DNPEP
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Also known as DAPASPEP
Summary
DNPEP (aspartyl aminopeptidase, HGNC:2981) is a protein-coding gene on chromosome 2q35, encoding Aspartyl aminopeptidase (Q9ULA0). Aminopeptidase with specificity towards an acidic amino acid at the N-terminus.
The protein encoded by this gene is an aminopeptidase which prefers acidic amino acids, and specifically favors aspartic acid over glutamic acid. It is thought to be a cytosolic protein involved in general metabolism of intracellular proteins. Several transcript variants encoding different isoforms have been found for this gene.
Source: NCBI Gene 23549 — RefSeq curated summary.
At a glance
- GWAS associations: 4
- Clinical variants (ClinVar): 99 total
- Druggable target: yes
- MANE Select transcript:
NM_012100
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:2981 |
| Approved symbol | DNPEP |
| Name | aspartyl aminopeptidase |
| Location | 2q35 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | DAP, ASPEP |
| Ensembl gene | ENSG00000123992 |
| Ensembl biotype | protein_coding |
| OMIM | 611367 |
| Entrez | 23549 |
Gene structure
Transcript identifiers
Ensembl transcripts: 30 — 20 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined
ENST00000273075, ENST00000322176, ENST00000373963, ENST00000373966, ENST00000373972, ENST00000429013, ENST00000430206, ENST00000434339, ENST00000457935, ENST00000460963, ENST00000462779, ENST00000488051, ENST00000488881, ENST00000490371, ENST00000519698, ENST00000519905, ENST00000520694, ENST00000521459, ENST00000522421, ENST00000523282, ENST00000523527, ENST00000851982, ENST00000851983, ENST00000851984, ENST00000851985, ENST00000851986, ENST00000925428, ENST00000964369, ENST00000964370, ENST00000964371
RefSeq mRNA: 8 — MANE Select: NM_012100
NM_001319116, NM_001319117, NM_001319118, NM_001319119, NM_001319120, NM_001319121, NM_001319122, NM_012100
CCDS: CCDS42823, CCDS82574, CCDS86923
Canonical transcript exons
ENST00000273075 — 15 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001224311 | 219387759 | 219387912 |
| ENSE00001771788 | 219372043 | 219374342 |
| ENSE00003460921 | 219385968 | 219386098 |
| ENSE00003479336 | 219381979 | 219382139 |
| ENSE00003489559 | 219385424 | 219385531 |
| ENSE00003494903 | 219386665 | 219386778 |
| ENSE00003508066 | 219385631 | 219385706 |
| ENSE00003511866 | 219381545 | 219381584 |
| ENSE00003527259 | 219386286 | 219386411 |
| ENSE00003570789 | 219387070 | 219387163 |
| ENSE00003579022 | 219386892 | 219386980 |
| ENSE00003585229 | 219374855 | 219375022 |
| ENSE00003594018 | 219384366 | 219384443 |
| ENSE00003651325 | 219381335 | 219381436 |
| ENSE00003667122 | 219383131 | 219383214 |
Expression profiles
Bgee: expression breadth ubiquitous, 295 present calls, max score 97.92.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7917 / max 114.2033, expressed in 1808 samples.
FANTOM5 promoters (6 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 34078 | 11.4917 | 1793 |
| 34076 | 6.0231 | 1666 |
| 34077 | 1.6437 | 1209 |
| 34074 | 0.3943 | 197 |
| 34075 | 0.2314 | 113 |
| 34079 | 0.0075 | 3 |
Top tissues by expression
299 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| left testis | UBERON:0004533 | 97.92 | gold quality |
| right testis | UBERON:0004534 | 97.90 | gold quality |
| endocervix | UBERON:0000458 | 97.57 | gold quality |
| mucosa of stomach | UBERON:0001199 | 97.49 | gold quality |
| apex of heart | UBERON:0002098 | 97.30 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 97.18 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 97.03 | gold quality |
| right ovary | UBERON:0002118 | 96.93 | gold quality |
| left uterine tube | UBERON:0001303 | 96.91 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 96.90 | gold quality |
| ectocervix | UBERON:0012249 | 96.87 | gold quality |
| transverse colon | UBERON:0001157 | 96.86 | gold quality |
| left ovary | UBERON:0002119 | 96.78 | gold quality |
| skin of leg | UBERON:0001511 | 96.70 | gold quality |
| body of uterus | UBERON:0009853 | 96.69 | gold quality |
| skin of abdomen | UBERON:0001416 | 96.61 | gold quality |
| small intestine | UBERON:0002108 | 96.54 | gold quality |
| gastrocnemius | UBERON:0001388 | 96.51 | gold quality |
| right lung | UBERON:0002167 | 96.40 | gold quality |
| omental fat pad | UBERON:0010414 | 96.37 | gold quality |
| body of stomach | UBERON:0001161 | 96.36 | gold quality |
| peritoneum | UBERON:0002358 | 96.34 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 96.34 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 96.32 | gold quality |
| right coronary artery | UBERON:0001625 | 96.30 | gold quality |
| lower esophagus | UBERON:0013473 | 96.24 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 96.24 | gold quality |
| sperm | CL:0000019 | 96.23 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 96.22 | gold quality |
| metanephros cortex | UBERON:0010533 | 96.18 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 7.53 |
| E-CURD-112 | no | 3.95 |
| E-MTAB-5061 | no | 3.12 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
71 targeting DNPEP, 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-656-3P | 100.00 | 72.15 | 2788 |
| HSA-LET-7A-3P | 100.00 | 74.03 | 3932 |
| HSA-LET-7B-3P | 100.00 | 74.08 | 3913 |
| HSA-LET-7F-1-3P | 100.00 | 74.02 | 3928 |
| HSA-MIR-98-3P | 100.00 | 74.08 | 3907 |
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-4789-3P | 99.99 | 70.75 | 2484 |
| HSA-MIR-150-5P | 99.99 | 66.69 | 1976 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-MIR-3688-3P | 99.97 | 72.02 | 2834 |
| HSA-MIR-4666A-3P | 99.96 | 71.71 | 3434 |
| HSA-MIR-6778-3P | 99.96 | 67.29 | 2693 |
| HSA-MIR-548AA | 99.96 | 70.64 | 3753 |
| HSA-MIR-548AP-3P | 99.96 | 70.64 | 3753 |
| HSA-MIR-548T-3P | 99.96 | 70.64 | 3753 |
| HSA-MIR-9983-3P | 99.94 | 71.48 | 3631 |
| HSA-MIR-4302 | 99.89 | 67.94 | 1187 |
| HSA-MIR-95-5P | 99.89 | 72.17 | 3973 |
| HSA-MIR-129-5P | 99.88 | 70.26 | 3273 |
| HSA-MIR-4728-5P | 99.85 | 69.39 | 4718 |
| HSA-MIR-6785-5P | 99.82 | 68.68 | 4428 |
| HSA-MIR-6515-3P | 99.82 | 68.19 | 1933 |
| HSA-MIR-2052 | 99.79 | 69.37 | 2031 |
| HSA-MIR-8076 | 99.78 | 68.52 | 1170 |
| HSA-MIR-4524A-3P | 99.72 | 66.85 | 2406 |
| HSA-MIR-149-3P | 99.72 | 68.22 | 3963 |
| HSA-MIR-33A-3P | 99.70 | 70.27 | 3362 |
| HSA-MIR-6883-5P | 99.69 | 68.05 | 3785 |
Literature-anchored findings (GeneRIF, showing 4)
- Identification of histidine residues important in the catalysis and structure of aspartyl aminopeptidase (PMID:12413488)
- The crystal structure of human DNPEP complexed with zinc and a substrate analogue aspartate-beta-hydroxamate reveals a dodecameric machinery built by domain-swapped dimers. (PMID:22720794)
- aspartyl aminopeptidase was upregulated in colorectal cancer tissues, and greater activity correlated significantly with the absence of lymph node metastases and with better overall survival (PMID:23948443)
- Aspartyl Aminopeptidase Suppresses Proliferation, Invasion, and Stemness of Breast Cancer Cells via Targeting CD44. (PMID:31228326)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | dnpep | ENSDARG00000022599 |
| mus_musculus | Dnpep | ENSMUSG00000026209 |
| rattus_norvegicus | Dnpep | ENSRNOG00000019772 |
Protein
Protein identifiers
Aspartyl aminopeptidase — Q9ULA0 (reviewed: Q9ULA0)
All UniProt accessions (14): B9ZVU2, C9J1E2, C9JBE1, C9JRG3, E3W974, E3W979, E5RHR3, E5RIA4, E5RJ35, E7EMB6, E7EPX3, Q9ULA0, E7ETB3, F8WAN0
UniProt curated annotations — full annotation on UniProt →
Function. Aminopeptidase with specificity towards an acidic amino acid at the N-terminus. Likely to play an important role in intracellular protein and peptide metabolism.
Subunit / interactions. Tetrahedron-shaped homododecamer built from six homodimers.
Subcellular location. Cytoplasm.
Tissue specificity. Ubiquitous.
Activity regulation. One of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity.
Cofactor. Binds 2 Zn(2+) ions per subunit.
Similarity. Belongs to the peptidase M18 family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9ULA0-1 | 1 | yes |
| Q9ULA0-2 | 2 |
RefSeq proteins (8): NP_001306045, NP_001306046, NP_001306047, NP_001306048, NP_001306049, NP_001306050, NP_001306051, NP_036232* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001948 | Peptidase_M18 | Family |
| IPR023358 | Peptidase_M18_dom2 | Homologous_superfamily |
Pfam: PF02127
Enzyme classification (BRENDA):
- EC 3.4.11.21 — aspartyl aminopeptidase (BRENDA: 22 organisms, 65 substrates, 174 inhibitors, 26 Km, 4 kcat entries)
Substrate kinetics (BRENDA)
13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| L-ASP-4-NITROANILIDE | 0.092–1.21 | 4 |
| ASP-4-NITROANILIDE | 0.389–5.93 | 3 |
| GLU-4-NITROANILIDE | 0.137–1.05 | 3 |
| ASP-7-AMIDO-4-METHYLCOUMARIN | 0.327–0.385 | 2 |
| ASP-ALA-PRO-SULFAMETHOXAZOLE | 2–2.3 | 2 |
| GLU-7-AMIDO-4-METHYLCOUMARIN | 0.135–0.136 | 2 |
| L-GLU-4-NITROANILIDE | 0.19–25.2 | 2 |
| ANGIOTENSIN I | 0.064 | 1 |
| ANGIOTENSIN II | 0.25 | 1 |
| ASP-ALA-PRO-NAPHTHYLAMIDE | 2 | 1 |
| ASP-XAA | 0.94 | 1 |
| GLU 2-NAPHTHYLAMIDE | 0.35 | 1 |
| GLU-ALA-PRO-NAPHTHYLAMIDE | 8.4 | 1 |
UniProt features (61 total): strand 18, helix 16, binding site 14, turn 7, modified residue 2, sequence conflict 2, chain 1, splice variant 1
Structure
Experimental structures (PDB)
1 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4DYO | X-RAY DIFFRACTION | 2.2 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9ULA0-F1 | 95.95 | 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.
Ligand- & substrate-binding residues (14): 104; 356; 359; 384; 391; 450; 180; 274; 274; 311; 311; 312 …
Post-translational modifications (2): 213, 1
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 0 (showing top):
GO Biological Process (2): proteolysis (GO:0006508), peptide metabolic process (GO:0006518)
GO Molecular Function (8): aminopeptidase activity (GO:0004177), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)
GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), blood microparticle (GO:0072562)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| protein metabolic process | 1 |
| metabolic process | 1 |
| exopeptidase activity | 1 |
| peptidase activity | 1 |
| transition metal ion binding | 1 |
| protein binding | 1 |
| binding | 1 |
| hydrolase activity | 1 |
| catalytic activity, acting on a protein | 1 |
| catalytic activity | 1 |
| cation binding | 1 |
| intracellular membrane-bounded organelle | 1 |
| intracellular anatomical structure | 1 |
| cytoplasm | 1 |
| extracellular region | 1 |
Protein interactions and networks
STRING
1491 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| DNPEP | DPP4 | P27487 | 841 |
| DNPEP | RNPEP | Q9H4A4 | 756 |
| DNPEP | ENPEP | Q07075 | 711 |
| DNPEP | LAP3 | P28838 | 689 |
| DNPEP | PGPEP1 | Q9NXJ5 | 598 |
| DNPEP | ANPEP | P15144 | 585 |
| DNPEP | METAP1 | P53582 | 558 |
| DNPEP | LNPEP | Q9UIQ6 | 557 |
| DNPEP | NPEPPS | P55786 | 557 |
| DNPEP | PREP | P48147 | 525 |
| DNPEP | XPNPEP3 | Q9NQH7 | 521 |
| DNPEP | DPP3 | Q9NY33 | 484 |
| DNPEP | LRRC34 | Q8IZ02 | 464 |
| DNPEP | DUS2 | Q9NX74 | 463 |
| DNPEP | XPNPEP1 | Q9NQW7 | 460 |
IntAct
105 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| DNPEP | LNX1 | psi-mi:“MI:0915”(physical association) | 0.780 |
| LNX1 | DNPEP | psi-mi:“MI:0915”(physical association) | 0.780 |
| MPP1 | DNPEP | psi-mi:“MI:0915”(physical association) | 0.720 |
| DNPEP | MPP1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| CFTR | ESYT2 | psi-mi:“MI:0914”(association) | 0.710 |
| DNPEP | DNPEP | psi-mi:“MI:0915”(physical association) | 0.670 |
| MPPED1 | TXNDC9 | psi-mi:“MI:0914”(association) | 0.640 |
| RAB11B | SH3BP5 | psi-mi:“MI:0914”(association) | 0.640 |
| GPX7 | GAK | psi-mi:“MI:0914”(association) | 0.640 |
| MGME1 | POLG | psi-mi:“MI:0914”(association) | 0.640 |
| DNPEP | SCAF8 | psi-mi:“MI:0915”(physical association) | 0.590 |
| TAE1 | DNPEP | psi-mi:“MI:0915”(physical association) | 0.560 |
| DNPEP | TAE1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| RAB11A | SH3BP5 | psi-mi:“MI:0914”(association) | 0.530 |
BioGRID (112): DNPEP (Two-hybrid), DNPEP (Two-hybrid), LNX1 (Two-hybrid), DNPEP (Affinity Capture-MS), DNPEP (Affinity Capture-MS), DNPEP (Two-hybrid), ADAMTSL4 (Two-hybrid), DNPEP (Two-hybrid), TPI1 (Co-fractionation), DNPEP (Affinity Capture-MS), DNPEP (Affinity Capture-MS), DNPEP (Affinity Capture-MS), DNPEP (Affinity Capture-MS), DNPEP (Affinity Capture-MS), DNPEP (Affinity Capture-MS)
ESM2 similar proteins: A0AVT1, A0JMS7, A2BP19, A6H630, B0C2K7, B3EK39, B3MF31, B4MNL1, B4P925, B4S3A5, P17812, P46446, P50547, P59830, P70698, P72208, Q10VR3, Q1LXS2, Q1RMS2, Q28C61, Q2NL24, Q3MC79, Q58EM4, Q5BJ91, Q5F3Z1, Q5M876, Q5RBT2, Q5XGC5, Q6AXB1, Q6AYT5, Q6DHI0, Q6DHQ3, Q6DJA3, Q7SYV1, Q7TS68, Q8C7R4, Q8R3P0, Q8YQC1, Q91XE4, Q969U7
Diamond homologs: A0PYH7, A1KGT3, A4VJG1, A4XRN0, A5U0I9, A5W7K3, A6V2H4, B0KTU0, B1J1S3, B7V7X2, B9RAJ0, C1ALD5, C1DQM8, C3K0D7, O36014, O51572, P38821, P59951, P9WHT0, P9WHT1, Q02Q78, Q19087, Q1IDE6, Q2HJH1, Q2UPZ7, Q3KFM3, Q48L80, Q4ZW15, Q50022, Q54M70, Q5RBT2, Q82F74, Q87YC5, Q88M44, Q97LF4, Q9HYZ3, Q9ULA0, Q9XA76, Q9Z2W0, P14904
SIGNOR signaling
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| PAK5 | “down-regulates quantity by destabilization” | DNPEP | phosphorylation |
| DNPEP | “down-regulates quantity by destabilization” | USP4 | cleavage |
Disease & clinical
Clinical variants and AI predictions
ClinVar
99 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 80 |
| Likely benign | 2 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
2173 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 2:219374849:TGTTA:T | donor_loss | 1.0000 |
| 2:219374850:GTTAC:G | donor_loss | 1.0000 |
| 2:219374851:TTACC:T | donor_loss | 1.0000 |
| 2:219374852:TACCT:T | donor_loss | 1.0000 |
| 2:219374853:A:AG | donor_loss | 1.0000 |
| 2:219374854:CCT:C | donor_loss | 1.0000 |
| 2:219375021:TC:T | acceptor_gain | 1.0000 |
| 2:219375021:TCC:T | acceptor_loss | 1.0000 |
| 2:219375022:CC:C | acceptor_gain | 1.0000 |
| 2:219375022:CCTA:C | acceptor_loss | 1.0000 |
| 2:219375023:C:CA | acceptor_loss | 1.0000 |
| 2:219375023:C:CC | acceptor_gain | 1.0000 |
| 2:219375024:T:C | acceptor_loss | 1.0000 |
| 2:219381331:TCAC:T | donor_loss | 1.0000 |
| 2:219381332:CACC:C | donor_loss | 1.0000 |
| 2:219381333:A:AG | donor_loss | 1.0000 |
| 2:219381334:CCTGC:C | donor_loss | 1.0000 |
| 2:219381434:GCCC:G | acceptor_loss | 1.0000 |
| 2:219381435:CC:C | acceptor_gain | 1.0000 |
| 2:219381436:CC:C | acceptor_gain | 1.0000 |
| 2:219381437:C:CC | acceptor_gain | 1.0000 |
| 2:219381438:T:A | acceptor_loss | 1.0000 |
| 2:219381539:TCTCA:T | donor_loss | 1.0000 |
| 2:219381540:CTCAC:C | donor_loss | 1.0000 |
| 2:219381541:TCACC:T | donor_loss | 1.0000 |
| 2:219381542:CA:C | donor_loss | 1.0000 |
| 2:219381544:C:T | donor_loss | 1.0000 |
| 2:219383221:C:CT | acceptor_gain | 1.0000 |
| 2:219383222:A:T | acceptor_gain | 1.0000 |
| 2:219384441:GACCT:G | acceptor_loss | 1.0000 |
AlphaMissense
3166 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 2:219384397:T:A | D274V | 0.999 |
| 2:219382009:T:A | D356V | 0.998 |
| 2:219382014:G:C | S354R | 0.998 |
| 2:219382014:G:T | S354R | 0.998 |
| 2:219382016:T:G | S354R | 0.998 |
| 2:219384396:G:C | D274E | 0.998 |
| 2:219384396:G:T | D274E | 0.998 |
| 2:219384397:T:G | D274A | 0.998 |
| 2:219374901:T:A | E454V | 0.997 |
| 2:219382008:G:C | D356E | 0.997 |
| 2:219382008:G:T | D356E | 0.997 |
| 2:219382009:T:G | D356A | 0.997 |
| 2:219383135:T:A | E311V | 0.997 |
| 2:219384381:G:C | C279W | 0.997 |
| 2:219384393:A:C | N275K | 0.997 |
| 2:219384393:A:T | N275K | 0.997 |
| 2:219386330:A:G | W139R | 0.997 |
| 2:219386330:A:T | W139R | 0.997 |
| 2:219386940:G:C | F57L | 0.997 |
| 2:219386940:G:T | F57L | 0.997 |
| 2:219386942:A:G | F57L | 0.997 |
| 2:219374904:C:G | R453P | 0.996 |
| 2:219383134:T:A | E311D | 0.996 |
| 2:219383134:T:G | E311D | 0.996 |
| 2:219386320:C:G | R142P | 0.996 |
| 2:219386915:A:G | W66R | 0.996 |
| 2:219386915:A:T | W66R | 0.996 |
| 2:219374991:C:T | G424E | 0.995 |
| 2:219382010:C:G | D356H | 0.995 |
| 2:219384398:C:G | D274H | 0.995 |
dbSNP variants (sampled 300 via entrez): RS1000186868 (2:219400070 T>C,G), RS1000288318 (2:219399979 C>G), RS1000337377 (2:219393679 C>T), RS1000361531 (2:219399703 A>G), RS1000384700 (2:219400333 C>T), RS1000389019 (2:219380666 C>G,T), RS1000517941 (2:219392155 A>C,G), RS1000634587 (2:219393749 C>G), RS1001000552 (2:219375433 G>C), RS1001039529 (2:219381726 A>G,T), RS1001167586 (2:219401270 T>C), RS1001231348 (2:219395070 C>T), RS1001354802 (2:219401075 G>A), RS1001510504 (2:219375623 G>A), RS1001596618 (2:219376820 G>A,C)
Disease associations
OMIM: gene MIM:611367 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
4 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST002069_2 | Systemic lupus erythematosus and Systemic sclerosis | 2.000000e-07 |
| GCST008839_309 | Height | 2.000000e-09 |
| GCST009733_76 | Urinary metabolite levels in chronic kidney disease | 4.000000e-11 |
| GCST011742_24 | Triglyceride levels in HIV infection | 8.000000e-06 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0005116 | urinary metabolite measurement |
| EFO:0004530 | triglyceride measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL2761 (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 — M18: Aminopeptidase I
Most potent curated ligand interactions (1 total), top 1:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| compound 9 [PMID: 1738140] | Inhibition | 6.29 | pKi |
ChEMBL bioactivities
6 potent at pChembl≥5 of 7 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 6.29 | Ki | 510 | nM | CHEMBL309130 |
| 6.00 | Ki | 1000 | nM | CHEMBL143589 |
| 5.82 | Kd | 1530 | nM | CHEMBL5653589 |
| 5.82 | ED50 | 1530 | nM | CHEMBL5653589 |
| 5.72 | Ki | 1900 | nM | CHEMBL140846 |
| 5.27 | Ki | 5400 | nM | CHEMBL142010 |
PubChem BioAssay actives
5 with measured affinity, of 19 total; 5 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,3R)-3-amino-2-hydroxy-N-(3-methylbutyl)-4-phenylbutanamide | 35693: Compound was tested for binding affinity towards cytosolic aminopeptidase | ki | 0.5100 | uM |
| 3-amino-N-(3-methylbutyl)-2-oxo-4-phenylbutanamide | 35693: Compound was tested for binding affinity towards cytosolic aminopeptidase | ki | 1.0000 | uM |
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148256: Binding affinity to human DNPEP incubated for 45 mins by Kinobead based pull down assay | kd | 1.5296 | uM |
| (3S)-3-amino-5-methyl-N-(3-methylbutyl)-2-oxohexanamide | 35693: Compound was tested for binding affinity towards cytosolic aminopeptidase | ki | 1.9000 | uM |
| (2S,3R)-3-amino-2-hydroxy-5-methyl-N-(3-methylbutyl)hexanamide | 55259: Compound was tested for binding affinity towards Cytosolic aminopeptidase | ki | 5.4000 | uM |
CTD chemical–gene interactions
34 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| methacrylaldehyde | affects cotreatment, decreases expression, increases oxidation, increases abundance | 2 |
| Acrolein | decreases expression, increases oxidation, increases abundance, affects cotreatment | 2 |
| Ozone | affects cotreatment, decreases expression, increases oxidation, increases abundance | 2 |
| Cadmium Chloride | increases expression | 2 |
| alpha-pinene | increases oxidation, increases abundance, affects cotreatment, decreases expression | 1 |
| pirinixic acid | increases expression, affects binding, increases activity | 1 |
| beta-lapachone | increases expression | 1 |
| sodium arsenite | affects expression | 1 |
| cobaltous chloride | increases expression | 1 |
| potassium chromate(VI) | affects cotreatment, decreases expression | 1 |
| epigallocatechin gallate | affects cotreatment, decreases expression | 1 |
| perfluorooctane sulfonic acid | increases expression | 1 |
| nutlin 3 | affects cotreatment, increases secretion | 1 |
| ICG 001 | increases expression | 1 |
| 3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol | increases expression | 1 |
| Air Pollutants | affects cotreatment, decreases expression, increases abundance, increases oxidation | 1 |
| Atrazine | increases expression | 1 |
| Vehicle Emissions | increases abundance, increases expression | 1 |
| Benzo(a)pyrene | decreases methylation | 1 |
| Bilirubin | decreases expression | 1 |
| Dactinomycin | affects cotreatment, increases secretion | 1 |
| Doxorubicin | decreases expression | 1 |
| Ivermectin | decreases expression | 1 |
| Lead | decreases expression | 1 |
| Rotenone | decreases expression | 1 |
| Selenium | increases expression | 1 |
| Smoke | decreases expression | 1 |
| Urethane | decreases expression | 1 |
| Valproic Acid | decreases expression | 1 |
| Cyclosporine | increases expression | 1 |
ChEMBL screening assays
11 unique, capped per target: 10 binding, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4118714 | Binding | Binding affinity to DNPEP in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay | Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem |
| 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 |
Cellosaurus cell lines
3 cell lines: 3 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_D1MA | Abcam K-562 DNPEP KO | Cancer cell line | Female |
| CVCL_D2IV | Abcam Raji DNPEP KO | Cancer cell line | Male |
| CVCL_UQ42 | Abcam Jurkat DNPEP KO | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): systemic sclerosis