EPX

protein-coding

eosinophil peroxidase

Gene summary

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. [provided by RefSeq, Feb 2016]

MANE transcript

NM_000502.6

Inheritance

ClinVar variants

U:143B:20

Top phenotype

Eosinophil peroxidase deficiency

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr17:58,192,726-58,205,174

External References & Databases

Ensembl (ENSG00000121053)

Transcript & Mutation Effects

hg38 • Region Span ~12.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

eosinophil peroxidase deficiencyNO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0043364

Submitter: Ambry Genetics

eosinophil peroxidase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0043364

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Eosinophil peroxidase deficiencyAR

Manifestation: General

Intervention: General

Rationale: The clinical relevance is unclear

Refs: 7809065

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPX variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 145

not providedTotal: 14

Eosinophil peroxidase deficiencyTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000502.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	1 clinvar	7
missense			140 clinvar	7 clinvar	4 clinvar	151
nonsense			1 clinvar		1 clinvar	2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar	1 clinvar		3
Total	0	0	143	14	6	163

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000502.6	RefSeq	NP_000493.1	12	MANE Select
ENST00000225371.6	Ensembl	ENSP00000225371.5	12	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Asthma - Homo sapiens (human)
Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

defense response to nematode
response to oxidative stress
negative regulation of interleukin-10 production
negative regulation of interleukin-5 production
positive regulation of interleukin-4 production

Molecular Function

peroxidase activity
heme binding
metal ion binding

Cellular Component

extracellular region
extracellular space
cytoplasm
secretory granule lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000225371
Coding exons: 12
Length: 12438
Individuals with no LoFs: 122463
Homozygous LoFs: 33
Heterozygous LoFs: 3252
Defined: 125748
p: 0.0131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.957	503	446	1.13	0.0000321	4598
Missense (PolyPhen)		161	149.28	1.0785		1787
Synonymous	-0.00419	180	180	1.00	0.0000114	1541
Loss of Function	0.479	32	35.1	0.913	0.00000249	328

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0063	0.0064	notable
Latino/Admixed American	0.0071	0.0071	notable
Ashkenazi Jewish	0.012	0.012	notable
East Asian	0.00038	0.00038	rare
Finnish	0.0075	0.0075	notable
European (Non-Finnish)	0.015	0.015	notable
South Asian	0.029	0.029	notable
Other	0.015	0.016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:12540536, ECO:0000269|PubMed:18694936}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:7809065}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.279

Intolerance Scores

LoFtool: 0.861
RVIS EVS: 1.14
RVIS percentile EVS: 92.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.843

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium