EPX

Summary

EPX (eosinophil peroxidase, HGNC:3423) is a protein-coding gene on chromosome 17q22, encoding Eosinophil peroxidase (P11678). Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils.

This gene is a member of the peroxidase gene family and is expressed in eosinophils. The encoded preproprotein is proteolytically processed into covalently attached heavy and light chains to form the mature enzyme, which functions as an oxidant. The enzyme is released at sites of parasitic infection or allergen stimulation to mediate lysis of protozoa or parasitic worms. The gene is found in a gene cluster with other peroxidase genes on chromosome 17. Mutations in this gene result in eosinophil peroxidase deficiency.

Source: NCBI Gene 8288 — RefSeq curated summary.

At a glance

• Gene–disease (curated): eosinophil peroxidase deficiency (Limited, GenCC)
• Clinical variants (ClinVar): 162 total
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_000502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3423
Approved symbol	EPX
Name	eosinophil peroxidase
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	EPO, EPP, EPX-PEN
Ensembl gene	ENSG00000121053
Ensembl biotype	protein_coding
OMIM	131399
Entrez	8288

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000225371

RefSeq mRNA: 1 — MANE Select: NM_000502 NM_000502

CCDS: CCDS11602

Canonical transcript exons

ENST00000225371 — 13 exons

Exon	Start	End
ENSE00000739111	58192726	58192922
ENSE00000739112	58193038	58193131
ENSE00000739113	58193371	58193546
ENSE00000739114	58193714	58193831
ENSE00000739115	58193963	58194092
ENSE00000739116	58194964	58195170
ENSE00000739117	58196939	58197257
ENSE00000739118	58199040	58199200
ENSE00000739119	58199539	58199794
ENSE00000739153	58203081	58203318
ENSE00000739157	58204222	58204434
ENSE00001693468	58204736	58205174
ENSE00002512830	58200225	58200395

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 99.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5876 / max 284.1782, expressed in 36 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161897	0.5776	32
208278	0.0100	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	99.00	gold quality
trabecular bone tissue	UBERON:0002483	94.30	gold quality
bone marrow	UBERON:0002371	85.72	gold quality
bone element	UBERON:0001474	84.76	gold quality
bone marrow cell	CL:0002092	77.00	gold quality
pancreatic ductal cell	CL:0002079	66.45	silver quality
Brodmann (1909) area 10	UBERON:0013541	66.10	gold quality
endometrium epithelium	UBERON:0004811	66.03	gold quality
cerebellar hemisphere	UBERON:0002245	63.13	gold quality
cerebellar cortex	UBERON:0002129	62.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.59	gold quality
diaphragm	UBERON:0001103	62.43	gold quality
endothelial cell	CL:0000115	61.81	gold quality
cerebellum	UBERON:0002037	61.43	gold quality
cortical plate	UBERON:0005343	61.05	gold quality
ileal mucosa	UBERON:0000331	60.48	silver quality
right uterine tube	UBERON:0001302	59.00	gold quality
prefrontal cortex	UBERON:0000451	56.08	gold quality
spleen	UBERON:0002106	55.59	gold quality
frontal pole	UBERON:0002795	55.25	gold quality
lateral nuclear group of thalamus	UBERON:0002736	55.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	54.93	gold quality
right frontal lobe	UBERON:0002810	54.60	gold quality
quadriceps femoris	UBERON:0001377	54.06	gold quality
colonic epithelium	UBERON:0000397	53.99	silver quality
ganglionic eminence	UBERON:0004023	53.79	silver quality
blood	UBERON:0000178	53.78	gold quality
frontal cortex	UBERON:0001870	53.59	gold quality
metanephric glomerulus	UBERON:0004736	53.57	gold quality
cerebellar vermis	UBERON:0004720	53.48	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	32551.67
E-MTAB-9067	yes	12.87
E-CURD-112	yes	9.72
E-MTAB-10042	yes	7.34
E-ANND-3	no	1.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CTCF, EGR1

miRNA regulators (miRDB)

31 targeting EPX, 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-6127	100.00	66.76	2188
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-6858-3P	96.37	64.41	771
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-103B	95.51	66.85	441

Literature-anchored findings (GeneRIF, showing 27)

• induces surface alteration, killing, and lysis of Mycobacterium tuberculosis (PMID:12540536)
• results suggest that Pro358Leu in EPO is strongly involved in the development of cedar pollinosis (PMID:14657871)
• Polymorphisms of the eosinophil peroxidase gene may be associated with Japanese cedar pollinosis. (PMID:15316147)
• Analysis of the role of thiocyanate (SCN-), in modulating the catalytic activity of myeloperoxidase (MPO) and other members of the lactoperoxidase (LPO) and eosinophil peroxidase (EPO) (PMID:15894800)
• The mechanisms by which eosinophil peroxidase oxidizes nitrite are reported. (PMID:16336215)
• post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase (PMID:18694936)
• No variation in genes eosinophil peroxidase for Atopic dermatitis pathogenesis in this German cohort. (PMID:19014520)
• Genetic variability in the EPO gene may contribute to the susceptibility to allergic rhinitis (or related phenotypes) in the Czech population. (PMID:19439985)
• EPO-dependent oxidative damage may play a role in tissue injury in bisulfite-exacerbated eosinophilic inflammatory disorders (PMID:20501663)
• HER2 was identified as a novel mediator of eosinophil peroxidase signaling. Eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation. (PMID:21454806)
• A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. (PMID:22702502)
• Data indicate that eosinophil peroxidase (EPX)-based ELISA is the only eosinophil-specific assay. (PMID:22750539)
• Polymorphisms of EPX and ECP are associated to inflammatory bowel disease in an age and gender dependent manne. (PMID:23197886)
• Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia. (PMID:23931643)
• report the prevalence of a common SNP in the eosinophil protein x/eosinophil-derived neurotoxin (EPX/EDN, RNase2) and the association with the cellular contents of EPX/EDN and ECP (PMID:24738159)
• mRNA levels of eosinophil granule proteins, rather than sputum eosinophil%, may reflect airway hyperresponsiveness and airflow limitation. (PMID:24814827)
• A preferential role of EPO signaling via a specific surface receptor that leads to neural plasticity. (PMID:24937179)
• Myeloperoxidase and eosinophil peroxidase are readily internalized by HUVEC cells where they promote cellular proliferation, migration, invasion, and stimulate angiogenesis both in vitro and in vivo. (PMID:26386352)
• there is a strong association in a given patient between both nasal and pharyngeal EPX levels and the eosinophil percentage of induced sputum. (PMID:26645423)
• The main significance of this work is the discovery of EPO as a novel ligand for the HER2 receptor. Following HER2 activation, EPO induces activation of FAK and subsequent activation of beta1-integrin, via inside-out signaling. This complex results in downstream activation of ERK1/2 and a sustained up regulation of both MUC4 and the HER2 receptor (PMID:27519953)
• EPO-mediated protein carbamylation is promoted during allergen-induced asthma exacerbation, and can both modulate immune responses and trigger a cascade of many of the inflammatory signals present in asthma. (PMID:27587397)
• peroxidase enzymes, like MPO and EPO, may play a fundamental role in inhibiting RANKL-induced osteoclast differentiation at inflammatory sites of bone fracture and injury. (PMID:27836774)
• Both MPO and EPO are causatively involved in breast cancer progression and identified as potential therapeutic targets whereby specific novel inhibitors may reduce tumor growth and limit the occurrence of metastasis. (PMID:28260049)
• EPX is a useful biomarker for eosinophilic inflammation in chronic rhinosinusitis. (PMID:30738839)
• Eosinophil Peroxidase: A Biomarker for Eosinophilic Chronic Rhinosinusitis Agnostic of Polyp Status. (PMID:37255054)
• Eosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase. (PMID:38316791)
• Eosinophil peroxidase promotes bronchial epithelial cells to secrete asthma-related factors and induces the early stage of airway remodeling. (PMID:38663494)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpx	ENSDARG00000019521
mus_musculus	Epx	ENSMUSG00000052234
rattus_norvegicus	Epx	ENSRNOG00000008707
drosophila_melanogaster	Pxd	FBGN0004577
drosophila_melanogaster	Pxn	FBGN0011828
drosophila_melanogaster	CG4009	FBGN0038469
drosophila_melanogaster	cysu	FBGN0038511
caenorhabditis_elegans		WBGENE00004256
caenorhabditis_elegans		WBGENE00004257
caenorhabditis_elegans		WBGENE00016700
caenorhabditis_elegans		WBGENE00019613

Paralogs (5): MPO (ENSG00000005381), TPO (ENSG00000115705), PXDN (ENSG00000130508), PXDNL (ENSG00000147485), LPO (ENSG00000167419)

Protein

Protein identifiers

Eosinophil peroxidase — P11678 (reviewed: P11678)

All UniProt accessions (1): P11678

UniProt curated annotations — full annotation on UniProt →

Function. Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils. Shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv by inducing bacterial fragmentation and lysis.

Subunit / interactions. Tetramer of two light chains and two heavy chains.

Subcellular location. Cytoplasmic granule.

Disease relevance. Eosinophil peroxidase deficiency (EPXD) [MIM:261500] A rare abnormality without clinical symptoms characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix in eosinophils. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Ca(2+) ion per heterodimer. Binds 1 heme b (iron(II)-protoporphyrin IX) covalently through ester linkages to hydroxylated methyl groups formed auto-catalytically with hydrogen peroxide at the heme C-1 and C-5 positions. The ester linkage to Asp-232 was observed in 30% of the chains.

Similarity. Belongs to the peroxidase family. XPO subfamily.

RefSeq proteins (1): NP_000493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010255	Haem_peroxidase_sf	Homologous_superfamily
IPR019791	Haem_peroxidase_animal	Family
IPR037120	Haem_peroxidase_sf_animal	Homologous_superfamily

Pfam: PF03098

Catalyzed reactions (Rhea), 1 shown:

• 2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2 H2O (RHEA:56136)

UniProt features (48 total): sequence variant 16, binding site 8, glycosylation site 6, disulfide bond 6, sequence conflict 5, chain 2, signal peptide 1, propeptide 1, site 1, modified residue 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8OGI	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11678-F1	92.40	0.82

Functional residue map

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

Catalytic / active sites (2): 377 (transition state stabilizer); 233 (proton acceptor)

Ligand- & substrate-binding residues (8): 312; 380 (covalent); 474 (axial binding residue); 232 (covalent; partial); 234; 306; 308; 310

Post-translational modifications (1): 488

Disulfide bonds (6): 141–152, 253–263, 257–281, 359–370, 578–635, 676–701

Glycosylation sites (6): 52, 113, 327, 363, 700, 708

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 371 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMOGLOBIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE

GO Biological Process (10): defense response to nematode (GO:0002215), response to oxidative stress (GO:0006979), negative regulation of macrophage cytokine production (GO:0010936), negative regulation of interleukin-10 production (GO:0032693), negative regulation of interleukin-5 production (GO:0032714), positive regulation of interleukin-4 production (GO:0032753), defense response to bacterium (GO:0042742), hydrogen peroxide catabolic process (GO:0042744), eosinophil migration (GO:0072677), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (5): peroxidase activity (GO:0004601), heme binding (GO:0020037), metal ion binding (GO:0046872), lactoperoxidase activity (GO:0140825), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
negative regulation of cytokine production	2
response to other organism	1
response to stress	1
negative regulation of cytokine production involved in immune response	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-5 production	1
regulation of interleukin-5 production	1
positive regulation of cytokine production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
response to bacterium	1
catabolic process	1
hydrogen peroxide metabolic process	1
granulocyte migration	1
cellular detoxification	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
tetrapyrrole binding	1
cation binding	1
peroxidase activity	1
catalytic activity	1
cellular anatomical structure	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPX	RNASE2	P10153	999
EPX	RNASE3	P12724	999
EPX	IL5	P05113	719
EPX	GADD45GIP1	Q8TAE8	717
EPX	PRG2	P13727	715
EPX	IL4	P05112	690
EPX	MRGPRX2	Q96LB1	642
EPX	CCL11	P50877	641
EPX	IL5RA	Q01344	621
EPX	CCR3	P51677	600
EPX	IL13	P35225	586
EPX	SIGLEC8	Q9NYZ4	579
EPX	CCL26	Q9Y258	579
EPX	CLC	Q05315	571
EPX	CCL24	O00175	571

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TMEM237	CLGN	psi-mi:“MI:0914”(association)	0.530
NCK1	EPX	psi-mi:“MI:0915”(physical association)	0.400
EPX	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
EPX	PLCG1	psi-mi:“MI:0915”(physical association)	0.400
EPX	TTC19	psi-mi:“MI:0915”(physical association)	0.400
TMEM237	JCHAIN	psi-mi:“MI:0914”(association)	0.350
TMEM74	KLRG2	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
RAB11A	SERPINA3	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): EPX (Affinity Capture-MS), EPX (Affinity Capture-MS), EPX (Affinity Capture-MS), EPX (Affinity Capture-MS), TTC19 (Affinity Capture-MS), EPX (Affinity Capture-MS), EPX (Affinity Capture-MS), EPX (Affinity Capture-MS), EPX (Affinity Capture-MS), HNRNPA2B1 (Cross-Linking-MS (XL-MS)), DNAH2 (Cross-Linking-MS (XL-MS)), DNAH6 (Cross-Linking-MS (XL-MS)), HNRNPA1L2 (Cross-Linking-MS (XL-MS)), HNRNPA3 (Cross-Linking-MS (XL-MS)), EPX (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1Y9G8H0, A0A452E9Y6, A1A4K5, A1KZ92, A5JUY8, P05164, P07202, P09933, P11247, P11678, P14650, P15396, P22079, P22413, P35419, P43446, P49290, P49340, P57110, P70669, P78562, P80025, Q01603, Q08410, Q13822, Q20616, Q23490, Q2KIY5, Q3TCN2, Q4QQW8, Q5R5M5, Q5SW46, Q64610, Q6DYE8, Q6P9A2, Q801F7, Q8CIY2, Q8HYB7, Q8HZK2, Q8HZK3

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A4IGL7, A5JUY8, B3A0P3, B3A0Q8, G5EG78, H2A0M7, O61213, P09933, P11247, P11678, P22079, P80025, P82600, P90820, Q01603, Q20616, Q23490, Q3UQ28, Q5SW46, Q6TMK4, Q7QH73, Q8CIY2, Q8HYB7, Q8R481, Q92626, Q9ES45, Q9VEG6, Q9VZZ4, A8WQH2, O02768, P05164, P07202, P14650, P35355, P35419, P49290, Q1ENI8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
EPX	“up-regulates activity”	PRG2	“post translational modification”
EPX	“up-regulates activity”	RNASE2	“post translational modification”
EPX	“up-regulates activity”	RNASE3	“post translational modification”
EPX	“up-regulates activity”	EPX	“post translational modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	9
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1610 predictions. Top by Δscore:

Variant	Effect	Δscore
17:58193129:G:GT	donor_gain	1.0000
17:58193506:G:GT	donor_gain	1.0000
17:58193612:G:GT	donor_gain	1.0000
17:58193711:C:G	acceptor_gain	1.0000
17:58193711:CAGAT:C	acceptor_loss	1.0000
17:58193712:A:AG	acceptor_gain	1.0000
17:58193712:AGAT:A	acceptor_gain	1.0000
17:58193713:G:GG	acceptor_gain	1.0000
17:58193713:GA:G	acceptor_gain	1.0000
17:58193713:GAT:G	acceptor_gain	1.0000
17:58193713:GATG:G	acceptor_gain	1.0000
17:58193713:GATGT:G	acceptor_gain	1.0000
17:58193828:ACAA:A	donor_gain	1.0000
17:58193832:G:T	donor_loss	1.0000
17:58193832:GTGC:G	donor_gain	1.0000
17:58193833:T:G	donor_loss	1.0000
17:58194065:G:GT	donor_gain	1.0000
17:58194093:G:GG	donor_gain	1.0000
17:58194962:A:G	acceptor_loss	1.0000
17:58194963:GGTCC:G	acceptor_gain	1.0000
17:58195167:CAAGG:C	donor_loss	1.0000
17:58195168:AAG:A	donor_loss	1.0000
17:58195171:G:GC	donor_loss	1.0000
17:58195172:T:A	donor_loss	1.0000
17:58196934:CTCA:C	acceptor_loss	1.0000
17:58196935:TCA:T	acceptor_loss	1.0000
17:58196936:CA:C	acceptor_loss	1.0000
17:58196937:A:AC	acceptor_loss	1.0000
17:58196937:A:AG	acceptor_gain	1.0000
17:58196938:G:GG	acceptor_gain	1.0000

AlphaMissense

4628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:58194977:C:T	S203F	0.995
17:58199109:G:C	R397P	0.995
17:58195067:A:C	H233P	0.994
17:58199097:G:C	R393P	0.994
17:58200364:C:A	N559K	0.994
17:58200364:C:G	N559K	0.994
17:58200378:G:C	R564P	0.994
17:58203092:T:A	W574R	0.993
17:58203092:T:C	W574R	0.993
17:58195048:T:A	W227R	0.992
17:58195048:T:C	W227R	0.992
17:58195066:C:G	H233D	0.992
17:58200374:A:C	S563R	0.992
17:58200376:C:A	S563R	0.992
17:58200376:C:G	S563R	0.992
17:58199175:G:C	R419P	0.991
17:58199653:T:C	F466L	0.991
17:58199655:C:A	F466L	0.991
17:58199655:C:G	F466L	0.991
17:58200372:G:C	R562P	0.991
17:58203096:G:C	R575T	0.990
17:58203215:T:A	W615R	0.990
17:58203215:T:C	W615R	0.990
17:58195073:T:C	L235P	0.989
17:58200348:A:T	D554V	0.989
17:58203105:G:A	C578Y	0.989
17:58204301:T:A	C676S	0.989
17:58204302:G:C	C676S	0.989
17:58194977:C:A	S203Y	0.988
17:58195069:G:C	D234H	0.988

dbSNP variants (sampled 300 via entrez): RS1000228687 (17:58196837 G>A,T), RS1000836731 (17:58192330 C>A), RS1000850455 (17:58197809 A>G), RS1000932455 (17:58192514 G>T), RS1001276555 (17:58193992 A>G), RS1001502124 (17:58195739 C>T), RS1001503320 (17:58195618 T>G), RS1001680235 (17:58201465 C>T), RS1002064254 (17:58198717 T>C), RS1002343533 (17:58191591 T>C), RS1002525434 (17:58204528 A>C), RS1002560996 (17:58198432 G>A), RS1002722081 (17:58201363 C>A,T), RS1002948590 (17:58195306 C>A,T), RS1003137914 (17:58194191 C>G,T)

Disease associations

OMIM: gene MIM:131399 | disease phenotypes: MIM:261500

GenCC curated gene-disease

Disease	Classification	Inheritance
eosinophil peroxidase deficiency	Limited	Autosomal recessive

Mondo (1): eosinophil peroxidase deficiency (MONDO:0043364)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0034253	Eosinophil nuclear hypersegmentation

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564893	Presentey Anomaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2438 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
7-{18-oxa-3,4,10-triazatetracyclo[17.3.1.13,6.113,1 7 ]pentacosa-1(23),4,6(25),13,15,17(24),19,21-octaen-7-yl}-3H-[1,2,3]triazolo[4,5-b]pyridin-5-amine	IC50	37 nM	US-10577383: Macrocyclic inhibitors of myeloperoxidase
7-{14′-Oxa-3′,4′,10′-triazaspiro[cyclopropane-1,12′-tricyclo[13.3.1.13,6]icosane]-1′(19′),4′,6′(20′),15′,17′-pentaen-7′-yl}-3H-[1,2,3]triazolo[4,5-b]pyridin-5-amine	IC50	63 nM	US-10577383: Macrocyclic inhibitors of myeloperoxidase
7-{18-oxa-3,4,10-triazatetracyclo[17.3.1.13,6.112,1 6 ]pentacosa-1(23),4,6(25),12,14,16(24),19,21-octaen-7-yl}-3H-[1,2,3]triazolo[4,5-b]pyridin-5-amine	IC50	190 nM	US-10577383: Macrocyclic inhibitors of myeloperoxidase
7-{3-Oxa-10,11,17-triazatetracyclo[16.2.2.14,8.110,13]tetracosa-4,6,8(24),11,13	IC50	220 nM	US-10577383: Macrocyclic inhibitors of myeloperoxidase

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.82	IC50	15	nM	CHEMBL333928
7.77	IC50	17	nM	CHEMBL333928
7.66	IC50	22	nM	CHEMBL4482878
7.50	IC50	32	nM	CHEMBL4753981
7.04	IC50	92	nM	CHEMBL4747269
6.80	IC50	160	nM	CHEMBL4282403
6.44	IC50	360	nM	CHEMBL4790231

PubChem BioAssay actives

7 with measured affinity, of 8 total; 6 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
7-phenylmethoxy-2H-triazolo[4,5-d]pyrimidin-5-amine	1416586: Inhibition of eosinophil peroxidase (unknown origin)assessed as reduction in H2O2-catalyzed 3-bromo tyrosine formation using tyrosine and potassium bromide preincubated for 10 mins followed by tyrosine/potassium bromide/H2O2 addition and measured after 15 mins by RP-UPLC analysis	ic50	0.0150	uM
7-[(2-fluorophenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine	1533024: Inhibition of human EPX bromination activity assessed as reduction in H2O2 catalyzed 3-bromo tyrosine formation from tyrosine and potassium bromide preincubated for 10 mins followed by tyrosine/potassium bromide/H2O2 addition measured after 15 mins by RP-UPLC analysis	ic50	0.0220	uM
7-benzyl-2H-triazolo[4,5-b]pyridin-5-amine	1698298: Inhibition of human EPX bromination activity using tyrosine as substrate by measuring 3-bromo tyrosine formation incubated for 10 mins	ic50	0.0320	uM
7-[(1R)-1-phenyl-3-[[(1S,3S)-3-phenyl-2,3-dihydro-1H-inden-1-yl]amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine	1698298: Inhibition of human EPX bromination activity using tyrosine as substrate by measuring 3-bromo tyrosine formation incubated for 10 mins	ic50	0.0920	uM
5-(2,4,5-trichlorophenoxy)pyridin-2-amine	1416586: Inhibition of eosinophil peroxidase (unknown origin)assessed as reduction in H2O2-catalyzed 3-bromo tyrosine formation using tyrosine and potassium bromide preincubated for 10 mins followed by tyrosine/potassium bromide/H2O2 addition and measured after 15 mins by RP-UPLC analysis	ic50	0.1600	uM
7-[(1R)-1-phenyl-3-[(4-phenyl-1-bicyclo[2.2.2]octanyl)amino]propyl]-2H-triazolo[4,5-b]pyridin-5-amine	1698298: Inhibition of human EPX bromination activity using tyrosine as substrate by measuring 3-bromo tyrosine formation incubated for 10 mins	ic50	0.3600	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
lasiocarpine	decreases expression	1
chlortoluron	decreases expression	1
terbufos	increases methylation	1
cerous chloride	decreases expression	1
lanthanum chloride	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	decreases expression	1
tamibarotene	decreases expression	1
azoxystrobin	decreases expression	1
cyproconazole	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
isonicotinyl-NAD	increases chemical synthesis, increases oxidation	1
Acetaminophen	increases expression	1
Arbutin	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Fonofos	increases methylation	1
Isoniazid	increases oxidation, increases chemical synthesis	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Butyric Acid	increases expression	1
Permethrin	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4263010	Binding	Inhibition of eosinophil peroxidase (unknown origin)assessed as reduction in H2O2-catalyzed 3-bromo tyrosine formation using tyrosine and potassium bromide preincubated for 10 mins followed by tyrosine/potassium bromide/H2O2 addition and me	Triazolopyrimidines identified as reversible myeloperoxidase inhibitors. — Medchemcomm
CHEMBL677515	Functional	Compound was evaluated for the inhibition of serum-opsonized zymosan stimulated eosinophil peroxidase release from human eosinophil; Inactive	Novel benzothiophene-, benzofuran-, and naphthalenecarboxamidotetrazoles as potential antiallergy agents. — J Med Chem

Clinical trials (associated diseases)

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