NPEPL1

Summary

NPEPL1 (aminopeptidase like 1, HGNC:16244) is a protein-coding gene on chromosome 20q13.32, encoding Probable aminopeptidase NPEPL1 (Q8NDH3). Probably catalyzes the removal of unsubstituted N-terminal amino acids from various peptides.

Predicted to enable peptidase activity. Predicted to be involved in proteolysis. Located in nucleus.

Source: NCBI Gene 79716 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total
• Druggable target: yes
• MANE Select transcript: NM_024663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16244
Approved symbol	NPEPL1
Name	aminopeptidase like 1
Location	20q13.32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11583, bA261P9.2
Ensembl gene	ENSG00000215440
Ensembl biotype	protein_coding
Entrez	79716

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000356091, ENST00000525068, ENST00000525817, ENST00000525967, ENST00000527081, ENST00000527587, ENST00000529976, ENST00000532531, ENST00000533788, ENST00000908534, ENST00000908535, ENST00000908536

RefSeq mRNA: 3 — MANE Select: NM_024663 NM_001204872, NM_001204873, NM_024663

CCDS: CCDS46621, CCDS56200, CCDS56201

Canonical transcript exons

ENST00000356091 — 12 exons

Exon	Start	End
ENSE00001408052	58692800	58693050
ENSE00003472199	58713420	58713543
ENSE00003490385	58713917	58714093
ENSE00003499580	58714560	58714670
ENSE00003516941	58712479	58712579
ENSE00003519326	58701016	58701158
ENSE00003587261	58715168	58715844
ENSE00003631109	58707123	58707200
ENSE00003633921	58693737	58693922
ENSE00003658484	58698684	58698773
ENSE00003677263	58699197	58699278
ENSE00003688992	58694422	58694592

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9059 / max 112.6543, expressed in 1667 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185516	6.5004	1531
185515	4.8079	1565
185517	0.3910	149
185514	0.1125	58
209176	0.0941	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.06	silver quality
mucosa of stomach	UBERON:0001199	96.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.81	gold quality
metanephros cortex	UBERON:0010533	95.77	gold quality
apex of heart	UBERON:0002098	95.63	gold quality
granulocyte	CL:0000094	95.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.54	gold quality
lower esophagus	UBERON:0013473	95.53	gold quality
cerebellar hemisphere	UBERON:0002245	95.41	gold quality
left lobe of thyroid gland	UBERON:0001120	95.38	gold quality
cerebellar cortex	UBERON:0002129	95.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.30	gold quality
cerebellum	UBERON:0002037	95.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.14	gold quality
right lobe of thyroid gland	UBERON:0001119	95.10	gold quality
fundus of stomach	UBERON:0001160	94.99	gold quality
spleen	UBERON:0002106	94.92	gold quality
thyroid gland	UBERON:0002046	94.78	gold quality
tibial nerve	UBERON:0001323	94.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.58	gold quality
minor salivary gland	UBERON:0001830	94.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.22	gold quality
right uterine tube	UBERON:0001302	94.20	gold quality
pituitary gland	UBERON:0000007	94.18	gold quality
blood	UBERON:0000178	94.06	gold quality
saliva-secreting gland	UBERON:0001044	94.05	gold quality
gastrocnemius	UBERON:0001388	93.97	gold quality
right coronary artery	UBERON:0001625	93.95	gold quality
adipose tissue	UBERON:0001013	93.85	gold quality
right lung	UBERON:0002167	93.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting NPEPL1, 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-4500	99.99	72.72	2367
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4505	99.27	67.81	2678

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	npepl1	ENSDARG00000012871
mus_musculus	Npepl1	ENSMUSG00000039263
rattus_norvegicus	Npepl1	ENSRNOG00000028384
drosophila_melanogaster	grsm	FBGN0040493
caenorhabditis_elegans		WBGENE00002249

Paralogs (1): LAP3 (ENSG00000002549)

Protein

Protein identifiers

Probable aminopeptidase NPEPL1 — Q8NDH3 (reviewed: Q8NDH3)

Alternative names: Aminopeptidase-like 1

All UniProt accessions (2): Q8NDH3, H0YEP3

UniProt curated annotations — full annotation on UniProt →

Function. Probably catalyzes the removal of unsubstituted N-terminal amino acids from various peptides.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the peptidase M17 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NDH3-1	1	yes
Q8NDH3-2	2
Q8NDH3-3	3
Q8NDH3-4	4
Q8NDH3-5	5

RefSeq proteins (3): NP_001191801, NP_001191802, NP_078939* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000819	Peptidase_M17_C	Domain
IPR011356	Leucine_aapep/pepB	Family
IPR041417	NPEPL1_N	Domain

Pfam: PF00883, PF18295

UniProt features (23 total): binding site 7, splice variant 6, sequence conflict 5, active site 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDH3-F1	94.16	0.91

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): 272; 346

Ligand- & substrate-binding residues (7): 260; 265; 265; 283; 342; 344; 344

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, AAGCAAT_MIR137, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_205, MARTINEZ_RB1_TARGETS_DN, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, TTTGCAC_MIR19A_MIR19B, GOBP_PROTEOLYSIS, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_AMINOPEPTIDASE_ACTIVITY, GOMF_MANGANESE_ION_BINDING, GOMF_EXOPEPTIDASE_ACTIVITY, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON

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

GO Molecular Function (7): peptidase activity (GO:0008233), manganese ion binding (GO:0030145), metalloaminopeptidase activity (GO:0070006), aminopeptidase activity (GO:0004177), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
macromolecule metabolic process	1
primary metabolic process	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
exopeptidase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPEPL1	STX16	O14662	627
NPEPL1	OR5B2	Q96R09	582
NPEPL1	CIMIP1	Q9H1P6	494
NPEPL1	RNF145	Q96MT1	465
NPEPL1	MRPS33	Q9Y291	458
NPEPL1	NCOA5	Q9HCD5	448
NPEPL1	SHISA4	Q96DD7	436
NPEPL1	USP39	Q53GS9	430
NPEPL1	ZSCAN26	Q16670	424
NPEPL1	PRPF19	Q9UMS4	423
NPEPL1	RIPOR1	Q6ZS17	417
NPEPL1	DNPEP	Q9ULA0	414
NPEPL1	DDX27	Q96GQ7	413
NPEPL1	VAPB	O95292	407
NPEPL1	IMPDH1	P20839	405

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NPEPL1	TFRC	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (44): NPEPL1 (Two-hybrid), HMBS (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation), NPEPL1 (Co-fractionation)

ESM2 similar proteins: A1AJG3, A4WF25, A5F5D8, A7ZVE0, A8A816, A9MET9, A9N680, B1ISB1, B4T3M4, B4TG58, B4TTA0, B5BKS6, B5F465, B5FSH0, B5R1K2, B5R9L5, B5Z3L7, B6I2H3, B7LCX0, B7M9L9, B7NGJ2, B7NUH4, B7UQR7, B8GTX6, C0Q7D6, C3LR42, C4LA51, P00727, P0C6E1, P28838, P28839, P30184, P68767, P68768, Q0SXK0, Q15PX4, Q1R2Z4, Q31TK2, Q328S1, Q3YU89

Diamond homologs: A0RKB5, A1BGN2, A1K9L5, A1KKQ5, A1UIA8, A3Q1S2, A4ISE0, A5CRI6, A5CXK2, A5G9C7, A5U4P1, A5VPM3, A6TWW9, A6X259, A7GUC8, A7Z8B5, A8EXL1, A8F0Q0, A8FH04, A8GQW7, A8GXC3, A8LI79, A8ML24, A9VMY8, B0BWB2, B0JL23, B1VZN5, B1YKV4, B2J3G8, B2UAK8, B2UTQ8, B2V6F5, B3ED46, B3QNM5, B3QVE8, B3R0N4, B5Z6U1, B6JLF2, B7HBG1, B7HUR5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3260 predictions. Top by Δscore:

Variant	Effect	Δscore
20:58693048:G:GT	donor_gain	1.0000
20:58693729:T:A	acceptor_gain	1.0000
20:58693729:T:TA	acceptor_gain	1.0000
20:58693736:GCTCT:G	acceptor_gain	1.0000
20:58693920:GTG:G	donor_gain	1.0000
20:58693923:G:GG	donor_gain	1.0000
20:58693923:GTG:G	donor_loss	1.0000
20:58694419:CAGA:C	acceptor_loss	1.0000
20:58694420:A:AG	acceptor_gain	1.0000
20:58694420:A:T	acceptor_loss	1.0000
20:58694420:AGAT:A	acceptor_gain	1.0000
20:58694421:G:GG	acceptor_gain	1.0000
20:58694421:GAT:G	acceptor_gain	1.0000
20:58694421:GATG:G	acceptor_gain	1.0000
20:58694593:G:C	donor_loss	1.0000
20:58694593:GTGG:G	donor_loss	1.0000
20:58694594:T:A	donor_loss	1.0000
20:58698682:A:AG	acceptor_gain	1.0000
20:58698683:G:GG	acceptor_gain	1.0000
20:58698683:GT:G	acceptor_gain	1.0000
20:58698683:GTGC:G	acceptor_gain	1.0000
20:58698770:CGAGG:C	donor_loss	1.0000
20:58698771:GAGG:G	donor_loss	1.0000
20:58698772:AG:A	donor_loss	1.0000
20:58698773:GG:G	donor_loss	1.0000
20:58698774:G:GA	donor_loss	1.0000
20:58699183:A:AG	acceptor_gain	1.0000
20:58699183:AT:A	acceptor_gain	1.0000
20:58699184:T:G	acceptor_gain	1.0000
20:58699184:T:TA	acceptor_gain	1.0000

AlphaMissense

3373 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:58701115:A:T	K260I	1.000
20:58701130:A:C	D265A	1.000
20:58701130:A:T	D265V	1.000
20:58701152:A:C	K272N	1.000
20:58701152:A:T	K272N	1.000
20:58713451:G:C	G345R	1.000
20:58714084:C:A	N431K	1.000
20:58714084:C:G	N431K	1.000
20:58701129:G:C	D265H	0.999
20:58701130:A:G	D265G	0.999
20:58701131:C:A	D265E	0.999
20:58701131:C:G	D265E	0.999
20:58701150:A:G	K272E	0.999
20:58701151:A:T	K272I	0.999
20:58707139:T:C	M280T	0.999
20:58707140:G:A	M280I	0.999
20:58707140:G:C	M280I	0.999
20:58707140:G:T	M280I	0.999
20:58707148:A:C	D283A	0.999
20:58707148:A:T	D283V	0.999
20:58707149:C:A	D283E	0.999
20:58707149:C:G	D283E	0.999
20:58712523:C:A	N315K	0.999
20:58712523:C:G	N315K	0.999
20:58713438:C:A	N340K	0.999
20:58713438:C:G	N340K	0.999
20:58713442:G:C	D342H	0.999
20:58713443:A:T	D342V	0.999
20:58713445:G:C	A343P	0.999
20:58713451:G:T	G345C	0.999

dbSNP variants (sampled 300 via entrez): RS1000017218 (20:58706305 A>C), RS1000070412 (20:58711476 G>T), RS1000261647 (20:58701640 C>T), RS1000311914 (20:58701612 G>A), RS1000476992 (20:58701815 C>T), RS1000488009 (20:58696244 C>T), RS1000514748 (20:58714901 G>A), RS1000526645 (20:58711288 C>T), RS1000547111 (20:58694627 C>G,T), RS1000568541 (20:58714727 C>A,T), RS1000580547 (20:58701783 G>A,T), RS1000745974 (20:58694870 C>A,T), RS1000865247 (20:58700043 C>G), RS1000939249 (20:58715101 G>A,C,T), RS1000970167 (20:58705146 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003264_1033	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_1610	Post bronchodilator FEV1/FVC ratio	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831223 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M17: Leucyl aminopeptidase

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
bisphenol A	decreases expression, increases expression	2
Particulate Matter	decreases reaction, increases expression, affects cotreatment, increases abundance	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
beta-lapachone	increases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
avobenzone	decreases expression	1
azoxystrobin	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
MT19c compound	decreases 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	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	decreases reaction, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Disulfiram	affects binding, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 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

Clinical trials (associated diseases)

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