RNPEP

Summary

RNPEP (arginyl aminopeptidase, HGNC:10078) is a protein-coding gene on chromosome 1q32.1, encoding Aminopeptidase B (Q9H4A4). Exopeptidase which selectively removes arginine and/or lysine residues from the N-terminus of several peptide substrates including Arg(0)-Leu-enkephalin, Arg(0)-Met-enkephalin and Arg(-1)-Lys(0)-somatostatin-14.

Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome.

Source: NCBI Gene 6051 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_020216

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10078
Approved symbol	RNPEP
Name	arginyl aminopeptidase
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	APB
Ensembl gene	ENSG00000176393
Ensembl biotype	protein_coding
OMIM	602675
Entrez	6051

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 14 protein_coding, 8 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000295640, ENST00000367286, ENST00000447312, ENST00000449524, ENST00000464707, ENST00000471105, ENST00000478617, ENST00000479531, ENST00000479726, ENST00000481780, ENST00000487116, ENST00000492587, ENST00000492849, ENST00000620670, ENST00000857425, ENST00000857426, ENST00000857427, ENST00000857428, ENST00000857429, ENST00000857430, ENST00000857431, ENST00000934089, ENST00000934090, ENST00000967255

RefSeq mRNA: 4 — MANE Select: NM_020216 NM_001319182, NM_001319183, NM_001319184, NM_020216

CCDS: CCDS1418

Canonical transcript exons

ENST00000295640 — 11 exons

Exon	Start	End
ENSE00001907903	201982648	201983113
ENSE00003472513	201988904	201989044
ENSE00003501987	202001376	202001488
ENSE00003514566	201997319	201997554
ENSE00003562736	202003237	202003461
ENSE00003662786	201996147	201996263
ENSE00003675663	201999902	202000015
ENSE00003679318	201989383	201989531
ENSE00003690248	202004354	202004496
ENSE00003790497	202001659	202001767
ENSE00003850180	202005558	202006143

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 97.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.9262 / max 223.1221, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7770	32.9907	1820
7772	2.4573	1158
7771	0.4782	264

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.32	gold quality
duodenum	UBERON:0002114	96.68	gold quality
granulocyte	CL:0000094	96.18	gold quality
rectum	UBERON:0001052	96.13	gold quality
monocyte	CL:0000576	96.10	gold quality
leukocyte	CL:0000738	96.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.03	gold quality
right uterine tube	UBERON:0001302	95.39	gold quality
esophagus mucosa	UBERON:0002469	95.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.04	gold quality
stromal cell of endometrium	CL:0002255	94.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.37	gold quality
small intestine	UBERON:0002108	94.31	gold quality
islet of Langerhans	UBERON:0000006	94.30	gold quality
transverse colon	UBERON:0001157	94.18	gold quality
right lobe of thyroid gland	UBERON:0001119	94.08	gold quality
blood	UBERON:0000178	94.03	gold quality
minor salivary gland	UBERON:0001830	93.98	gold quality
saliva-secreting gland	UBERON:0001044	93.91	gold quality
fallopian tube	UBERON:0003889	93.88	gold quality
left lobe of thyroid gland	UBERON:0001120	93.86	gold quality
thyroid gland	UBERON:0002046	93.85	gold quality
placenta	UBERON:0001987	93.81	gold quality
skin of abdomen	UBERON:0001416	93.78	gold quality
zone of skin	UBERON:0000014	93.67	gold quality
skin of leg	UBERON:0001511	93.61	gold quality
smooth muscle tissue	UBERON:0001135	93.54	gold quality
spleen	UBERON:0002106	93.52	gold quality
pancreas	UBERON:0001264	93.49	gold quality
ectocervix	UBERON:0012249	93.43	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	378.98
E-ANND-3	yes	13.02
E-MTAB-6911	no	220.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting RNPEP, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-4508	90.37	59.62	240
HSA-MIR-4781-5P	88.22	64.40	100

Literature-anchored findings (GeneRIF, showing 6)

• These data strongly suggest that the Asp 405 residue of aminopeptidase B is involved in substrate binding via an interaction with the P1 amino group of the substrate’s side chain. (PMID:16981702)
• Activities of aminopeptidases N and B and insulin-regulated aminopeptidase could be useful non-invasive biomarkers of Alzheimer’s disease from the earliest stages. (PMID:23500679)
• Data indicate that the importance of hydrogen bonds in aminopeptidase B (Ap-B) is verified by the Y229H substitution, which preserves the enzyme activity. (PMID:25530263)
• these results suggest a pathophysiological involvement of plasma peptidases and indicate that aminopeptidase activity can predict the course of first-episode psychosis patients, acting as a prognostic indicator (PMID:25997998)
• cytosolic peptidases(puromycin-sensitive aminopeptidase (PSA), aminopeptidase B (APB) and pyroglutamyl-peptidase I (PGI) ) may be involved in colorectal carcinogenesis (PMID:26078706)
• The substrate Angiotensin II, the enzymes aminopeptidases-A, B, M as well as IRAP were detected in the jejunal mucosa. (PMID:26311161)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnpep	ENSDARG00000012506
mus_musculus	Rnpep	ENSMUSG00000041926
rattus_norvegicus	Rnpep	ENSRNOG00000006720
drosophila_melanogaster	CG7653	FBGN0028935
drosophila_melanogaster	CG9806	FBGN0030222
drosophila_melanogaster	CG2111	FBGN0030223
drosophila_melanogaster	CG6071	FBGN0036186
drosophila_melanogaster	CG3502	FBGN0046253
drosophila_melanogaster	CG31445	FBGN0051445
drosophila_melanogaster	SP1029	FBGN0263236

Paralogs (11): TRHDE (ENSG00000072657), LTA4H (ENSG00000111144), LNPEP (ENSG00000113441), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), AOPEP (ENSG00000148120), ERAP1 (ENSG00000164307), ERAP2 (ENSG00000164308), ANPEP (ENSG00000166825), LVRN (ENSG00000172901)

Protein

Protein identifiers

Aminopeptidase B — Q9H4A4 (reviewed: Q9H4A4)

Alternative names: Arginine aminopeptidase, Arginyl aminopeptidase

All UniProt accessions (6): Q9H4A4, A0A087WU27, A0A087WUS4, A6NKB8, C9JMZ3, H7C2T3

UniProt curated annotations — full annotation on UniProt →

Function. Exopeptidase which selectively removes arginine and/or lysine residues from the N-terminus of several peptide substrates including Arg(0)-Leu-enkephalin, Arg(0)-Met-enkephalin and Arg(-1)-Lys(0)-somatostatin-14. Can hydrolyze leukotriene A4 (LTA-4) into leukotriene B4 (LTB-4).

Subcellular location. Secreted.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M1 family.

RefSeq proteins (4): NP_001306111, NP_001306112, NP_001306113, NP_064601* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001930	Peptidase_M1	Family
IPR014782	Peptidase_M1_dom	Domain
IPR015211	Peptidase_M1_C	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR034015	M1_LTA4H	Family
IPR038502	M1_LTA-4_hydro/amino_C_sf	Homologous_superfamily
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR045357	Aminopeptidase_N-like_N	Domain
IPR049980	LTA4H_cat	Domain

Pfam: PF01433, PF09127, PF17900

Enzyme classification (BRENDA):

• EC 3.4.11.6 — aminopeptidase B (BRENDA: 35 organisms, 222 substrates, 305 inhibitors, 95 Km, 61 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-ARG-2-NAPHTHYLAMIDE	—	22
L-LYS-2-NAPHTHYLAMIDE	0.0001–0.333	6
ARG-7-AMIDO-4-METHYLCOUMARIN	0.0159–0.603	5
L-ARG-7-AMIDO-4-METHYLCOUMARIN	0.048–0.208	5
L-ARG-BETA-NAPHTHYLAMIDE	0.0026–0.3	4
ARG-MET-ENKEPHALIN	0.021–0.125	3
L-ALA-ALA-PRO-LEU-4-NITROANILIDE	0.043–0.072	3
N-NAPHTHALEN-2-YL-L-ARGININAMIDE	0.1–0.2	3
ARG 4-METHYLCOUMARIN 7-AMIDE	0.0533–0.0774	2
ARG-BETA-NAPHTHYLAMIDE	0.183–0.267	2
ARGINYL-4-METHYLCOUMARIN 7-AMIDE	0.07–0.27	2
KALLIDIN	0.0157–0.0651	2
L-LYS-4-NITROANILIDE	0.0544–0.85	2
L-LYS-7-AMIDO-4-METHYLCOUMARIN	0.323–0.598	2
L-LYS-BETA-NAPHTHYLAMIDE	0.12–0.36	2

UniProt features (18 total): sequence conflict 6, binding site 4, modified residue 3, initiator methionine 1, chain 1, sequence variant 1, active site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4A4-F1	95.04	0.94

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): 326 (proton acceptor); 414 (transition state stabilizer)

Ligand- & substrate-binding residues (4): 298–302; 325; 329; 348

Post-translational modifications (3): 446, 2, 7

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MORF_HDAC2, MODULE_16, CEBALLOS_TARGETS_OF_TP53_AND_MYC_DN, MORF_BUB3, MORF_PRKDC, MORF_PAPSS1, GOBP_PROTEOLYSIS, MORF_CSNK2B, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_AMINOPEPTIDASE_ACTIVITY

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (9): aminopeptidase activity (GO:0004177), epoxide hydrolase activity (GO:0004301), metalloexopeptidase activity (GO:0008235), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exopeptidase activity	2
protein metabolic process	1
ether hydrolase activity	1
metallopeptidase activity	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

1350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNPEP	CAPN10	Q9HC96	763
RNPEP	DNPEP	Q9ULA0	756
RNPEP	LAP3	P28838	686
RNPEP	PGPEP1	Q9NXJ5	671
RNPEP	DPP3	Q9NY33	633
RNPEP	PREP	P48147	588
RNPEP	CPB1	P15086	552
RNPEP	NRDC	O43847	490
RNPEP	AGT	P01019	477
RNPEP	CPE	P16870	475
RNPEP	A0A3B3ITX9	A0A3B3ITX9	474
RNPEP	NAV1	Q8NEY1	443
RNPEP	CPPED1	Q9BRF8	436
RNPEP	REN	P00797	429
RNPEP	POC5	Q8NA72	429

IntAct

36 interactions, top by confidence:

A	B	Type	Score
SEPTIN2	SEPTIN6	psi-mi:“MI:0914”(association)	0.950
TPD52L1	TPD52L2	psi-mi:“MI:0914”(association)	0.530
	RNPEP	psi-mi:“MI:0915”(physical association)	0.400
RNPEP	UBA1	psi-mi:“MI:0915”(physical association)	0.400
RNPEP	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.370
CASP9	HPRT1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
YWHAH	BRAF	psi-mi:“MI:0914”(association)	0.350
GPR160	FUT7	psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
AZU1	UBA6	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
FPR1	NBAS	psi-mi:“MI:0914”(association)	0.350
FZD10	PDE2A	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
HAVCR2	LGALS8	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
MARS2	DDX39A	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
NXF5	LRP6	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
SNRNP27	BPNT1	psi-mi:“MI:0914”(association)	0.350
TTC9C		psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
OCA2	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): RNPEP (Co-fractionation), RNPEP (Co-fractionation), RNPEP (Co-fractionation), RNPEP (Co-fractionation), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-RNA), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-RNA), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-MS), RNPEP (Affinity Capture-MS)

ESM2 similar proteins: A2ADA5, A4PCD4, A6H611, D3ZDM7, F6PHZ6, O75344, P04053, P09838, P17256, P36195, P47823, P55345, Q01992, Q03426, Q08602, Q0V8R7, Q13144, Q1L8I0, Q3MIT2, Q4KM92, Q4QQT0, Q5CZL1, Q5E9Z1, Q5I0L3, Q5M7T9, Q5M934, Q5RFE6, Q5XGM5, Q64350, Q6GQ53, Q7L3T8, Q80W22, Q86YJ6, Q8BYL4, Q8C0D0, Q8CHW4, Q8N0Z8, Q8WWH5, Q91XW8, Q92089

Diamond homologs: A1CSI2, A1DG68, A2QKF8, A3LQI7, A3LRX6, A4QUC1, A5DGF3, A5DME6, A5DSS4, A6QPT7, A6RCT2, A6SAG8, A6ZS33, A7EJL9, A7THG7, G5E872, G5EFT4, O09175, O94544, P09960, P19602, P24527, P30349, P52922, Q0CFY9, Q0U653, Q10736, Q10740, Q1DVD1, Q2GY21, Q2TZ99, Q3SZH7, Q4X265, Q59NB8, Q5B0W8, Q6BW21, Q6C3E5, Q6CLD3, Q6FTM0, Q6IP81

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1881 predictions. Top by Δscore:

Variant	Effect	Δscore
1:201988900:TTA:T	acceptor_loss	1.0000
1:201988901:TAG:T	acceptor_loss	1.0000
1:201988902:A:AG	acceptor_gain	1.0000
1:201988902:A:AT	acceptor_loss	1.0000
1:201988903:G:GG	acceptor_gain	1.0000
1:201988903:GGTTT:G	acceptor_gain	1.0000
1:201989046:T:G	donor_loss	1.0000
1:201990248:C:G	acceptor_gain	1.0000
1:201996231:A:T	donor_gain	1.0000
1:201996245:GACCT:G	donor_gain	1.0000
1:201996260:G:GT	donor_gain	1.0000
1:201996260:G:T	donor_gain	1.0000
1:201996261:A:T	donor_gain	1.0000
1:201997550:CTTTG:C	donor_loss	1.0000
1:201997552:TTGG:T	donor_loss	1.0000
1:201997553:TGGTA:T	donor_loss	1.0000
1:201997554:GGTAA:G	donor_loss	1.0000
1:201997555:G:C	donor_loss	1.0000
1:201997556:T:G	donor_loss	1.0000
1:202000022:G:GT	donor_gain	1.0000
1:202000025:GCTCC:G	donor_gain	1.0000
1:202001654:CACA:C	acceptor_loss	1.0000
1:202001656:CAGGC:C	acceptor_loss	1.0000
1:202001657:A:AG	acceptor_gain	1.0000
1:202001657:A:C	acceptor_loss	1.0000
1:202001658:G:GA	acceptor_gain	1.0000
1:202001658:GGC:G	acceptor_gain	1.0000
1:202001658:GGCCT:G	acceptor_gain	1.0000
1:202001764:CCAGG:C	donor_loss	1.0000
1:202001766:AGGTA:A	donor_loss	1.0000

AlphaMissense

4235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:201997347:T:C	F295L	0.999
1:201997349:T:A	F295L	0.999
1:201997349:T:G	F295L	0.999
1:201997366:A:T	E301V	0.999
1:201997437:C:G	H325D	0.999
1:201997441:A:T	E326V	0.999
1:201997449:C:G	H329D	0.999
1:201997455:T:A	W331R	0.999
1:201997455:T:C	W331R	0.999
1:201997462:G:A	G333E	0.999
1:201997462:G:T	G333V	0.999
1:201997466:C:A	N334K	0.999
1:201997466:C:G	N334K	0.999
1:201997471:T:A	V336D	0.999
1:201997485:T:A	W341R	0.999
1:201997485:T:C	W341R	0.999
1:201997497:T:A	W345R	0.999
1:201997497:T:C	W345R	0.999
1:201997507:A:T	E348V	0.999
1:201997508:A:C	E348D	0.999
1:201997508:A:T	E348D	0.999
1:201997509:G:C	G349R	0.999
1:202001411:T:C	Y414H	0.999
1:201989004:A:T	D183V	0.998
1:201997367:G:C	E301D	0.998
1:201997367:G:T	E301D	0.998
1:201997449:C:A	H329N	0.998
1:201997451:C:A	H329Q	0.998
1:201997451:C:G	H329Q	0.998
1:201997452:A:C	S330R	0.998

dbSNP variants (sampled 300 via entrez): RS1000006128 (1:201985937 T>G), RS1000010165 (1:201993168 C>T), RS1000034499 (1:201986240 T>G), RS1000081625 (1:201997819 A>G), RS1000086986 (1:201992826 C>T), RS1000191631 (1:202002151 C>A), RS1000608818 (1:201984434 G>C), RS1000611168 (1:201991103 C>T), RS1000661346 (1:201982691 G>A,C), RS1000818649 (1:201982563 A>C,G,T), RS1000929300 (1:202005876 C>G), RS1001007555 (1:201985162 C>T), RS1001009912 (1:201994410 A>T), RS1001083750 (1:201994076 C>A,T), RS1001221638 (1:201985848 A>G)

Disease associations

OMIM: gene MIM:602675 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001207_1	Butyrylcholinesterase levels	9.000000e-16
GCST003263_104	Post bronchodilator FEV1 in COPD	2.000000e-06
GCST003265_317	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST006585_2313	Blood protein levels	4.000000e-42
GCST009733_111	Urinary metabolite levels in chronic kidney disease	1.000000e-56

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004571	butyrylcholinesterase measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0005116	urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2432 (SINGLE PROTEIN), CHEMBL3831223 (PROTEIN FAMILY)

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
Lys-thiol	Inhibition	9.05	pKi

ChEMBL bioactivities

12 potent at pChembl≥5 of 13 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.05	Ki	0.9	nM	CHEMBL432852
7.96	Ki	11	nM	CHEMBL27163
7.38	Kd	41.75	nM	CHEMBL5653589
7.38	ED50	41.75	nM	CHEMBL5653589
7.29	Ki	51	nM	CHEMBL27010
6.77	Ki	170	nM	CHEMBL140459
6.18	Kd	664.1	nM	CHEMBL3752910
6.18	ED50	664.1	nM	CHEMBL3752910
5.82	Ki	1500	nM	CHEMBL143589
5.50	Ki	3200	nM	CHEMBL140846
5.46	IC50	3500	nM	CHEMBL3251698
5.19	Ki	6500	nM	CHEMBL140779

PubChem BioAssay actives

10 with measured affinity, of 18 total; 10 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
6-amino-2-sulfanylhexanoic acid	38916: Inhibition of arginylaminopeptidase (aminopeptidase B)	ki	0.0009	uM
4-methylsulfanyl-2-sulfanylbutanoic acid	38916: Inhibition of arginylaminopeptidase (aminopeptidase B)	ki	0.0110	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149233: Binding affinity to human RNPEP incubated for 45 mins by Kinobead based pull down assay	kd	0.0418	uM
4-methyl-2-sulfanylpentanoic acid	38916: Inhibition of arginylaminopeptidase (aminopeptidase B)	ki	0.0510	uM
(5S)-5-amino-2-benzyl-7-methyl-4-oxooctanoic acid	38917: Compound was tested for binding affinity towards arginyl aminopeptidase	ki	0.1700	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149233: Binding affinity to human RNPEP incubated for 45 mins by Kinobead based pull down assay	kd	0.6641	uM
3-amino-N-(3-methylbutyl)-2-oxo-4-phenylbutanamide	38917: Compound was tested for binding affinity towards arginyl aminopeptidase	ki	1.5000	uM
(3S)-3-amino-5-methyl-N-(3-methylbutyl)-2-oxohexanamide	38917: Compound was tested for binding affinity towards arginyl aminopeptidase	ki	3.2000	uM
(2S)-2-[[(2S,3R)-3-amino-4-cyclohexyl-2-hydroxybutanoyl]amino]-4-methylpentanoic acid	1303022: Inhibition of aminopeptidase B (unknown origin)	ic50	3.5000	uM
(3R)-3-amino-5-methyl-N-(3-methylbutyl)-2-oxohexanamide	38917: Compound was tested for binding affinity towards arginyl aminopeptidase	ki	6.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
sodium arsenite	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3812617	Binding	Inhibition of aminopeptidase B (unknown origin)	Stacking with No Planarity? — ACS Med Chem Lett
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

Clinical trials (associated diseases)

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