DPEP3

Summary

DPEP3 (dipeptidase 3, HGNC:23029) is a protein-coding gene on chromosome 16q22.1, encoding Dipeptidase 3 (Q9H4B8). Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine, leukotriene D4 and the beta-lactam antibiotic imipenem.

This gene encodes a membrane-bound glycoprotein from the family of dipeptidases involved in hydrolytic metabolism of various dipeptides, including penem and carbapenem beta-lactam antibiotics. This gene is located on chromosome 16 in a cluster with another member of this family. Alternatively spliced transcript variants that encode different isoforms have been found for this gene.

Source: NCBI Gene 64180 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 85 total
• GTEx eGene: eQTL in 6 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.10 (unconstrained)
• MANE Select transcript: NM_001370198
• Notable: 85 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23029
Approved symbol	DPEP3
Name	dipeptidase 3
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000141096
Ensembl biotype	protein_coding
OMIM	609926
Entrez	64180

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000268793

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

ENST00000268793, ENST00000574342, ENST00000672962, ENST00000876631, ENST00001078873, ENST00001132725

RefSeq mRNA: 2 — MANE Select: NM_001370198 NM_001129758, NM_001370198

CCDS: CCDS10856

Canonical transcript exons

ENST00000268793 — 10 exons

Exon	Start	End
ENSE00000946577	67978267	67978408
ENSE00000946578	67977938	67978007
ENSE00000946581	67976700	67976775
ENSE00000946582	67976093	67976228
ENSE00001294460	67975663	67976001
ENSE00001322074	67980094	67980499
ENSE00001598520	67978497	67978626
ENSE00001664599	67979639	67979765
ENSE00001679349	67977653	67977829
ENSE00001703908	67977270	67977354

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 95.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4872 / max 284.0760, expressed in 75 samples.

Highest expression (Bgee): testis, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, sperm, male germ cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DPEP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	5.2e-13	-0.21	16:67964017:T:C
Thyroid	eqtl	5.9e-04	-0.67	16:67182085:T:A
Lung	eqtl	2.1e-03	+0.64	16:67970312:A:G
Spleen	sqtl	3.0e-03	-1.24	16:68361925:G:C
Testis	sqtl	1.4e-02	-1.28	16:68686421:C:T
Muscle Skeletal	eqtl	1.7e-02	+0.28	16:67145070:C:T
Adipose Subcutaneous	eqtl	2.8e-02	+0.54	16:68005937:T:A
Adipose Visceral Omentum	eqtl	4.2e-02	-1.02	16:68462120:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
157842	0.3069	50
157841	0.1647	54
157840	0.0156	8

Top tissues by expression

showing 100 of 254 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	95.11	gold quality
left testis	UBERON:0004533	93.80	gold quality
testis	UBERON:0000473	91.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.15	gold quality
sperm	CL:0000019	77.02	silver quality
male germ cell	CL:0000015	76.44	silver quality
blood	UBERON:0000178	75.49	gold quality
adult organism	UBERON:0007023	74.46	gold quality
diaphragm	UBERON:0001103	70.45	gold quality
granulocyte	CL:0000094	70.05	gold quality
triceps brachii	UBERON:0001509	69.41	gold quality
tendon of biceps brachii	UBERON:0008188	65.59	gold quality
buccal mucosa cell	CL:0002336	65.46	gold quality
vastus lateralis	UBERON:0001379	65.26	gold quality
gluteal muscle	UBERON:0002000	64.94	gold quality
spleen	UBERON:0002106	64.80	gold quality
biceps brachii	UBERON:0001507	64.64	gold quality
quadriceps femoris	UBERON:0001377	64.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	61.20	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.84	gold quality
bone marrow	UBERON:0002371	60.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	59.15	gold quality
skeletal muscle tissue	UBERON:0001134	59.10	gold quality
bone marrow cell	CL:0002092	58.42	gold quality
decidua	UBERON:0002450	57.86	gold quality
superficial temporal artery	UBERON:0001614	57.67	gold quality
leukocyte	CL:0000738	57.45	gold quality
myocardium	UBERON:0002349	57.19	gold quality
deltoid	UBERON:0001476	56.77	gold quality
monocyte	CL:0000576	56.68	gold quality
trabecular bone tissue	UBERON:0002483	56.63	gold quality
mononuclear cell	CL:0000842	56.62	gold quality
lateral globus pallidus	UBERON:0002476	55.88	gold quality
nasal cavity epithelium	UBERON:0005384	55.62	gold quality
esophagus squamous epithelium	UBERON:0006920	55.38	gold quality
oral cavity	UBERON:0000167	55.24	gold quality
heart right ventricle	UBERON:0002080	55.22	gold quality
epithelium of esophagus	UBERON:0001976	55.18	gold quality
cartilage tissue	UBERON:0002418	55.05	gold quality
pharyngeal mucosa	UBERON:0000355	54.98	gold quality
globus pallidus	UBERON:0001875	54.95	gold quality
saphenous vein	UBERON:0007318	54.87	gold quality
medial globus pallidus	UBERON:0002477	54.86	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	54.81	gold quality
pons	UBERON:0000988	54.75	gold quality
inferior olivary complex	UBERON:0002127	54.69	gold quality
pigmented layer of retina	UBERON:0001782	53.89	gold quality
substantia nigra pars reticulata	UBERON:0001966	53.65	gold quality
lymph node	UBERON:0000029	53.51	gold quality
substantia nigra pars compacta	UBERON:0001965	53.47	gold quality
body of tongue	UBERON:0011876	53.20	gold quality
superior surface of tongue	UBERON:0007371	53.15	gold quality
duodenum	UBERON:0002114	53.01	gold quality
subthalamic nucleus	UBERON:0001906	52.97	gold quality
tongue	UBERON:0001723	52.91	gold quality
parotid gland	UBERON:0001831	52.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.85	gold quality
medulla oblongata	UBERON:0001896	52.79	gold quality
trigeminal ganglion	UBERON:0001675	52.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	52.44	gold quality
thymus	UBERON:0002370	52.41	gold quality
small intestine	UBERON:0002108	52.34	gold quality
layer of synovial tissue	UBERON:0007616	52.23	gold quality
squamous epithelium	UBERON:0006914	51.98	gold quality
pericardium	UBERON:0002407	51.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	51.53	gold quality
synovial joint	UBERON:0002217	51.49	gold quality
mucosa of urinary bladder	UBERON:0001259	51.46	gold quality
nipple	UBERON:0002030	51.42	gold quality
penis	UBERON:0000989	51.39	gold quality
placenta	UBERON:0001987	51.33	silver quality
seminal vesicle	UBERON:0000998	51.22	gold quality
pylorus	UBERON:0001166	51.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.22	gold quality
renal medulla	UBERON:0000362	51.21	gold quality
ventral tegmental area	UBERON:0002691	51.13	gold quality
trachea	UBERON:0003126	51.09	gold quality
superior vestibular nucleus	UBERON:0007227	50.99	gold quality
cerebellar vermis	UBERON:0004720	50.81	gold quality
vena cava	UBERON:0004087	50.63	gold quality
pancreatic ductal cell	CL:0002079	50.60	silver quality
right lung	UBERON:0002167	50.43	gold quality
inferior vagus X ganglion	UBERON:0005363	50.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	50.08	gold quality
caecum	UBERON:0001153	49.97	gold quality
cardia of stomach	UBERON:0001162	49.84	gold quality
mammalian vulva	UBERON:0000997	49.79	gold quality
oocyte	CL:0000023	49.68	gold quality
epithelial cell of pancreas	CL:0000083	49.57	gold quality
urethra	UBERON:0000057	49.57	gold quality
middle temporal gyrus	UBERON:0002771	49.33	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
dorsal root ganglion	UBERON:0000044	49.18	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
orbitofrontal cortex	UBERON:0004167	49.11	gold quality
oviduct epithelium	UBERON:0004804	49.04	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	1242.67
E-ANND-3	no	0.95

HPA expression

RNA tissue specificity: Tissue enriched

59 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	34.8	high
Spleen	tissue	1.9	not detected
Bone marrow	tissue	1.6	not detected
Periaqueductal gray	tissue	1.5
Basal ganglia	tissue	1.2	not detected
Hippocampal formation	tissue	0.9
Septum	tissue	0.9
Cerebral cortex	tissue	0.8	not detected
Putamen	tissue	0.8
Small intestine	tissue	0.8	not detected
Entorhinal cortex	tissue	0.8
Ventral forebrain	tissue	0.8
Occipital cortex	tissue	0.8
Insular cortex	tissue	0.8
Motor cortex	tissue	0.7
Amygdala	tissue	0.7
Choroid plexus	tissue	0.7
Retrosplenial and cingulate cortex	tissue	0.7
Somatosensory cortex	tissue	0.7
Retrosplenial cortex	tissue	0.7
Temporal cortex	tissue	0.7
Prefrontal cortex	tissue	0.6
Pons	tissue	0.5
Tongue	tissue	0.5
Hypothalamus	tissue	0.5
Olfactory bulb	tissue	0.5
Lymph node	tissue	0.4	not detected
Adipose tissue	tissue	0.4	not detected
Thalamus	tissue	0.4
Cerebellum	tissue	0.4	not detected
Duodenum	tissue	0.4	not detected
Corpus callosum	tissue	0.4
Stomach 1	tissue	0.3	not detected
Midbrain	tissue	0.3
Medulla oblongata	tissue	0.3
Substantia nigra	tissue	0.3
Spinal cord	tissue	0.3
Seminal vesicle	tissue	0.2	not detected
Colon	tissue	0.2	not detected
Urinary bladder	tissue	0.2	not detected
Nucleus accumbens	tissue	0.2
Superior colliculi	tissue	0.2
Lung	tissue	0.2	not detected
Tonsil	tissue	0.2	not detected
Appendix	tissue	0.2	not detected
Heart muscle	tissue	0.1	not detected
Ovary	tissue	0.1	not detected
Rectum	tissue	0.1	not detected
Skeletal muscle	tissue	0.1	not detected
Pancreas	tissue	0.1	not detected
Placenta	tissue	0.1	not detected
Liver	tissue	0.1	not detected
Gallbladder	tissue	0.1	not detected
Locus coeruleus	tissue	0.1
Hippocampus	tissue	0.1	not detected
Adrenal gland	tissue	0.1	not detected
Thymus	tissue	0.1
Postcentral gyrus	tissue	0.1
Fallopian tube	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Ventral hippocampus (0.9), Dorsal hippocampus (0.8), Lateral funiculus (white matter) (0.6), Subiculum (0.5), Habenula (0.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DPEP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6805-5P	95.79	64.86	670

Functional genomics

gnomAD constraint: pLI 8.88e-13, LOEUF 1.1, missense Z 1.48 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000268793 — one region, missense o/e 0.88.

Literature-anchored findings (GeneRIF, showing 1)

• This paper describes differences in substrate specificity and tissue distribution of membrane-bound dipeptidase 3 from mouse in comparison to other mouse members of this family. (PMID:12738806)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dpep3	ENSMUSG00000031898
rattus_norvegicus	Dpep3	ENSRNOG00000019757
drosophila_melanogaster	CG6154	FBGN0039420
drosophila_melanogaster	CG44837	FBGN0266100

Paralogs (2): DPEP1 (ENSG00000015413), DPEP2 (ENSG00000167261)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919104) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
oligozoospermia	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Coccidioides posadasii C735 delta SOWgp	C5PCN6	100.0%	Diamond
Coccidioides posadasii str. Silveira	E9CV02	100.0%	Diamond
Trichophyton benhamiae CBS 112371	D4B2N2	99.5%	Diamond
Trichophyton verrucosum HKI 0517	D4DEJ7	99.5%	Diamond
Ovis aries	P43477	97.3%	Diamond
Bos taurus	Q3SZM7	97.3%	Diamond
Nannizzia gypsea CBS 118893	E5R2Q7	94.2%	Diamond
Macaca fascicularis	Q4R7M2	93.9%	Diamond
Sus scrofa	P22412	88.1%	Diamond
Microsporum canis CBS 113480	C5FK77	86.5%	Diamond
Oryctolagus cuniculus	P31429	82.2%	Diamond
Uncinocarpus reesii 1704	C4JQN7	78.6%	Diamond
Talaromyces stipitatus ATCC 10500	B8LWT1	59.3%	Diamond
Fusarium vanettenii 77-13-4	C7ZIE1	59.2%	Diamond
Schizosaccharomyces pombe 972h-	O59832	54.7%	Diamond
Aspergillus oryzae RIB40	Q2UPB0	50.9%	Diamond
Aspergillus fumigatus Af293	Q4WMJ8	50.9%	Diamond
Aspergillus terreus NIH2624	Q0CS61	50.6%	Diamond
Plenodomus lingam	Q6Q886	50.3%	Diamond
Clonostachys rogersoniana	A0A1U9YI27	50.1%	Diamond
Claviceps purpurea 20.1	M1VV65	48.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DPEP2NB	protein-coding	100131303
DPEP2	protein-coding	64174
LCAT	protein-coding	3931
SLC12A4	protein-coding	6560
PSMB10	protein-coding	5699
CTRL	protein-coding	1506
PSKH1	protein-coding	5681
NRN1L	protein-coding	123904

Protein

Protein identifiers

Dipeptidase 3 — Q9H4B8 (reviewed: Q9H4B8)

All UniProt accessions (2): A0A5F9ZHB4, Q9H4B8

UniProt curated annotations — full annotation on UniProt →

Function. Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine, leukotriene D4 and the beta-lactam antibiotic imipenem. The absence of activity may be due to the inability of asparagine (instead of aspartate found in DPEP1/2) at position 359 to function as the acid/base catalyst and activate the nucleophilic water/hydroxide. A tyrosine (instead of histidine) at position 269 reduces affinity for the beta zinc and may cause substrate steric hindrance.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with TEX101; co-localized on the cell surface of spermatocytes, spermatids, and testicular spermatozoa, co-localized only in cytoplasmic droplets of caput and corpus epididymal sperm.

Subcellular location. Membrane.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.

RefSeq proteins (2): NP_001123230, NP_001357127* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000180	Dipep_AS	Active_site
IPR008257	Pept_M19	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF01244

UniProt features (50 total): helix 21, strand 14, turn 4, disulfide bond 3, sequence conflict 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6VGO	Crystal Structure of Human Dipeptidase 3	X-RAY DIFFRACTION	1.82
6VGR	Crystal Structure of Human Dipeptidase 3 in Complex with Fab of SC-003	X-RAY DIFFRACTION	2.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4B8-F1	84.15	0.70

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 6VGR, TAMRINTAMAB

Human Protein Atlas

Protein class: Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated serine	463

Disulfide bonds (3)

Type	Positions
Disulfide bond	146–225, 297–329
Interchain	434

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	334

Mutagenesis-validated functional residues (1)

Position	Phenotype
196	loss of zinc binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 92 (showing top): chr16q22, GOCC_SECRETORY_GRANULE, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_FATTY_ACID_DERIVATIVE_METABOLIC_PROCESS, GOBP_LEUKOTRIENE_METABOLIC_PROCESS, GOCC_SECRETORY_VESICLE, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS

GO Biological Process (2): proteolysis (GO:0006508), leukotriene D4 catabolic process (GO:1901749)

GO Molecular Function (3): dipeptidase activity (GO:0016805), peptidase activity (GO:0008233), metallodipeptidase activity (GO:0070573)

GO Cellular Component (4): acrosomal vesicle (GO:0001669), plasma membrane (GO:0005886), membrane (GO:0016020), side of membrane (GO:0098552)

GO top-level categories

14 GO namespaces:

Category	Terms
membrane	2
cellular anatomical structure	2
protein metabolic process	1
leukotriene catabolic process	1
sulfur compound catabolic process	1
icosanoid catabolic process	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
metalloexopeptidase activity	1
dipeptidase activity	1
secretory granule	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

showing 15 of 868 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPEP3	TEX101	Q9BY14	547
DPEP3	CNDP2	Q96KP4	439
DPEP3	SMIM12	Q96EX1	396
DPEP3	SHISA4	Q96DD7	386
DPEP3	SPACA4	Q8TDM5	377
DPEP3	BEND7	Q8N7W2	371
DPEP3	CTSC	P53634	368
DPEP3	ABI3BP	Q7Z7G0	365
DPEP3	XPNPEP2	O43895	364
DPEP3	CHN2	P52757	362
DPEP3	LRRC40	Q9H9A6	362
DPEP3	A0A2R8YEI5	A0A2R8YEI5	362
DPEP3	MNMIP1	A4FU49	357
DPEP3	LY6K	Q17RY6	348
DPEP3	AAMDC	Q9H7C9	340

IntAct

Human interaction partners of DPEP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
HSPA5	association	0.530	2
TEX101	proximity	0.420	4
PDIA6	physical association	0.400	1

BioGRID (13 interactions; top human partners by supporting records): DPEP2 (Affinity Capture-MS; 3 records), TEX101 (Affinity Capture-MS; 3 records), CANX (Affinity Capture-MS; 2 records), HSPA5 (Affinity Capture-MS; 2 records), CHD4 (Affinity Capture-MS), EGFR (Affinity Capture-MS), LINC00839 (Protein-RNA)

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CYSLTR2	ligand	Signaling by Lipoxin/Leukotriene
CYSLTR1	ligand	Signaling by Lipoxin/Leukotriene

Disease & clinical

Genetic variants

Variant evidence for DPEP3: 85 ClinVar records (0 pathogenic / likely pathogenic); 23 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	4
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 795):

Position(s)	Effect	Δscore	Sites
16:67976091–67976092	donor_loss	1.0000	3
16:67977936–67977937	donor_loss	1.0000	4
16:67978008–67978009	acceptor_loss	1.0000	4
16:67978266	donor_loss	1.0000
16:67978409–67978410	acceptor_loss	1.0000	5
16:67976002–67976003	acceptor_loss	0.9900	2
16:67976091	donor_loss	0.9900
16:67977268–67977269	donor_loss	0.9900	3
16:67977355–67977356	acceptor_loss	0.9900	5
16:67977651–67977652	donor_loss	0.9900	5

AlphaMissense

427 missense substitutions predicted likely pathogenic (of 3,133 scored), across 150 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
W229	7	0.888	0.975
W140	7	0.842	0.972
D266	7	0.805	0.843
W388	7	0.804	0.906
N400	7	0.800	0.914
E257	7	0.773	0.845
C297	7	0.765	0.814
C225	7	0.759	0.829
C146	7	0.719	0.800
D95	7	0.670	0.806
D162	7	0.640	0.729
G215	6	0.826	0.936
C329	6	0.748	0.822
M88	6	0.745	0.821
H341	6	0.721	0.801
C168	6	0.697	0.871
F139	5	0.906	0.939
F250	5	0.832	0.910
G355	5	0.817	0.875
G262	5	0.790	0.919

HPA cancer prognostics

RNA cancer specificity: Group enriched (Ovary Serous Cystadenocarcinoma, Skin Cutaneous Melanoma, Testicular Germ Cell Tumor)

Disease associations

OMIM: gene MIM:609926 | disease phenotypes:

GWAS associations

23 associations:

Study	Trait	p-value
GCST008084_142	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-99
GCST008075_69	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5e-81
GCST008085_169	HDL cholesterol levels in current drinkers	7e-54
GCST008084_11	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-50
GCST008075_217	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4e-39
GCST008070_58	HDL cholesterol levels	2e-35
GCST008084_110	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4e-24
GCST008075_8	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3e-23
GCST008085_35	HDL cholesterol levels in current drinkers	3e-23
GCST008084_95	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-19
GCST008070_79	HDL cholesterol levels	1e-17
GCST008085_87	HDL cholesterol levels in current drinkers	5e-17
GCST008075_44	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-16
GCST010002_165	Refractive error	2e-14
GCST008085_75	HDL cholesterol levels in current drinkers	3e-14
GCST008084_138	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3e-11
GCST008075_60	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1e-10
GCST008070_15	HDL cholesterol levels	4e-10
GCST002539_44	Schizophrenia	2e-8
GCST006803_78	Schizophrenia	4e-8
GCST008085_161	HDL cholesterol levels in current drinkers	6e-8
GCST008070_48	HDL cholesterol levels	4e-6
GCST008087_136	Triglyceride levels in current drinkers	9e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, increases expression	2
testosterone enanthate	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
cetrorelix	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects binding, increases expression	1
Ozone	affects expression, increases abundance	1
Valproic Acid	increases methylation	1
Desogestrel	affects cotreatment, decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.