70	IC50	20	nM	CHEMBL4216928
7.70	IC50	20	nM	CHEMBL4208547
7.70	IC50	20	nM	CHEMBL1159809
7.70	IC50	20	nM	CHEMBL1159811
7.68	IC50	21	nM	CHEMBL1159810

PubChem BioAssay actives

309 with measured affinity, of 884 total; 50 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
7-amino-1-bromo-4-phenyl-5,7,8,9-tetrahydrobenzo[7]annulen-6-one;hydrochloride	1236837: Inhibition of human APN	ki	0.0001	uM
2-[[4-(aminomethyl)phenyl]methyl]-3-[(1-amino-3-pyridin-3-ylpropyl)-hydroxyphosphoryl]propanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0002	uM
(1-amino-3-phenylpropyl)-hydroxy-oxophosphanium	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0002	uM
[(1R)-1-amino-3-phenylpropyl]phosphonic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0002	uM
7-amino-1-bromo-4-phenyl-5,7,8,9-tetrahydrobenzo[7]annulen-6-one	738661: Inhibition of human APN using L-leucine-p-nitroanilide as substrate measured every 10 mins for 2 hrs by spectrophotometric analysis	ki	0.0003	uM
2-[[4-(aminomethyl)phenyl]methyl]-3-[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]propanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0007	uM
(1-amino-3-phenylpropyl)phosphonic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0008	uM
[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1765777: Inhibition of APN (unknown origin) using Ala-AMC as substrate	ic50	0.0010	uM
2-[[3-(aminomethyl)phenyl]methyl]-3-[(1-amino-3-pyridin-4-ylpropyl)-hydroxyphosphoryl]propanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0011	uM
2-[[(1-amino-3-pyridin-4-ylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0013	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid	1763043: Inhibition of APN (unknown origin) using A-AMC as substrate	ic50	0.0015	uM
2-[[[1-amino-3-[4-(hydroxymethyl)phenyl]propyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0017	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0020	uM
2-[[(1-amino-3-pyridin-3-ylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0021	uM
2-[[3-(aminomethyl)phenyl]methyl]-3-[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]propanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0021	uM
(2S)-2-[[(2S)-2-[[[(1R)-1-aminoethyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoyl]amino]-3-phenylpropanoic acid	689977: Inhibition of APN	ki	0.0022	uM
(2S)-2-[[(2S)-2-[[[(1R)-1-amino-3-phenylpropyl]-hydroxyphosphoryl]methyl]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1763043: Inhibition of APN (unknown origin) using A-AMC as substrate	ic50	0.0023	uM
2-[[[1-amino-3-(4-nitrophenyl)propyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0024	uM
[(1R)-1-amino-3-methylbutyl]phosphonic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0026	uM
(2S)-2-[[(2R)-2-[[[(1S)-1-aminoethyl]-hydroxyphosphoryl]methyl]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid	38380: Compound was evaluated for inhibition of enkephalin degrading enzyme, aminopeptidase N(APN)	ki	0.0029	uM
N-[2-(hydroxyamino)-2-oxo-1-[4-(3,4,5-trifluorophenyl)phenyl]ethyl]-4-(methanesulfonamido)benzamide	1607842: Inhibition of soluble human APN ectodomain stably expressed in HEK293 GnTI(-) cells using H-Leu-NHMec as substrate preincubated for 10 mins followed by substrate addition and measured for 1 hr by spectrofluorimetric method	ki	0.0045	uM
2-[[[1-amino-3-(3,5-dimethylphenyl)propyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0048	uM
(2S)-2-[[(2R)-2-[[[(S)-amino(phenyl)methyl]-hydroxyphosphoryl]methyl]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid	38380: Compound was evaluated for inhibition of enkephalin degrading enzyme, aminopeptidase N(APN)	ki	0.0048	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-3-(4-hydroxyphenyl)propanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0072	uM
(2S)-2-amino-4-methylpentane-1-thiol	2066912: Inhibition of FLAG-tagged human recombinant Aminopeptidase N	ic50	0.0080	uM
2-amino-4-methylsulfanylbutane-1-thiol	1380376: Inhibition of APN in human placenta using AlabetaNA as substrate	ki	0.0080	uM
N-[2-(hydroxyamino)-2-oxo-1-[4-(3,4,5-trifluorophenyl)phenyl]ethyl]-4-(sulfamoylamino)benzamide	1607842: Inhibition of soluble human APN ectodomain stably expressed in HEK293 GnTI(-) cells using H-Leu-NHMec as substrate preincubated for 10 mins followed by substrate addition and measured for 1 hr by spectrofluorimetric method	ki	0.0082	uM
(2S)-2-[[2-[(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-(aminomethyl)-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-oxo-1,4,5,10-tetrahydroazepino[3,4-b]indol-2-yl]acetyl]amino]-3-phenylpropanoic acid	468340: Inhibition of catalytic activity of human aminopeptidase N transfected in HEK293 cells assessed as formation of p-nitroaniline	ki	0.0085	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-[2-(1H-indol-3-yl)ethylcarbamoyl]-4-methylpentyl]phosphinic acid	1763043: Inhibition of APN (unknown origin) using A-AMC as substrate	ic50	0.0086	uM
(2S)-2-amino-4-methylsulfinylbutane-1-thiol;2,2,2-trifluoroacetic acid	1224571: Inhibition of human recombinant APN using L-Ala-beta-NA as substrate after 30 mins by fluorimetry	ki	0.0110	uM
(2S)-2-amino-4-methylsulfanylbutane-1-thiol;2,2,2-trifluoroacetic acid	1224571: Inhibition of human recombinant APN using L-Ala-beta-NA as substrate after 30 mins by fluorimetry	ki	0.0110	uM
benzyl 2-[[(2S)-2-[[[(2S)-2-amino-4-methylsulfanylbutyl]disulfanyl]methyl]-3-phenylpropanoyl]amino]-3-phenylpropanoate	38380: Compound was evaluated for inhibition of enkephalin degrading enzyme, aminopeptidase N(APN)	ki	0.0110	uM
7-amino-4-phenyl-5,7,8,9-tetrahydrobenzo[7]annulen-6-one;hydrochloride	738661: Inhibition of human APN using L-leucine-p-nitroanilide as substrate measured every 10 mins for 2 hrs by spectrophotometric analysis	ki	0.0110	uM
(2S)-2-[[2-[(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-(aminomethyl)-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-oxo-4,5-dihydro-1H-2-benzazepin-2-yl]acetyl]amino]-3-phenylpropanoic acid	468340: Inhibition of catalytic activity of human aminopeptidase N transfected in HEK293 cells assessed as formation of p-nitroaniline	ki	0.0126	uM
(2S)-2-aminohexane-1-thiol;2,2,2-trifluoroacetic acid	1224571: Inhibition of human recombinant APN using L-Ala-beta-NA as substrate after 30 mins by fluorimetry	ki	0.0130	uM
(2S)-1-[(2S)-1-[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid	753552: Inhibition of aminopeptidase N (unknown origin) using L-leucine-beta-naphthylamide as substrate after 15 mins	ki	0.0190	uM
(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R,3S)-3-amino-2-hydroxy-5-methylhexanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]butanedioic acid	1380363: Competitive inhibition of aminopeptidase-M (unknown origin)	ki	0.0190	uM
(2S)-1-[(2S)-1-[(2S)-2-[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxylic acid	1380363: Competitive inhibition of aminopeptidase-M (unknown origin)	ki	0.0190	uM
N-[2-(hydroxyamino)-2-oxo-1-[4-(3,4,5-trifluorophenyl)phenyl]ethyl]-1H-indazole-5-carboxamide	1607842: Inhibition of soluble human APN ectodomain stably expressed in HEK293 GnTI(-) cells using H-Leu-NHMec as substrate preincubated for 10 mins followed by substrate addition and measured for 1 hr by spectrofluorimetric method	ki	0.0192	uM
2-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethanamine	1380362: Inhibition of APN (unknown origin)	ic50	0.0200	uM
2-amino-2,4-dihydro-1H-phenanthren-3-one	1380390: Inhibition of aminopeptidase-M (unknown origin)	ki	0.0200	uM
2-amino-4-methylsulfinylbutane-1-thiol	1380362: Inhibition of APN (unknown origin)	ic50	0.0200	uM
2-amino-3-methylsulfanylpropane-1-thiol	1380362: Inhibition of APN (unknown origin)	ic50	0.0200	uM
(1-amino-3-methylbutyl)boronic acid	1380362: Inhibition of APN (unknown origin)	ic50	0.0200	uM
2-amino-3-methylsulfinylpropane-1-thiol	1380362: Inhibition of APN (unknown origin)	ic50	0.0210	uM
N-[2-(hydroxyamino)-2-oxo-1-[4-(3,4,5-trifluorophenyl)phenyl]ethyl]-2H-benzotriazole-5-carboxamide	1607842: Inhibition of soluble human APN ectodomain stably expressed in HEK293 GnTI(-) cells using H-Leu-NHMec as substrate preincubated for 10 mins followed by substrate addition and measured for 1 hr by spectrofluorimetric method	ki	0.0234	uM
2-[[[1-amino-3-(4-hydroxyphenyl)propyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0242	uM
3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-amine	1380362: Inhibition of APN (unknown origin)	ic50	0.0250	uM
(3S)-3-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-(aminomethyl)-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-phenylbutanoic acid	468340: Inhibition of catalytic activity of human aminopeptidase N transfected in HEK293 cells assessed as formation of p-nitroaniline	ki	0.0275	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-3-(3,5-dimethylphenyl)propanoic acid	1162777: Inhibition of human recombinant alanyl aminopeptidase after 30 to 60 mins by morrison’s equation	ki	0.0278	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Tetrachlorodibenzodioxin	increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation	4
Nickel	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
deoxynivalenol	decreases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
cobaltous chloride	affects expression, decreases expression	2
Decitabine	increases expression, increases reaction	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Smoke	decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
daidzein	affects cotreatment, affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
daidzin	affects cotreatment, affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
1,10-phenanthroline	decreases activity, increases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
periodate-oxidized adenosine	affects expression	1
cupric chloride	decreases expression	1

ChEMBL screening assays

109 unique, capped per target: 106 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1014281	Binding	Inhibition of aminopeptidase M at 10 uM	Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors. — Bioorg Med Chem Lett
CHEMBL4399454	ADMET	Drug metabolism in human plasma assessed as aminopeptidase N-mediated Tyr1-Gly2 cleavage by measuring half life	Applications of amide isosteres in medicinal chemistry. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1A1	Abcam THP-1 ANPEP KO	Cancer cell line	Male
CVCL_SC62	HAP1 ANPEP (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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