LAP3

Summary

LAP3 (leucine aminopeptidase 3, HGNC:18449) is a protein-coding gene on chromosome 4p15.32, encoding Cytosol aminopeptidase (P28838). Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides.

Predicted to enable peptidase activity. Predicted to be involved in proteolysis. Located in several cellular components, including extracellular exosome; focal adhesion; and mitochondrion.

Source: NCBI Gene 51056 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18449
Approved symbol	LAP3
Name	leucine aminopeptidase 3
Location	4p15.32
Locus type	gene with protein product
Status	Approved
Aliases	LAPEP, LAP
Ensembl gene	ENSG00000002549
Ensembl biotype	protein_coding
OMIM	170250
Entrez	51056

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000226299, ENST00000503467, ENST00000504614, ENST00000507960, ENST00000508014, ENST00000508497, ENST00000509583, ENST00000512397, ENST00000513105, ENST00000606142, ENST00000618908, ENST00000955710

RefSeq mRNA: 1 — MANE Select: NM_015907 NM_015907

CCDS: CCDS3422

Canonical transcript exons

ENST00000226299 — 13 exons

Exon	Start	End
ENSE00000706577	17582288	17582393
ENSE00000799252	17577198	17577567
ENSE00000799253	17607400	17607970
ENSE00003477633	17588819	17588977
ENSE00003490550	17604588	17604667
ENSE00003503602	17595410	17595534
ENSE00003560014	17598456	17598558
ENSE00003577766	17583483	17583642
ENSE00003591335	17581760	17581814
ENSE00003611157	17597046	17597134
ENSE00003630157	17579824	17579939
ENSE00003635787	17584972	17585136
ENSE00003677828	17606829	17606938

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 92.6194 / max 2866.5040, expressed in 1824 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47038	71.6572	1817
47037	12.4198	1794
47036	6.1052	1711
47039	1.4167	956
47034	0.5876	325
47033	0.2602	111
47035	0.1728	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.59	gold quality
monocyte	CL:0000576	98.54	gold quality
mononuclear cell	CL:0000842	98.44	gold quality
vermiform appendix	UBERON:0001154	98.42	gold quality
pericardium	UBERON:0002407	98.30	gold quality
leukocyte	CL:0000738	98.29	gold quality
jejunal mucosa	UBERON:0000399	98.26	gold quality
epithelium of nasopharynx	UBERON:0001951	98.26	gold quality
nasopharynx	UBERON:0001728	98.25	gold quality
parietal pleura	UBERON:0002400	98.04	gold quality
lymph node	UBERON:0000029	98.03	gold quality
pleura	UBERON:0000977	97.89	gold quality
superficial temporal artery	UBERON:0001614	97.82	gold quality
caecum	UBERON:0001153	97.69	gold quality
bronchial epithelial cell	CL:0002328	97.62	gold quality
visceral pleura	UBERON:0002401	97.60	gold quality
lower lobe of lung	UBERON:0008949	97.38	gold quality
heart right ventricle	UBERON:0002080	97.35	gold quality
decidua	UBERON:0002450	97.34	gold quality
eye	UBERON:0000970	97.25	gold quality
gall bladder	UBERON:0002110	97.23	gold quality
duodenum	UBERON:0002114	97.22	gold quality
jejunum	UBERON:0002115	97.19	gold quality
liver	UBERON:0002107	97.14	gold quality
adult mammalian kidney	UBERON:0000082	97.07	gold quality
nasal cavity epithelium	UBERON:0005384	97.05	gold quality
epithelium of bronchus	UBERON:0002031	96.90	gold quality
nasal cavity mucosa	UBERON:0001826	96.89	gold quality
adult organism	UBERON:0007023	96.89	gold quality
bronchus	UBERON:0002185	96.84	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	24.91
E-CURD-88	yes	19.45
E-MTAB-7037	no	316.19
E-MTAB-6142	no	309.99
E-MTAB-7052	no	252.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

38 targeting LAP3, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-5701	98.97	69.54	1502

Literature-anchored findings (GeneRIF, showing 8)

• results suggest that Lys528 is important for maximal activity of adipocyte-derived LAP by maintaining the appropriate structure of the substrate pocket of the enzyme (PMID:16513116)
• Overexpression of leucine aminopeptidase 3 contributes to malignant development of human esophageal squamous cell carcinoma. (PMID:24477662)
• our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of hepatocellular carcinoma (PMID:25120751)
• LAP3 might be a new prognostic factor and be close correlation with glioma cell growth, migration, invasion. (PMID:25453285)
• Leucine aminopeptidase 3 promotes migration and invasion of breast cancer cells through upregulation of fascin and matrix metalloproteinases-2/9 expression. (PMID:30417585)
• Urinary leucine aminopeptidase 3 in population environmentally exposed to airborne arsenic. (PMID:33501841)
• Proteomic Analysis of Hepatocellular Carcinoma Tissues With Encapsulation Shows Up-regulation of Leucine Aminopeptidase 3 and Phosphoenolpyruvate Carboxykinase 2. (PMID:33893083)
• Cholesterol-induced leucine aminopeptidase 3 (LAP3) upregulation inhibits cell autophagy in pathogenesis of NAFLD. (PMID:35404840)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	lap3	ENSDARG00000061981
mus_musculus	Lap3	ENSMUSG00000039682
rattus_norvegicus	Lap3	ENSRNOG00000003289
drosophila_melanogaster	S-Lap5	FBGN0033860
drosophila_melanogaster	S-Lap7	FBGN0033868
drosophila_melanogaster	S-Lap8	FBGN0034132
drosophila_melanogaster	S-Lap1	FBGN0035915
drosophila_melanogaster	S-Lap3	FBGN0045770
drosophila_melanogaster	S-Lap4	FBGN0052064
drosophila_melanogaster	S-Lap2	FBGN0052351
drosophila_melanogaster	loopin-1	FBGN0259795

Paralogs (1): NPEPL1 (ENSG00000215440)

Protein

Protein identifiers

Cytosol aminopeptidase — P28838 (reviewed: P28838)

Alternative names: Cysteinylglycine-S-conjugate dipeptidase, Leucine aminopeptidase 3, Leucyl aminopeptidase, Peptidase S, Proline aminopeptidase, Prolyl aminopeptidase

All UniProt accessions (2): P28838, H0Y9Q1

UniProt curated annotations — full annotation on UniProt →

Function. Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status.

Subunit / interactions. Homohexamer.

Subcellular location. Cytoplasm.

Cofactor. Binds two metal ions per subunit. Two metal binding sites with different affinities are located in the enzyme active site and can be occupied in vitro by different metals: site 1 is occupied by Zn(2+), Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be occupied by only Zn(2+) or Co(2+). One Zn(2+) ion is tightly bound to site 2 and essential for enzyme activity in vivo, while site 1 can be occupied by different metals to give different enzymatic activities. Mn(2+) is required for Cys-Gly hydrolysis activity. A third metal binding site may serve a structural role, possibly stabilizing part of the interface between the N-terminal and the catalytic domain.

Similarity. Belongs to the peptidase M17 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P28838-1	1	yes
P28838-2	2

RefSeq proteins (1): NP_056991* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000819	Peptidase_M17_C	Domain
IPR008283	Peptidase_M17_N	Domain
IPR011356	Leucine_aapep/pepB	Family
IPR023042	Peptidase_M17_leu_NH2_pept	Family
IPR043472	Macro_dom-like	Homologous_superfamily

Pfam: PF00883, PF02789

Enzyme classification (BRENDA):

• EC 3.4.11.1 — leucyl aminopeptidase (BRENDA: 101 organisms, 467 substrates, 423 inhibitors, 209 Km, 161 kcat entries)
• EC 3.4.11.2 — membrane alanyl aminopeptidase (BRENDA: 57 organisms, 398 substrates, 1043 inhibitors, 151 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
LEU-GLY	1.5–8.4	10
L-LEU-4-NITROANILIDE	0.035–12.7	9
LEU-4-NITROANILIDE	0.22–8.8	8
L-LEU-4-NITROANILIDE	0.17–9.23	8
L-LEU-7-AMIDO-4-METHYLCOUMARIN	0.012–1.38	7
L-ALA-4-NITROANILIDE	0.032–14	7
L-LEUCINE-4-METHYLCOUMARYL-7-AMIDE	0.015–0.35	6
LEUCYL-4-METHYLCOUMARYL-7-AMIDE	0.0131–0.173	6
ALA-2-NAPHTHYLAMIDE	0.038–1	6
BETA-CYCLOHEXYL-L-ALANYL-4-METHYLCOUMARYL-7-AMID	0.0011–0.539	5
LEU-P-NITROANILIDE	0.17–0.97	5
LEUCINAMIDE	4.02–17	5
L-ARG-2-NAPHTHYLAMIDE	0.025–0.099	5
LEU-2-NAPHTHYLAMIDE	0.02–0.095	5
L-ALANINE-4-METHYLCOUMARYL-7-AMIDE	0.054–1.16	4

Catalyzed reactions (Rhea), 3 shown:

• L-cysteinylglycine + H2O = L-cysteine + glycine (RHEA:28783)
• an S-substituted L-cysteinylglycine + H2O = an S-substituted L-cysteine + glycine (RHEA:60444)
• S-benzyl-L-cysteinylglycine + H2O = S-benzyl-L-cysteine + glycine (RHEA:62568)

UniProt features (42 total): binding site 20, modified residue 15, sequence conflict 3, active site 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28838-F1	94.18	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.

Catalytic / active sites (2): 294; 368

Ligand- & substrate-binding residues (20): 287; 287; 292; 294; 303; 305; 305; 364; 364; 364; 366; 366 …

Post-translational modifications (15): 42, 45, 54, 61, 103, 180, 194, 221, 221, 238, 455, 455, 476, 489, 489

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 293 (showing top): MODULE_172, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, KOINUMA_COLON_CANCER_MSI_UP, MODULE_317, MODULE_528, USF_C, WIELAND_UP_BY_HBV_INFECTION, GOCC_TRANS_GOLGI_NETWORK, ONKEN_UVEAL_MELANOMA_UP, MYCMAX_01, DAUER_STAT3_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (2): proteolysis (GO:0006508), protein metabolic process (GO:0019538)

GO Molecular Function (9): aminopeptidase activity (GO:0004177), carboxypeptidase activity (GO:0004180), peptidase activity (GO:0008233), metalloexopeptidase activity (GO:0008235), manganese ion binding (GO:0030145), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), trans-Golgi network (GO:0005802), focal adhesion (GO:0005925), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exopeptidase activity	3
intracellular membrane-bounded organelle	2
protein metabolic process	1
macromolecule metabolic process	1
primary metabolic process	1
hydrolase activity	1
catalytic activity, acting on a protein	1
metallopeptidase activity	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
Golgi apparatus subcompartment	1
cell-substrate junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

2018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAP3	XPNPEP1	Q9NQW7	956
LAP3	XPNPEP2	O43895	890
LAP3	CRYZL1	O95825	861
LAP3	UTP3	Q9NQZ2	818
LAP3	JCHAIN	P01591	766
LAP3	PGM2	Q96G03	719
LAP3	DNPEP	Q9ULA0	689
LAP3	RNPEP	Q9H4A4	686
LAP3	PIGR	P01833	651
LAP3	KLK4	Q9Y5K2	645
LAP3	ANPEP	P15144	631
LAP3	LCORL	Q8N3X6	613
LAP3	KNG1	P01042	600
LAP3	XPNPEP3	Q9NQH7	582
LAP3	NPEPPS	P55786	571

IntAct

76 interactions, top by confidence:

A	B	Type	Score
rep	LAP3	psi-mi:“MI:0915”(physical association)	0.620
MAPRE3	LAP3	psi-mi:“MI:0915”(physical association)	0.560
LAP3	BANP	psi-mi:“MI:0915”(physical association)	0.560
LAP3	ZYX	psi-mi:“MI:0915”(physical association)	0.560
LAP3	CBX3	psi-mi:“MI:0915”(physical association)	0.560
LAP3	CBX5	psi-mi:“MI:0915”(physical association)	0.560
LAP3	ZNF76	psi-mi:“MI:0915”(physical association)	0.560
LAP3	MAPRE3	psi-mi:“MI:0915”(physical association)	0.560
LAP3	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
LAP3	PIK3R3	psi-mi:“MI:0915”(physical association)	0.560
USF1	LAP3	psi-mi:“MI:0915”(physical association)	0.560
NDUFS5	NDUFS8	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
LAP3	PCNA	psi-mi:“MI:0915”(physical association)	0.370
TSG101	LAP3	psi-mi:“MI:0915”(physical association)	0.370
LAP3	FXR1	psi-mi:“MI:0915”(physical association)	0.370
LAP3	Trappc2	psi-mi:“MI:0915”(physical association)	0.370
LAP3	TRAPPC2L	psi-mi:“MI:0915”(physical association)	0.370
TAB1	LAP3	psi-mi:“MI:0915”(physical association)	0.370
LAP3	GCNT1	psi-mi:“MI:0915”(physical association)	0.370
LAP3	RAB7A	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PRKCE	PAPSS1	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.350
rep	ZNRD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (135): LAP3 (Affinity Capture-MS), LAP3 (Affinity Capture-MS), FUBP1 (Co-fractionation), MIF (Co-fractionation), PRDX1 (Co-fractionation), PRDX2 (Co-fractionation), TKT (Co-fractionation), VARS (Co-fractionation), LAP3 (Affinity Capture-MS), LAP3 (Synthetic Growth Defect), LAP3 (Affinity Capture-MS), RAB7A (Affinity Capture-MS), RBM39 (Affinity Capture-MS), ZCCHC17 (Affinity Capture-MS), LAP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2I2F2I5, A5A6L0, A7MB35, G0SHF3, O13366, O24457, P07342, P08559, P14874, P16387, P21839, P21953, P26267, P26268, P26284, P28838, P28839, P29803, P29804, P34385, P35486, P35487, P35738, P52899, P52900, P52901, P52902, P52903, Q06437, Q10489, Q2NL26, Q3ZC84, Q41768, Q41769, Q54C70, Q5R432, Q5R490, Q654V6, Q6K2E8, Q6P3A8

Diamond homologs: A0K9N9, A0KPF3, A1JJ31, A1K9L5, A1V5Z5, A2SAC2, A2SH61, A3MLR1, A3N1A7, A3N6U4, A3NSI1, A3QBG2, A4G7P5, A4JGZ2, A4SSA7, A4TQP6, A6T0V4, A6TWW9, A7FML9, A7NG41, A8G978, A8ML24, A9AHG9, A9IIK3, A9R5F5, B0BQ37, B1JLS9, B1JWV2, B1YUW5, B2J3G8, B2JET5, B2K3E9, B2T146, B2UAK8, B3ED46, B3GXY6, B3QNM5, B3QVE8, B3R663, B4E8G9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Tosedostat	down-regulates	LAP3	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2051 predictions. Top by Δscore:

Variant	Effect	Δscore
4:17577566:AGG:A	donor_loss	1.0000
4:17577567:GGTGA:G	donor_loss	1.0000
4:17579937:CAT:C	donor_gain	1.0000
4:17579937:CATGT:C	donor_loss	1.0000
4:17579938:AT:A	donor_gain	1.0000
4:17579938:ATG:A	donor_loss	1.0000
4:17579939:TGTAA:T	donor_loss	1.0000
4:17579940:G:A	donor_loss	1.0000
4:17579940:G:GG	donor_gain	1.0000
4:17579941:TA:T	donor_loss	1.0000
4:17579942:AAGT:A	donor_loss	1.0000
4:17583480:AAGC:A	acceptor_gain	1.0000
4:17583480:AAGCG:A	acceptor_gain	1.0000
4:17583481:A:G	acceptor_gain	1.0000
4:17583639:G:GT	donor_gain	1.0000
4:17583640:A:T	donor_gain	1.0000
4:17584970:A:AG	acceptor_gain	1.0000
4:17584970:AGTGG:A	acceptor_gain	1.0000
4:17584971:G:GG	acceptor_gain	1.0000
4:17584971:GTGGG:G	acceptor_gain	1.0000
4:17585113:T:TA	donor_gain	1.0000
4:17585114:A:AA	donor_gain	1.0000
4:17588810:A:AG	acceptor_gain	1.0000
4:17588811:C:G	acceptor_gain	1.0000
4:17588813:CTATA:C	acceptor_gain	1.0000
4:17588814:TATA:T	acceptor_loss	1.0000
4:17588814:TATAG:T	acceptor_gain	1.0000
4:17588815:A:AG	acceptor_gain	1.0000
4:17588815:ATAG:A	acceptor_loss	1.0000
4:17588815:ATAGA:A	acceptor_gain	1.0000

AlphaMissense

3407 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:17588970:T:C	F286L	1.000
4:17588972:T:A	F286L	1.000
4:17588972:T:G	F286L	1.000
4:17585031:G:C	R200P	0.999
4:17588959:A:T	K282I	0.999
4:17588962:G:A	G283E	0.999
4:17588974:A:T	D287V	0.999
4:17588975:C:A	D287E	0.999
4:17588975:C:G	D287E	0.999
4:17588976:A:C	S288R	0.999
4:17595410:T:A	S288R	0.999
4:17595410:T:G	S288R	0.999
4:17595412:G:A	G289D	0.999
4:17595412:G:T	G289V	0.999
4:17595415:G:A	G290D	0.999
4:17595428:G:C	K294N	0.999
4:17595428:G:T	K294N	0.999
4:17595452:G:A	M302I	0.999
4:17595452:G:C	M302I	0.999
4:17595452:G:T	M302I	0.999
4:17595460:A:T	D305V	0.999
4:17597068:T:A	N337K	0.999
4:17597068:T:G	N337K	0.999
4:17598471:G:C	A365P	0.999
4:17598477:G:A	G367R	0.999
4:17598477:G:C	G367R	0.999
4:17598477:G:T	G367W	0.999
4:17598546:G:C	A390P	0.999
4:17604603:C:A	A399D	0.999
4:17604623:G:T	G406W	0.999

dbSNP variants (sampled 300 via entrez): RS1000091363 (4:17576920 C>CA), RS1000134747 (4:17600025 C>T), RS1000145733 (4:17589058 G>A,C,T), RS1000177339 (4:17588761 T>C), RS10002358 (4:17604019 A>C,T), RS1000255196 (4:17594017 T>C,G), RS10003291 (4:17599105 A>C,G), RS1000352773 (4:17583587 T>C), RS1000533996 (4:17577334 G>A,C,T), RS10005380 (4:17591490 G>T), RS1000587800 (4:17595162 G>C), RS1000648586 (4:17577139 C>A,T), RS1000696720 (4:17594770 T>C), RS1000785962 (4:17583259 C>T), RS1000822036 (4:17583841 T>A)

Disease associations

OMIM: gene MIM:170250 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831223 (PROTEIN FAMILY), CHEMBL3965 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,758 (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
CHEMBL2103847	TOSEDOSTAT	2	328
CHEMBL29292	UBENIMEX	2	38,430

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M17: Leucyl aminopeptidase

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

Ligand	Action	Affinity	Parameter
bestatin	Inhibition	9.22	pKi

ChEMBL bioactivities

50 potent at pChembl≥5 of 73 total, top 48 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	UBENIMEX
9.22	Ki	0.6	nM	UBENIMEX
8.30	IC50	5	nM	TOSEDOSTAT
7.70	Ki	20	nM	UBENIMEX
7.52	Ki	30	nM	AMASTATIN
7.35	Ki	45	nM	CHEMBL254284
7.30	Ki	50	nM	CHEMBL4208547
7.22	Ki	60	nM	CHEMBL88476
7.19	Ki	65	nM	CHEMBL2153736
7.19	Ki	65	nM	CHEMBL328319
7.18	Ki	66	nM	CHEMBL327844
7.17	Ki	67	nM	CHEMBL88808
7.13	Ki	74	nM	CHEMBL327182
7.12	Ki	76	nM	CHEMBL284501
6.96	Ki	110	nM	CHEMBL328319
6.92	Ki	120	nM	CHEMBL1689155
6.75	IC50	180	nM	CHEMBL79092
6.70	Ki	200	nM	AMASTATIN
6.66	Ki	220	nM	AMASTATIN
6.64	Ki	230	nM	LEUCINE PHOSPHONIC ACID
6.64	Ki	230	nM	CHEMBL89318
6.64	Ki	230	nM	CHEMBL1093530
6.57	Ki	271	nM	CHEMBL252204
6.54	IC50	290	nM	CHEMBL78505
6.52	IC50	300	nM	CHEMBL311875
6.48	Ki	330	nM	CHEMBL68979
6.48	Ki	330	nM	CHEMBL88179
6.38	Ki	420	nM	CHEMBL40813
6.38	Ki	420	nM	CHEMBL1090913
6.38	Ki	420	nM	CHEMBL1093247
6.33	Ki	470	nM	CHEMBL38475
6.30	Ki	500	nM	CHEMBL134319
6.29	Ki	510	nM	CHEMBL309130
6.26	Ki	550	nM	CHEMBL305198
6.05	Ki	890	nM	CHEMBL3143143
6.00	Ki	1000	nM	CHEMBL40508
6.00	Ki	1000	nM	CHEMBL1204264
6.00	Ki	988	nM	CHEMBL393949
5.92	Ki	1200	nM	CHEMBL41544
5.91	Ki	1240	nM	CHEMBL134414
5.89	Ki	1300	nM	CHEMBL4213478
5.80	IC50	1600	nM	CHEMBL2369857
5.60	IC50	2500	nM	CHEMBL78699
5.44	Ki	3600	nM	CHEMBL289058
5.36	Ki	4400	nM	CHEMBL67868
5.31	Ki	4880	nM	CHEMBL423870
5.11	IC50	7800	nM	CHEMBL2369858
5.06	Ki	8800	nM	CHEMBL254285

PubChem BioAssay actives

50 with measured affinity, of 154 total; 43 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
(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid	2066914: Inhibition of human recombinant Leucine aminopeptidase 3	ic50	0.0005	uM
cyclopentyl (2S)-2-[[(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl]amino]-2-phenylacetate	2066914: Inhibition of human recombinant Leucine aminopeptidase 3	ic50	0.0050	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]butanedioic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.0300	uM
(2S)-2-[[[(1R)-1-amino-3-phenylpropyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	314597: Inhibition of pig kidney cytosolic leucine aminopeptidase	ki	0.0450	uM
2-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethanamine	1380389: Inhibition of LAP (unknown origin)	ki	0.0500	uM
2-amino-4-methylpentanal	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.0600	uM
2-[[[(1R)-1-amino-3-methylbutyl]-hydroxyphosphoryl]methyl]-4-methylpentanoic acid	689978: Inhibition of LAP	ki	0.0650	uM
2-[[(1-amino-3-methylbutyl)-hydroxyphosphoryl]methyl]-4-methylpentanoic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.0650	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.0660	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-3-(4-hydroxyphenyl)propanoic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.0670	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-4-methylpentanoic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.0740	uM
methyl (Z,5S)-5-amino-7-methyl-4-oxooct-2-enoate	101336: Inhibitory activity against leucine aminopeptidase	ki	0.0760	uM
(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl]amino]-4-methylpentanoic acid	101208: Compound was evaluated for the inhibition of Leucine aminopeptidase and the inhibition constant was determined after preincubating the enzyme and inhibitor	ki	0.1200	uM
(2S)-1-[(4R)-3-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-1,3-thiazolidine-4-carbonyl]-N-[(2S)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	101349: Inhibition against Leucyl aminopeptidase from pig kidney.	ic50	0.1800	uM
(1-amino-3-methylbutyl)phosphonic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.2300	uM
[(1R)-1-amino-3-methylbutyl]phosphonic acid	101210: Inhibition of Leucine aminopeptidase isolated from porcine kidney.	ki	0.2300	uM
(1-amino-3-methylbutyl)-phenoxyphosphinic acid	472440: Inhibition of leucine aminopeptidase	ki	0.2300	uM
(2R)-2-[[[(1R)-1-amino-3-phenylpropyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	314597: Inhibition of pig kidney cytosolic leucine aminopeptidase	ki	0.2710	uM
(2S)-1-[(2S)-1-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carbonyl]-N-[(2S)-1-[[(2S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	101349: Inhibition against Leucyl aminopeptidase from pig kidney.	ic50	0.2900	uM
(2S)-1-[(2S)-1-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carbonyl]-N-[(2S)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	101349: Inhibition against Leucyl aminopeptidase from pig kidney.	ic50	0.3000	uM
3-[(1-amino-3-methylbutyl)-hydroxyphosphoryl]propanoic acid	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	0.3300	uM
(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanethioyl]amino]-4-methylpentanoic acid;2,2,2-trifluoroacetic acid	101204: Inhibitory activity against Leucine aminopeptidase	ki	0.3300	uM
[(1R)-1-amino-2-phenylethyl]phosphonic acid	101210: Inhibition of Leucine aminopeptidase isolated from porcine kidney.	ki	0.4200	uM
(1-amino-2-phenylethyl)-phenoxyphosphinic acid	472440: Inhibition of leucine aminopeptidase	ki	0.4200	uM
(1-amino-2-phenylethyl)phosphonic acid	472440: Inhibition of leucine aminopeptidase	ki	0.4200	uM
1-aminooctylphosphonic acid	101211: Compound was tested for inhibition of Leucine aminopeptidase isolated from porcine kidney; Inhibitor exhibits slow-binding behavior(k on <=1000Me-1Se-1)	ki	0.4700	uM
(2R,3S)-3-amino-2-hydroxy-N-(3-methylbutyl)-4-phenylbutanamide	101209: Compound was evaluated for the inhibition of Leucine aminopeptidase from porcine kidney and the inhibition constant was determined after preincubating the enzyme and inhibitor	ki	0.5000	uM
(2S,3R)-3-amino-2-hydroxy-N-(3-methylbutyl)-4-phenylbutanamide	101204: Inhibitory activity against Leucine aminopeptidase	ki	0.5100	uM
(2S)-2-[[(2S,3R)-3-amino-4-phenyl-2-sulfanylbutanoyl]amino]-4-methylpentanoic acid	101204: Inhibitory activity against Leucine aminopeptidase	ki	0.5500	uM
(2R,3S)-3-amino-2-hydroxy-5-methyl-N-[(2S)-3-methyl-1-[[(2S)-3-methyl-1-(3-methylbutylamino)-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]hexanamide	101326: Compound was evaluated for the inhibition of Leucine aminopeptidase and the inhibition constant was determined after preincubating the enzyme and inhibitor	ki	0.8900	uM
(2S)-2-[[[(1S)-1-amino-3-phenylpropyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	314597: Inhibition of pig kidney cytosolic leucine aminopeptidase	ki	0.9880	uM
(2S)-2-[[(2S,3R)-3-amino-4-phenyl-2-sulfanylbutanoyl]amino]-4-methylpentanoic acid;hydrochloride	101204: Inhibitory activity against Leucine aminopeptidase	ki	1.0000	uM
1-aminohexylphosphonic acid	101210: Inhibition of Leucine aminopeptidase isolated from porcine kidney.	ki	1.0000	uM
(1-amino-2-methylpropyl)phosphonic acid	101211: Compound was tested for inhibition of Leucine aminopeptidase isolated from porcine kidney; Inhibitor exhibits slow-binding behavior(k on <=1000Me-1Se-1)	ki	1.2000	uM
2-[[2-[(3-amino-2-hydroxy-5-methylhexanoyl)amino]-3-methylbutanoyl]amino]butanedioic acid	101208: Compound was evaluated for the inhibition of Leucine aminopeptidase and the inhibition constant was determined after preincubating the enzyme and inhibitor	ki	1.2400	uM
3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-amine	1380389: Inhibition of LAP (unknown origin)	ki	1.3000	uM
(2S)-1-[(2S,4R)-1-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-N-[(2S)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	101349: Inhibition against Leucyl aminopeptidase from pig kidney.	ic50	1.6000	uM
(2S)-1-[(2S)-1-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide	101349: Inhibition against Leucyl aminopeptidase from pig kidney.	ic50	2.5000	uM
1-aminopropylphosphonic acid	101211: Compound was tested for inhibition of Leucine aminopeptidase isolated from porcine kidney; Inhibitor exhibits slow-binding behavior(k on <=1000Me-1Se-1)	ki	3.6000	uM
(2S,3R)-3-amino-2-hydroxy-N-(3-methylbutyl)-4-phenylbutanethioamide	101204: Inhibitory activity against Leucine aminopeptidase	ki	4.4000	uM
dilithium;2-[[(1-hydroxy-3-methylbutyl)-oxidophosphoryl]amino]acetate	101207: Binding affinity for cytosolic leucine aminopeptidase (LAP) from porcine kidney	ki	4.8800	uM
(2S)-1-[(2R,3S)-3-amino-2-hydroxy-5-methylhexanoyl]-N-[(2S)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide	101349: Inhibition against Leucyl aminopeptidase from pig kidney.	ic50	7.8000	uM
(2R)-2-[[[(1S)-1-amino-3-phenylpropyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	314597: Inhibition of pig kidney cytosolic leucine aminopeptidase	ki	8.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
bisphenol A	increases expression, increases methylation	2
Cadmium	increases abundance, increases expression	2
Nickel	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Furaldehyde	affects cotreatment, affects localization, decreases expression, increases expression	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

33 unique, capped per target: 32 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — J Nat Prod
CHEMBL1110138	Binding	Inhibition of proline iminopeptidase)	Inhibitors of prolyl oligopeptidases for the therapy of human diseases: defining diseases and inhibitors. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1G8	Abcam A-549 LAP3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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