Eosinophil peroxidase deficiency

Summary

Eosinophil peroxidase deficiency (MONDO:0043364) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	eosinophil peroxidase deficiency
Mondo ID	MONDO:0043364
MeSH	C564893
OMIM	261500
SNOMED CT	711160007
UMLS	C1850000
MedGen	342386
GARD	0012361
Is cancer (heuristic)	no

Also known as: eosinophil peroxidase deficiency · eosinophil peroxidase deficiency, partial · EPXD · peroxidase and phospholipid deficiency in eosinophils · Presentey anomaly

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › eosinophil peroxidase deficiency

Related subtypes (22): human monocytic ehrlichiosis, B cell deficiency, leukopenia, B-cell neoplasm, dendritic cell sarcoma, human granulocytic anaplasmosis, T-cell leukemia, phagocyte bactericidal dysfunction, EBV-positive T-cell lymphoproliferative disorder of childhood, small intestinal enteropathy-associated T-cell lymphoma, pituitary gland basophil adenoma, leukostasis, mastocytosis, hereditary neutrophilia, Pelger-Huet anomaly, functional neutrophil defect, thymoma type B, POEMS syndrome, Langerhans cell histiocytosis, subcutaneous panniculitis-like T-cell lymphoma, eosinophil disorder, mast cell activation syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 affects, 1 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16615	NM_000502.6(EPX):c.857G>A (p.Arg286His)	EPX	Affects	no assertion criteria provided
16616	NC_000017.11:g.58200228dup	EPX	Affects	no assertion criteria provided
208340	NM_000502.6(EPX):c.1942G>A (p.Asp648Asn)	EPX	Affects	no assertion criteria provided
3779621	NM_000502.6(EPX):c.158G>A (p.Trp53Ter)	EPX	Uncertain significance	criteria provided, single submitter
779025	NM_000502.6(EPX):c.801+1G>A	EPX	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
EPX	Limited	Autosomal recessive	eosinophil peroxidase deficiency	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EPX	HGNC:3423	ENSG00000121053	P11678	Eosinophil peroxidase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPX	Eosinophil peroxidase	Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPX	Other/Unknown	no		Haem_peroxidase_sf, Haem_peroxidase_animal, Haem_peroxidase_sf_animal

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow	1
male germ line stem cell (sensu Vertebrata) in testis	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPX	113	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, trabecular bone tissue, bone marrow

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPX	763

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPX	P11678	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neutrophil degranulation	1	23.1×	0.043	EPX

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
eosinophil migration	1	8426.0×	0.001	EPX
defense response to nematode	1	3370.4×	0.001	EPX
negative regulation of interleukin-5 production	1	1872.4×	0.002	EPX
negative regulation of macrophage cytokine production	1	1203.7×	0.002	EPX
negative regulation of interleukin-10 production	1	732.7×	0.002	EPX
hydrogen peroxide catabolic process	1	674.1×	0.002	EPX
positive regulation of interleukin-4 production	1	561.7×	0.002	EPX
response to oxidative stress	1	130.6×	0.009	EPX
defense response to bacterium	1	108.0×	0.009	EPX

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPX	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EPX	4	Binding:3, Functional:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	EPX

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EPX	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.