DPP9

Summary

DPP9 (dipeptidyl peptidase 9, HGNC:18648) is a protein-coding gene on chromosome 19p13.3, encoding Dipeptidyl peptidase 9 (Q86TI2). Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.

This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound. In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized.

Source: NCBI Gene 91039 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hatipoglu immunodeficiency syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 198 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_139159

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18648
Approved symbol	DPP9
Name	dipeptidyl peptidase 9
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142002
Ensembl biotype	protein_coding
OMIM	608258
Entrez	91039

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 13 protein_coding, 13 protein_coding_CDS_not_defined, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000262960, ENST00000593973, ENST00000594671, ENST00000595327, ENST00000595940, ENST00000597024, ENST00000597145, ENST00000597253, ENST00000597726, ENST00000597849, ENST00000597900, ENST00000598041, ENST00000598360, ENST00000598800, ENST00000599163, ENST00000599248, ENST00000599998, ENST00000600497, ENST00000600556, ENST00000600621, ENST00000601130, ENST00000601173, ENST00000601720, ENST00000601764, ENST00000602161, ENST00000646573, ENST00000703253, ENST00000703254, ENST00000703255, ENST00000855532, ENST00000855533, ENST00000855534, ENST00000922035, ENST00000955625

RefSeq mRNA: 30 — MANE Select: NM_139159 NM_001365987, NM_001384611, NM_001384612, NM_001384613, NM_001384614, NM_001384615, NM_001384616, NM_001384617, NM_001384618, NM_001384619, NM_001384620, NM_001384621, NM_001384622, NM_001384623, NM_001384624, NM_001384625, NM_001384626, NM_001384627, NM_001384628, NM_001384629, NM_001384630, NM_001384631, NM_001384632, NM_001384633, NM_001384634, NM_001384635, NM_001384636, NM_001384637, NM_001384638, NM_139159

CCDS: CCDS45928, CCDS92491, CCDS92492

Canonical transcript exons

ENST00000262960 — 22 exons

Exon	Start	End
ENSE00001664703	4722499	4722551
ENSE00001719243	4675227	4676656
ENSE00001720699	4684663	4684809
ENSE00003521481	4679835	4679946
ENSE00003545713	4719851	4719941
ENSE00003550866	4683477	4683629
ENSE00003567091	4682696	4682838
ENSE00003693297	4714081	4714337
ENSE00003827533	4685626	4685771
ENSE00003980737	4723674	4723842
ENSE00003988186	4700216	4700277
ENSE00003988187	4702027	4702155
ENSE00003988189	4697551	4697651
ENSE00003988190	4703886	4704054
ENSE00003988191	4689570	4689722
ENSE00003988192	4688757	4688892
ENSE00003988193	4690878	4690957
ENSE00003988194	4694661	4694823
ENSE00003988195	4704131	4704304
ENSE00003988196	4702603	4702716
ENSE00003988199	4695378	4695555
ENSE00003988200	4705858	4705970

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 94.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7327 / max 183.3407, expressed in 1820 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178491	27.9914	1818
178487	0.7404	172
178489	0.6961	284
178490	0.1043	54
178485	0.0689	7
178488	0.0559	18
208658	0.0462	18
178486	0.0295	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	94.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.00	gold quality
right lobe of liver	UBERON:0001114	93.93	gold quality
muscle of leg	UBERON:0001383	93.73	gold quality
granulocyte	CL:0000094	93.27	gold quality
pancreatic ductal cell	CL:0002079	92.51	silver quality
vermiform appendix	UBERON:0001154	91.81	gold quality
upper lobe of left lung	UBERON:0008952	91.72	gold quality
skeletal muscle organ	UBERON:0014892	91.43	gold quality
mucosa of transverse colon	UBERON:0004991	91.33	gold quality
colonic epithelium	UBERON:0000397	91.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.25	gold quality
apex of heart	UBERON:0002098	91.21	gold quality
skin of leg	UBERON:0001511	90.99	gold quality
stromal cell of endometrium	CL:0002255	90.96	gold quality
sural nerve	UBERON:0015488	90.93	gold quality
transverse colon	UBERON:0001157	90.92	gold quality
bone marrow cell	CL:0002092	90.73	gold quality
skin of abdomen	UBERON:0001416	90.60	gold quality
lower esophagus	UBERON:0013473	90.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.34	gold quality
spleen	UBERON:0002106	90.30	gold quality
upper lobe of lung	UBERON:0008948	90.21	gold quality
ectocervix	UBERON:0012249	90.20	gold quality
lower esophagus mucosa	UBERON:0035834	90.19	gold quality
heart left ventricle	UBERON:0002084	90.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.07	gold quality
small intestine	UBERON:0002108	89.95	gold quality
right lung	UBERON:0002167	89.93	gold quality
body of stomach	UBERON:0001161	89.91	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	no	3.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• identification of two forms, their tissue distribution, cytoplasmic localization (PMID:15245913)
• cells overexpressing DP9 exhibit behavioral changesin the presence of ECM components; these effects were independent of enzyme activity (PMID:16700509)
• Dipeptidyl peptidase 8 and dipeptidyl peptidase 9 influence cell-extracellular matrix interactions, and thus may regulate tissue remodeling. (PMID:16704418)
• The DPP9 gene is not associated with the occurrence or curve severity of AIS. It is neither a disease-predisposition nor a disease-modifying gene of AIS. (PMID:18940951)
• results indicate that the biochemical property of DPP9 is very similar to that of DPP8, its homologous protease. DPP9 and DPP8 are likely redundant proteins carrying out overlapping functions in vivo (PMID:19268648)
• DP8 and DP9 tissue and cellular expression (PMID:19581630)
• DPP9, a poorly characterized cytoplasmic prolyl-peptidase, is rate-limiting for destruction of proline-containing substrates both in cell extracts and in intact cells (PMID:19667070)
• DPP8 and DPP9 prevail over canonical DPP-IV/CD26 and FAPalpha in all examined meningioma patients (PMID:20043068)
• This is the first study to demonstrate the presence of DP9 in chronic lymphocytic leukemia. (PMID:20534982)
• These findings suggest an important signaling role of DPP9 in the regulation of survival and proliferation pathways. (PMID:21622624)
• Data identify modification points in the topology of a representative DPP8/9-inhibitor, capable of rendering selectivity for DPP8 over DPP9. (PMID:21711053)
• residues important for dimer formation and enzymatic activity (PMID:22001206)
• this study demonstrates for the first time that DP8 and DP9 are expressed in breast and ovarian carcinoma cell lines (PMID:22736146)
• DPP9 binds to SUMO1 through a novel SUMO1 interacting motif. (PMID:23152501)
• analysis of dipeptidyl peptidases 8 and 9 reveals that they may have compensatory roles (PMID:23519473)
• DPP9 was found in macrophages of carotid atherosclerotic plaque and may play a role in disease progression. (PMID:23608773)
• Suggest roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis. (PMID:23704821)
• The SUMO1-E67 interacting loop peptide is an allosteric inhibitor of the dipeptidyl peptidases 8 and 9. (PMID:24072711)
• Whereas DPP9-short is present in the cytosol, DPP9-long localizes preferentially to the nucleus. (PMID:24562348)
• The DPP9 expressing cell model system is a very useful and promising system for investigating the selectivity and associated toxicity of DPP4 inhibitors on DPP9. (PMID:25464020)
• There was a concomitant decrease in the phosphorylation of focal adhesion kinase and paxillin, indicating that DPP9 knockdown or enzyme inhibition suppressed the associated adhesion signaling pathway, causing impaired cell movement. (PMID:25486458)
• The data of this study have shown that fibroblasts and keratinocytes of normal skin endogenously express DPP9 both at transcriptional and protein level. It is localized intracellularly, mostly in cytoplasm, whereby the sub-localization within Golgi is very scarce. (PMID:27682012)
• DPP9 has a role in promoting tumorgenicity, metastasis and the prediction of poor prognosis in non-small cell lung cancer (PMID:27943262)
• we found a DPP9-PPP6R3 fusion transcript in one tumor showing a matching genomic 11;19-translocation. Another tumor had a rearrangement of DPP9 with PLIN3. Both rearrangements were associated with diminished expression of the 3’ end of DPP9 corresponding to the breakpoints identified by RNA-seq. (PMID:28893231)
• DPP9 is an interacting partner of human NLRP1 and a related, human-specific inflammasome regulator, CARD8, and binds the autoproteolytic FIIND domain of both proteins. (PMID:30291141)
• Dipeptidyl Peptidase 9 Increases Chemoresistance and is an Indicator of Poor Prognosis in Colorectal Cancer. (PMID:32734369)
• Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import. (PMID:32815200)
• Decrease of the pro-inflammatory M1-like response by inhibition of dipeptidyl peptidases 8/9 in THP-1 macrophages - quantitative proteomics of the proteome and secretome. (PMID:32998073)
• Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. (PMID:33731929)
• DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. (PMID:33731932)
• DPP9 restrains NLRP1 activation. (PMID:33785922)
• Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells. (PMID:33932609)
• Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment. (PMID:34019797)
• CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender. (PMID:35131543)
• Inflammasome sensor NLRP1 disease variant M1184V promotes autoproteolysis and DPP9 complex formation by stabilizing the FIIND domain. (PMID:36309085)
• Hemophagocytic lymphohistiocytosis-like hyperinflammation due to a de novo mutation in DPP9. (PMID:37544411)
• DPP9 Stabilizes NRF2 to Suppress Ferroptosis and Induce Sorafenib Resistance in Clear Cell Renal Cell Carcinoma. (PMID:37713596)
• DPP8/9 inhibition attenuates the TGF-beta1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathways. (PMID:38458339)
• Dipeptidyl-peptidase 9 regulates the dynamics of tumorigenesis and metastasis in breast cancer. (PMID:38531482)
• DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells. (PMID:39094401)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpp9	ENSDARG00000052606
mus_musculus	Dpp9	ENSMUSG00000001229
rattus_norvegicus	Dpp9	ENSRNOG00000050748
drosophila_melanogaster	CG3744	FBGN0039240
caenorhabditis_elegans	dpf-3	WBGENE00001056

Paralogs (6): DPP8 (ENSG00000074603), FAP (ENSG00000078098), DPP6 (ENSG00000130226), APEH (ENSG00000164062), DPP10 (ENSG00000175497), DPP4 (ENSG00000197635)

Protein

Protein identifiers

Dipeptidyl peptidase 9 — Q86TI2 (reviewed: Q86TI2)

Alternative names: Dipeptidyl peptidase IV-related protein 2, Dipeptidyl peptidase IX, Dipeptidyl peptidase-like protein 9

All UniProt accessions (7): Q86TI2, A0A2R8YF65, A0A8V8TR99, M0QZ97, M0R145, M0R2A8, M0R2G6

UniProt curated annotations — full annotation on UniProt →

Function. Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8. Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation. The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP9, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition.

Subunit / interactions. Homodimer. Forms a ternary complex with NLRP1, composed of a DPP9 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus). Forms a ternary complex with CARD8, composed of a DPP9 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus). In the ternary complex, only one subunit of the DPP9 homodimer is bound to NLRP1 or CARD8.

Subcellular location. Cytoplasm. Cytosol Nucleus.

Tissue specificity. Ubiquitously expressed, with highest levels in liver, heart and muscle, and lowest levels in brain.

Disease relevance. Hatipoglu immunodeficiency syndrome (HATIS) [MIM:620331] An autosomal recessive immunologic disorder manifesting in infancy or early childhood, and characterized by failure to thrive, short stature, skin pigmentation abnormalities, pancytopenia, and susceptibility to recurrent infections. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate. Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages. Val-boroPro inhibits activity by binding to the active site, mimicking a substrate-bound state, thereby displacing the C-terminal fragment of NLRP1, leading to activation of the NLRP1 inflammasome. In contrast, Val-boroPro does not directly displaces CARD8: it acts by promoting degradation of the N-terminal part of CARD8, leading to indirect disruption of the ternary complex. Chemical inhibition of DPP9 by Val-boroPro in HIV-1-infected cells activates the CARD8 inflammasome, triggering cell death, offering a promising strategy for the elimination of HIV-1 reservoirs in people living with HIV-1.

Miscellaneous. Active peptidase. Contains a nuclear localization signal at positions 2-9.

Similarity. Belongs to the peptidase S9B family. DPPIV subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86TI2-1	1, DPP9-S, Short	yes
Q86TI2-2	2, DPP9-L, Long
Q86TI2-4	3

RefSeq proteins (30): NP_001352916, NP_001371540, NP_001371541, NP_001371542, NP_001371543, NP_001371544, NP_001371545, NP_001371546, NP_001371547, NP_001371548, NP_001371549, NP_001371550, NP_001371551, NP_001371552, NP_001371553, NP_001371554, NP_001371555, NP_001371556, NP_001371557, NP_001371558, NP_001371559, NP_001371560, NP_001371561, NP_001371562, NP_001371563, NP_001371564, NP_001371565, NP_001371566, NP_001371567, NP_631898* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001375	Peptidase_S9_cat	Domain
IPR002469	Peptidase_S9B_N	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR045785	Dpp_8/9_N	Domain
IPR050278	Serine_Prot_S9B/DPPIV	Family

Pfam: PF00326, PF00930, PF19520

Enzyme classification (BRENDA):

• EC 3.4.13.19 — membrane dipeptidase (BRENDA: 12 organisms, 121 substrates, 55 inhibitors, 49 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
GLY-D-PHE	0.77–12.5	4
L-ARG-L-ASP	1.8–8.8	4
L-CYSTINYL-BIS-GLY	0.45–2.5	3
L-LEU-L-LEU	0.056–1.4	3
GLYCYLDEHYDROPHENYLALANINE	0.102–1	2
LEUKOTRIENE D4	0.005–0.01	2
BETA-LACTAM	0.111	1
GLY-L-LEU	1.22	1
GLY-L-PHE	0.99	1
GLY-L-TRP	2.03	1
GLY-L-VAL	11	1
GLY-LEU	0.79	1
L-ALA-D-ALA	4.4	1
L-ALA-GLY	0.8	1
L-ALA-L-ASP	13.8	1

UniProt features (116 total): strand 59, helix 22, turn 10, mutagenesis site 6, sequence conflict 5, sequence variant 4, active site 3, splice variant 2, initiator methionine 1, chain 1, region of interest 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7ZXS	X-RAY DIFFRACTION	1.81
9GOC	X-RAY DIFFRACTION	1.89
9GON	X-RAY DIFFRACTION	1.89
7SVL	X-RAY DIFFRACTION	2.46
9GOD	X-RAY DIFFRACTION	2.49
7SVN	X-RAY DIFFRACTION	2.78
6EOR	X-RAY DIFFRACTION	2.9
6X6C	ELECTRON MICROSCOPY	2.9
7A3F	X-RAY DIFFRACTION	2.9
6EOQ	X-RAY DIFFRACTION	3
6QZV	X-RAY DIFFRACTION	3
7JKQ	ELECTRON MICROSCOPY	3.3
7JN7	ELECTRON MICROSCOPY	3.3
6X6A	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TI2-F1	92.96	0.83

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 (3): 730 (charge relay system); 808 (charge relay system); 840 (charge relay system)

Ligand- & substrate-binding residues (1): 730 (covalent)

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (6):

Position	Phenotype
96–97	reduced interaction with card8 without affecting the peptidase activity.
100–101	reduced interaction with nlrp1 and card8 without affecting the peptidase activity.
102–103	reduced interaction with card8 without affecting the peptidase activity.
102	reduced interaction with nlrp1 without affecting the peptidase activity.
597	reduced interaction with nlrp1 without affecting the peptidase activity.
730	abolished dipeptidyl peptidase activity and ability to sequester nlrp1 and inhibit pyroptosis.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 282 (showing top): GOBP_INFLAMMATORY_RESPONSE, CAGCTG_AP4_Q5, ATTCTTT_MIR186, GOBP_PROTEOLYSIS, chr19p13, GOCC_CELL_LEADING_EDGE, GOMF_PEPTIDASE_ACTIVITY, GOMF_AMINOPEPTIDASE_ACTIVITY, GOMF_DIPEPTIDYL_PEPTIDASE_ACTIVITY, GOMF_EXOPEPTIDASE_ACTIVITY, GOBP_PYROPTOTIC_INFLAMMATORY_RESPONSE, DELACROIX_RARG_BOUND_MEF, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOCC_SUPRAMOLECULAR_POLYMER

GO Biological Process (7): proteolysis (GO:0006508), negative regulation of programmed cell death (GO:0043069), pyroptotic inflammatory response (GO:0070269), protein maturation (GO:0051604), CARD8 inflammasome complex assembly (GO:0140633), pyroptotic cell death (GO:0141201), NLRP1 inflammasome complex assembly (GO:1904784)

GO Molecular Function (7): aminopeptidase activity (GO:0004177), serine-type peptidase activity (GO:0008236), dipeptidyl-peptidase activity (GO:0008239), identical protein binding (GO:0042802), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), microtubule (GO:0005874), cell leading edge (GO:0031252), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	2
programmed cell death	2
canonical inflammasome complex assembly	2
exopeptidase activity	2
regulation of programmed cell death	1
negative regulation of cellular process	1
inflammatory response	1
gene expression	1
pyroptotic inflammatory response	1
peptidase activity	1
serine hydrolase activity	1
protein binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPP9	PREP	P48147	946
DPP9	DPP7	Q9UHL4	877
DPP9	TFDP3	Q5H9I0	777
DPP9	CARD8	Q9Y2G2	737
DPP9	HRK	O00198	660
DPP9	LZTFL1	Q9NQ48	606
DPP9	FAM13A	O94988	571
DPP9	IFNAR2	P48551	571
DPP9	ATP11A	P98196	571
DPP9	SLC6A20	Q9NP91	568
DPP9	GCG	P01275	524
DPP9	SPPL2C	Q8IUH8	519
DPP9	OAS1	P00973	506
DPP9	TYK2	P29597	492
DPP9	PYDC1	Q8WXC3	486

IntAct

80 interactions, top by confidence:

A	B	Type	Score
MRFAP1	MORF4L2	psi-mi:“MI:0914”(association)	0.950
STAT2	STAT1	psi-mi:“MI:0914”(association)	0.930
SNAI1	KDM1A	psi-mi:“MI:0914”(association)	0.830
DMTN	YWHAG	psi-mi:“MI:0914”(association)	0.670
PTGR3	DBT	psi-mi:“MI:0914”(association)	0.640
DPP9	DPP9	psi-mi:“MI:0407”(direct interaction)	0.560
COX5B	COX7A2L	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
STAT2	INPPL1	psi-mi:“MI:0914”(association)	0.530
DCT	CANX	psi-mi:“MI:0914”(association)	0.530
PLPPR2	METAP2	psi-mi:“MI:0914”(association)	0.530
NEFL	RABEP1	psi-mi:“MI:0914”(association)	0.530
ISCA2	SLMAP	psi-mi:“MI:0914”(association)	0.530
SPDYC	CDK1	psi-mi:“MI:0914”(association)	0.530
ANKRD10	DPP9	psi-mi:“MI:0915”(physical association)	0.500
incE	SNX2	psi-mi:“MI:0914”(association)	0.430
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	WDR46	psi-mi:“MI:0914”(association)	0.350
Bach1	SYNM	psi-mi:“MI:0914”(association)	0.350
PARD6A		psi-mi:“MI:0914”(association)	0.350
GRIA2	NCOA4	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (592): DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Co-fractionation), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), DPP9 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QP51, E9PYK3, E9Q4Z2, G1SPE9, O00763, O15228, O23617, P13676, P13798, P19205, P25154, P35574, P80227, P83006, P98192, Q10MJ1, Q2PQH8, Q338C0, Q496Z0, Q5EBA1, Q5IH13, Q5IH14, Q5R5S1, Q5U5V2, Q5ZIB9, Q641Y5, Q6V1X1, Q6YXW6, Q80YA7, Q80YD1, Q80ZK9, Q86TI2, Q8BVG4, Q8C0P5, Q8C5P5, Q8IYB8, Q8K4M9, Q8N5D0, Q8R146, Q8VZF3

Diamond homologs: A0A2R8QP51, A1CHP1, A1CJQ1, A1D7R6, A2QEK7, A4QYQ5, A6SL49, A7EQZ1, B0XYK8, B1A4F7, B2A951, B2RJX3, B2WC36, B6QVW4, B8MTH6, B8N076, C1GT79, C4JHY5, C5FYZ3, C7YYG9, D1Z9B4, D4AQT0, E3QKD2, E3S9K3, E4UYL6, E9ETL5, Q0CXB1, Q0IXP9, Q18253, Q2HF90, Q2UPW4, Q4WX13, Q6V1X1, Q7JKY3, Q7MUW6, Q7SHU8, Q80YA7, Q86TI2, Q8BVG4, Q96VT7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	138
Likely benign	20
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2500000	NM_139159.5(DPP9):c.2551C>T (p.Gln851Ter)	Pathogenic
2500001	NM_139159.5(DPP9):c.331C>T (p.Arg111Ter)	Pathogenic
3256926	NM_139159.5(DPP9):c.2178G>A (p.Met726Ile)	Likely pathogenic
4277662	NM_139159.5(DPP9):c.2482C>T (p.Arg828Cys)	Likely pathogenic

SpliceAI

4719 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4679944:GGCC:G	acceptor_loss	1.0000
19:4679945:GCCT:G	acceptor_loss	1.0000
19:4679946:CCTG:C	acceptor_loss	1.0000
19:4679947:C:A	acceptor_loss	1.0000
19:4679947:C:CC	acceptor_gain	1.0000
19:4679948:T:A	acceptor_loss	1.0000
19:4682690:CCTTA:C	donor_loss	1.0000
19:4682693:TA:T	donor_loss	1.0000
19:4682694:A:AC	donor_gain	1.0000
19:4682694:AC:A	donor_loss	1.0000
19:4682694:ACT:A	donor_gain	1.0000
19:4682695:C:CT	donor_gain	1.0000
19:4682695:CT:C	donor_gain	1.0000
19:4682695:CTC:C	donor_gain	1.0000
19:4682695:CTCA:C	donor_gain	1.0000
19:4682698:A:AC	donor_gain	1.0000
19:4682699:T:C	donor_gain	1.0000
19:4682834:GCCAC:G	acceptor_gain	1.0000
19:4682835:CCAC:C	acceptor_gain	1.0000
19:4682835:CCACC:C	acceptor_gain	1.0000
19:4682836:CAC:C	acceptor_gain	1.0000
19:4682836:CACC:C	acceptor_gain	1.0000
19:4682837:AC:A	acceptor_gain	1.0000
19:4682837:ACCTG:A	acceptor_loss	1.0000
19:4682838:CC:C	acceptor_gain	1.0000
19:4682838:CCTGA:C	acceptor_loss	1.0000
19:4682839:C:CA	acceptor_loss	1.0000
19:4682839:C:CC	acceptor_gain	1.0000
19:4682839:C:T	acceptor_gain	1.0000
19:4682840:T:A	acceptor_loss	1.0000

AlphaMissense

5894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4676580:A:G	L859P	1.000
19:4676636:G:C	H840Q	1.000
19:4676636:G:T	H840Q	1.000
19:4676637:T:C	H840R	1.000
19:4676638:G:C	H840D	1.000
19:4676638:G:T	H840N	1.000
19:4676639:T:A	R839S	1.000
19:4676639:T:G	R839S	1.000
19:4676640:C:A	R839I	1.000
19:4676653:A:C	Y835D	1.000
19:4679902:A:T	V811E	1.000
19:4679904:G:C	N810K	1.000
19:4679904:G:T	N810K	1.000
19:4679905:T:A	N810I	1.000
19:4679906:T:C	N810D	1.000
19:4679906:T:G	N810H	1.000
19:4679908:T:A	E809V	1.000
19:4679910:G:C	D808E	1.000
19:4679910:G:T	D808E	1.000
19:4679911:T:A	D808V	1.000
19:4679911:T:G	D808A	1.000
19:4679912:C:A	D808Y	1.000
19:4679912:C:G	D808H	1.000
19:4679920:C:T	G805D	1.000
19:4679921:C:G	G805R	1.000
19:4679932:A:G	L801P	1.000
19:4682787:A:G	Y766H	1.000
19:4682799:A:G	Y762H	1.000
19:4682808:A:G	W759R	1.000
19:4682808:A:T	W759R	1.000

dbSNP variants (sampled 300 via entrez): RS1000084817 (19:4722592 G>A), RS1000196516 (19:4724171 T>C), RS1000202622 (19:4703273 C>A,T), RS1000267748 (19:4699377 C>A,G,T), RS1000303806 (19:4719826 T>C), RS1000320541 (19:4701372 G>A), RS1000595091 (19:4690765 A>C), RS1000632214 (19:4686868 C>T), RS1000692016 (19:4721313 T>C), RS1000706120 (19:4695207 C>G,T), RS1000752076 (19:4716077 G>A), RS1000784502 (19:4716360 G>A), RS1000895893 (19:4676041 G>A), RS1000940978 (19:4724125 G>A,C,T), RS1000969100 (19:4714897 A>G)

Disease associations

OMIM: gene MIM:608258 | disease phenotypes: MIM:620331

GenCC curated gene-disease

Disease	Classification	Inheritance
hatipoglu immunodeficiency syndrome	Strong	Autosomal recessive
autoinflammatory syndrome	Strong	Autosomal dominant

Mondo (2): hatipoglu immunodeficiency syndrome (MONDO:0957229), autoinflammatory syndrome (MONDO:0019751)

Orphanet (0):

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000337	Broad forehead
HP:0000403	Recurrent otitis media
HP:0000494	Downslanted palpebral fissures
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000967	Petechiae
HP:0000970	Anhidrosis
HP:0001047	Atopic dermatitis
HP:0001058	Poor wound healing
HP:0001063	Acrocyanosis
HP:0001072	Thickened skin
HP:0001328	Specific learning disability
HP:0001350	Slurred speech
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001876	Pancytopenia
HP:0001903	Anemia
HP:0001954	Recurrent fever
HP:0002020	Gastroesophageal reflux
HP:0002099	Asthma
HP:0002110	Bronchiectasis
HP:0002206	Pulmonary fibrosis
HP:0002216	Premature graying of hair
HP:0002286	Fair hair

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001968_9	Interstitial lung disease	2.000000e-12
GCST009758_15	Idiopathic pulmonary fibrosis	3.000000e-12
GCST90000255_18	Severe COVID-19 infection with respiratory failure (analysis I)	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000768	idiopathic pulmonary fibrosis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885564 (PROTEIN FAMILY), CHEMBL4793 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 84,552 (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
CHEMBL1422	SITAGLIPTIN	4	26,582
CHEMBL142703	VILDAGLIPTIN	4	20,312
CHEMBL2147777	TENELIGLIPTIN	4	1,406
CHEMBL237500	LINAGLIPTIN	4	5,282
CHEMBL385517	SAXAGLIPTIN ANHYDROUS	4	18,553
CHEMBL515387	GOSOGLIPTIN	4	785
CHEMBL67279	TALABOSTAT	3	10,259
CHEMBL4296719	DUTOGLIPTIN	3	1,373

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S9: Prolyl oligopeptidase

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
talabostat	Inhibition	9.12	pKi
ICeD-2	Inhibition	9.05	pIC50
compound 42 [PMID: 37721854]	Inhibition	8.47	pIC50
1G244	Inhibition	7.28	pIC50
compound 24dd [PMID: 20684603]	Inhibition	6.72	pKi
vildagliptin	Inhibition	6.64	pIC50
tominostat	Inhibition	6.59	pIC50
teneligliptin	Inhibition	6.27	pIC50
compound 9 [PMID: 20718420]	Inhibition	5.57	pIC50

Binding affinities (BindingDB)

250 measured of 333 human assays (337 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2S)-1-[(2S)-2-amino-2-cyclopentylacetyl]pyrrolidine-2-carbonitrile	KI	1 nM
2-[4-{{2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4-methyl-1-piperidinyl]-4-pyridinecarboxylic Acid	KI	1 nM
6-[4-({2-[(2S,5R)-2-cyano-5-ethynylpyrrolidin-1-yl]-2-oxoethyl}amino)-4-methylpiperidin-1-yl]pyridine-3-carboxylic acid	KI	1.3 nM
(1S,6R)-3-{[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[3,4-a]pyrazin-7-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	1.3 nM
(3R, 4R)-1-(6-(3, 3-Difluoropyrrolidin-1-yl)pyrimidin-4-yl)-4-(2, 4, 5-trifluorophenyl)piperidin-3-amine	KI	1.6 nM
3-{6-[(3R,4S)-3-amino-4-(2,4,5-trifluorophenyl)pyrrolidin-1-yl]pyrimidin-4-yl}benzoic acid	KI	1.8 nM
2-{[2-(3-aminopiperidin-1-yl)-5-methyl-4,6-dioxo-1H,4H,5H,6H-pyrrolo[3,4-d]imidazol-1-yl]methyl}benzonitrile	KI	2 nM
(3R,4S)-1-[4-(3-methanesulfonylphenyl)-1,3,5-triazin-2-yl]-4-(2,4,5-trifluorophenyl)pyrrolidin-3-amine	KI	2.1 nM
(R)-1-(6-((3R,4R)-3-Amino-4-(2,4,5-trifluorophenyl)piperidin-1-yl)pyrimidin-4-yl)pyrrolidin-3-ol	KI	2.3 nM
ABT-279 analogue	KI	3 nM
(3R,4S)-1-{6-[3-(morpholine-4-sulfonyl)phenyl]pyrimidin-4-yl}-4-(2,4,5-trifluorophenyl)pyrrolidin-3-amine	KI	3.2 nM
Racemic mixture	KI	3.2 nM
(3R,4S)-1-[6-(3-methanesulfonylphenyl)pyrimidin-4-yl]-4-(2,4,5-trifluorophenyl)pyrrolidin-3-amine	KI	3.4 nM
(1S,6R)-3-(3-carbamoylphenoxymethyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	3.6 nM
3-{2-[(4R,5R)-5-amino-2-oxo-4-(2,4,5-trifluorophenyl)piperidin-1-yl]ethyl}benzoic acid	KI	3.8 nM
6-{[4-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)cyclohexyl]oxy}pyridine-3-carbonitrile	KI	4 nM
(4R,5R)-5-amino-1-[2-(3-methanesulfonylphenyl)ethyl]-4-(2,4,5-trifluorophenyl)piperidin-2-one	KI	4 nM
(3R,4R)-1-(6-(3-(methylsulfonyl)phenyl)pyrimidin-4-yl)-4-(2,4,5-trifluorophenyl)-piperidin-3-amine	KI	4 nM
(1S,6R)-3-[(3-carbamoylphenyl)carbamoyl]-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	4.7 nM
6-{[4-({2-[(2S,5R)-2-cyano-5-ethynylpyrrolidin-1-yl]-2-oxoethyl}amino)cyclohexyl]oxy}pyridine-3-carbonitrile	KI	5 nM
(1S,6R)-3-{[(3-carbamoylphenyl)amino]methyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	6 nM
C5-substituted pyrrolidine 16	KI	8 nM
(2S)-1-[2-(tert-butylamino)acetyl]pyrrolidine-2-carbonitrile	KI	10 nM
(2S)-1-[2-(cyclopentylamino)acetyl]pyrrolidine-2-carbonitrile	KI	11 nM
(1S,6R)-3-(1,2,3,4-tetrahydroisoquinolin-2-ylmethyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-aminium; 2,2,2-trifluoroacetate	KI	12 nM
N-{4-[(2S,3S)-3-amino-4-[(3S)-3-fluoropyrrolidin-1-yl]-4-oxobutan-2-yl]cyclohexyl}-N-methylacetamide	IC50	16 nM
(2S,3S)-3-{4-[cyclopropane(methyl)amido]cyclohexyl}-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxobutan-2-aminium	IC50	21 nM
(2S,5R)-1-[2-(cyclopentylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile	KI	22 nM
(2S,3S)-3-{4-[(3-fluorobenzene)(methyl)amido]cyclohexyl}-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxobutan-2-aminium	IC50	22 nM
(R)-40	IC50	23.5 nM
(1S,2S)-1-(dimethylcarbamoyl)-1-{4-[(3-fluorobenzene)(methyl)amido]cyclohexyl}-3-[(3S)-3-fluoropyrrolidin-1-yl]-3-oxopropan-2-aminium	IC50	24 nM
(2S,5R)-1-[2-(tert-butylamino)acetyl]-5-ethynylpyrrolidine-2-carbonitrile	KI	25 nM
2-(3-aminopiperidin-1-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}-1H,4H,9H-naphtho[2,3-d]imidazole-4,9-dione	KI	25 nM
(2S,3S)-1-[(3S)-3-fluoropyrrolidin-1-yl]-3-{4-[(4-methoxybenzene)(methyl)amido]cyclohexyl}-1-oxobutan-2-aminium	IC50	27 nM
(1S,2S)-1-(dimethylcarbamoyl)-3-[(3S)-3-fluoropyrrolidin-1-yl]-1-[4-(N-methylacetamido)cyclohexyl]-3-oxopropan-2-aminium	IC50	29 nM
(R)-43	IC50	36.2 nM
(S)-43	IC50	36.9 nM
N-{4-[(1S)-1-amino-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethyl]cyclohexyl}-2,4-difluorobenzene-1-sulfonamide	IC50	48 nM
(1S)-1-{4-[(2,4-difluorobenzene)sulfonamido]cyclohexyl}-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethan-1-aminium	IC50	48 nM
(2S)-1-{2-[(3-hydroxyadamantan-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile	IC50	51 nM
(2S,5R)-5-ethynyl-1-{2-[(3-hydroxyadamantan-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile	KI	62 nM
(2S,3S)-1-[(3S)-3-fluoropyrrolidin-1-yl]-3-{4-[(4-methoxybenzene)amido]cyclohexyl}-1-oxobutan-2-aminium	IC50	74 nM
(2S,3S)-3-{4-[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)phenyl]phenyl}-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxobutan-2-aminium; 2,2,2-trifluoroacetate	IC50	96 nM
(S)-40	IC50	108 nM
(2S,3S)-3-{4-[4-(ethoxycarbonyl)phenyl]phenyl}-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxobutan-2-aminium; 2,2,2-trifluoroacetate	IC50	120 nM
SLRFLYEG	KI	147 nM
oxadiazole based amide	IC50	160 nM
SLRFLYDG	KI	167 nM
SLRFLYAG	KI	200 nM
(2S,3S)-1-[(3S)-3-fluoropyrrolidin-1-yl]-3-[4-(3-methanesulfonamidophenyl)phenyl]-1-oxobutan-2-aminium; 2,2,2-trifluoroacetate	IC50	250 nM

ChEMBL bioactivities

593 potent at pChembl≥5 of 894 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	IC50	0.12	nM	VILDAGLIPTIN
9.72	Ki	0.19	nM	CHEMBL1215376
9.55	Ki	0.28	nM	CHEMBL1215374
9.52	Ki	0.3	nM	CHEMBL2441845
9.52	Ki	0.3	nM	CHEMBL1215375
9.51	IC50	0.31	nM	CHEMBL2063040
9.39	Ki	0.41	nM	CHEMBL67089
9.30	Ki	0.5	nM	CHEMBL2441839
9.28	Ki	0.53	nM	CHEMBL63860
9.26	Ki	0.55	nM	CHEMBL1215236
9.22	Ki	0.6	nM	CHEMBL1215167
9.12	Ki	0.76	nM	TALABOSTAT
9.10	Ki	0.8	nM	CHEMBL2441955
9.08	Ki	0.83	nM	CHEMBL1215087
9.07	Ki	0.86	nM	CHEMBL1215299
9.05	Ki	0.9	nM	CHEMBL2441954
9.05	Ki	0.9	nM	CHEMBL2441844
9.05	Ki	0.9	nM	CHEMBL1215089
9.05	Ki	0.9	nM	CHEMBL1215233
9.03	Ki	0.94	nM	CHEMBL1215164
9.00	IC50	1	nM	CHEMBL5425473
9.00	Ki	1	nM	CHEMBL1214942
8.92	Ki	1.2	nM	CHEMBL2441831
8.89	Ki	1.3	nM	CHEMBL2441846
8.89	Ki	1.3	nM	CHEMBL2441829
8.89	Ki	1.3	nM	CHEMBL1215017
8.85	Ki	1.4	nM	CHEMBL1214877
8.82	Ki	1.5	nM	CHEMBL1214944
8.74	Ki	1.8	nM	CHEMBL2441953
8.72	Ki	1.9	nM	CHEMBL2441836
8.72	Ki	1.9	nM	CHEMBL1215016
8.72	Ki	1.9	nM	CHEMBL1215302
8.70	IC50	2	nM	CHEMBL195189
8.70	IC50	2	nM	TALABOSTAT
8.70	Ki	2	nM	CHEMBL1215088
8.68	IC50	2.1	nM	CHEMBL2063033
8.68	Ki	2.1	nM	CHEMBL1215448
8.66	IC50	2.2	nM	TALABOSTAT
8.66	Ki	2.2	nM	CHEMBL1214943
8.66	Ki	2.2	nM	CHEMBL1215018
8.64	Ki	2.3	nM	CHEMBL2441837
8.64	Ki	2.3	nM	CHEMBL2441830
8.60	Ki	2.5	nM	CHEMBL1215163
8.60	Ki	2.5	nM	CHEMBL1215166
8.59	Ki	2.6	nM	CHEMBL494497
8.55	IC50	2.8	nM	CHEMBL63860
8.55	Ki	2.8	nM	CHEMBL2441847
8.54	Ki	2.9	nM	CHEMBL2441841
8.52	Ki	3	nM	CHEMBL94278
8.52	IC50	3	nM	CHEMBL5402430

PubChem BioAssay actives

557 with measured affinity, of 1969 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carbonitrile	1781440: Inhibition of human recombinant DPP9 using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition and measured for 20 mins by fluorescence based microplate reader assay	ic50	0.0001	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(2-pyridin-2-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0002	uM
3-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]propanoic acid	778686: Inhibition of DPP9 (unknown origin)	ki	0.0003	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(2-pyridin-3-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0003	uM
1-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-2-[(6-methyl-2-pyridinyl)methylamino]ethanone	499234: Inhibition of human DPP9	ki	0.0003	uM
[(2R,4S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]-4-hydroxypyrrolidin-2-yl]boronic acid	675170: Inhibition of human DPP9 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins	ic50	0.0003	uM
[(2R)-1-(2-aminoacetyl)pyrrolidin-2-yl]boronic acid	390966: Inhibition of human recombinant DPP9 expressed in HEK293T cells	ki	0.0004	uM
[(2R)-1-[(2S)-2-aminopropanoyl]pyrrolidin-2-yl]boronic acid	390966: Inhibition of human recombinant DPP9 expressed in HEK293T cells	ki	0.0005	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-[[(2S)-oxolan-2-yl]methyl]-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0005	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(pyridin-3-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0006	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(2-pyridin-2-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0006	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-(2-oxo-2-piperidin-1-ylethyl)-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0008	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-(4-methylsulfonylpiperazin-1-yl)methanone	499234: Inhibition of human DPP9	ki	0.0008	uM
[(2R)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid	390966: Inhibition of human recombinant DPP9 expressed in HEK293T cells	ki	0.0008	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-(2-oxo-2-pyrrolidin-1-ylethyl)-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0009	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(2,5-dimethylpyrazol-3-yl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0009	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-(4,4-dimethyl-1,3-oxazolidin-3-yl)methanone	499234: Inhibition of human DPP9	ki	0.0009	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(2-ethylpyrazol-3-yl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0009	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0009	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]acetic acid	778686: Inhibition of DPP9 (unknown origin)	ki	0.0009	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-pyrrolidin-1-ylmethanone	499234: Inhibition of human DPP9	ki	0.0010	uM
(2S)-2-amino-1-(1,3-dihydroisoindol-2-yl)-2-(4-hydroxycyclohexyl)ethanone	2015042: Inhibition of DPP9 (unknown origin)	ic50	0.0010	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-(1-methylpyrazol-3-yl)-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0012	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(4-methoxyphenyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0013	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-diethylacetamide	778686: Inhibition of DPP9 (unknown origin)	ki	0.0013	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methanone	499234: Inhibition of human DPP9	ki	0.0013	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,N-diethyl-7-methylimidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0014	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(oxan-4-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0015	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N-methyl-N-propylacetamide	778686: Inhibition of DPP9 (unknown origin)	ki	0.0018	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyethyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0019	uM
4-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carbonyl]piperazin-2-one	499234: Inhibition of human DPP9	ki	0.0019	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(4-pyridin-3-yl-1,3-thiazol-2-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0019	uM
[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid	255020: Inhibitory concentration against human dipeptidylpeptidase 9 using FP-TAMRA incubated for 30 min	ic50	0.0020	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-N,7-dimethyl-N-(2-methylsulfonylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0020	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(2-pyridin-4-ylethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0021	uM
[(2R,4S)-4-hydroxy-1-[(2S)-pyrrolidine-2-carbonyl]pyrrolidin-2-yl]boronic acid	675170: Inhibition of human DPP9 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins	ic50	0.0021	uM
[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl]-morpholin-4-ylmethanone	499234: Inhibition of human DPP9	ki	0.0022	uM
N-[(3S)-1-[6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carbonyl]pyrrolidin-3-yl]methanesulfonamide	499234: Inhibition of human DPP9	ki	0.0022	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyphenyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0023	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-[(2S)-1-methoxypropan-2-yl]-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0023	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(1,3-oxazol-2-ylmethyl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0025	uM
6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methyl-N-(1,2-oxazol-3-yl)imidazo[1,2-a]pyrimidine-2-carboxamide	499234: Inhibition of human DPP9	ki	0.0025	uM
(4S)-4-amino-5-[(2R)-2-boronopyrrolidin-1-yl]-5-oxopentanoic acid	390966: Inhibition of human recombinant DPP9 expressed in HEK293T cells	ki	0.0026	uM
3-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-diethylpropanamide	778686: Inhibition of DPP9 (unknown origin)	ki	0.0028	uM
3-(aminomethyl)-6-[[(2S)-1-cyclopropylsulfonylpyrrolidin-2-yl]methyl]-4-(2,4-dichlorophenyl)-2-methyl-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0029	uM
tert-butyl N-[3-[[2-(5,6-difluoro-1,3-dihydroisoindol-2-yl)-2-oxoethyl]amino]-1-adamantyl]carbamate	2015034: Inhibition of N-terminal human recombinant DPP9 expressed in Sf9 insect cells using Ala-Pro-paranitroanilide as substrate incubated for 15 mins by fluorescence based analysis	ic50	0.0030	uM
(2S)-1-[(2S)-2-amino-2-cyclopentylacetyl]pyrrolidine-2-carbonitrile	1796928: DPPIV Inhibition Assay from Article 10.1021/jm060777o: “Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.”	ki	0.0030	uM
3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-6-[[(2R)-oxolan-2-yl]methyl]-7H-pyrrolo[3,4-b]pyridin-5-one	778686: Inhibition of DPP9 (unknown origin)	ki	0.0031	uM
2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-dimethylacetamide	778686: Inhibition of DPP9 (unknown origin)	ki	0.0032	uM
ethyl 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylate	499234: Inhibition of human DPP9	ki	0.0033	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
Estradiol	affects cotreatment, increases expression, affects expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
bisphenol S	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
chloroacetaldehyde	increases expression	1
daidzein	affects cotreatment, decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
daidzin	affects cotreatment, decreases expression	1
arsenite	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
genistin	decreases expression, affects cotreatment	1
glycylproline 4-nitroanilide	affects cotreatment, decreases activity, decreases cleavage	1
alanylproline-4-nitroanilide	affects cotreatment, decreases activity, decreases cleavage	1
glycitein	affects cotreatment, decreases expression	1
glycitin	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
UAMC00132	affects cotreatment, decreases activity, decreases cleavage	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	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1

ChEMBL screening assays

160 unique, capped per target: 154 binding, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3873291	Binding	Inhibition of full length recombinant human DPP-8/9 expressed in HEK293 cells at 10 uM incubated for 1 hr	Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents. — Eur J Med Chem
CHEMBL4683607	ADMET	Inhibition of recombinant human DPP8/9 expressed in Rosetta cells at 10 uM using Gly-Pro-p-nitroanilide as substrate incubated for 1 hr relative to control	The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION