MPO
protein-codingmyeloperoxidase
Gene summary
Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Produced as a single chain precursor, myeloperoxidase is subsequently cleaved into a light and heavy chain. The mature myeloperoxidase is a tetramer composed of 2 light chains and 2 heavy chains. This enzyme produces hypohalous acids central to the microbicidal activity of neutrophils. [provided by RefSeq, Nov 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009694
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Many individuals (including with complete myeloperoxidase deficiency) do not show obvious clinical sequelae, but increased candiasis and incidence of severe infections has been reported in some individuals, and awareness may allow prompt recognition and treatment, which may reduce morbidity and mortality
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MPO variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000250.2. 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 | 2 | 25 | 2 | 29 | ||
| missense | 2 | 3 | 107 | 12 | 1 | 125 |
| nonsense | 1 | 6 | 7 | |||
| start loss | 0 | |||||
| frameshift | 1 | 5 | 1 | 7 | ||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 4 | 17 | 110 | 37 | 3 | 171 |
Highest pathogenic variant AF is 0.0055447603
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000241.1 | 12 | MANE Select | |
| Ensembl | ENSP00000225275.3 | 12 | MANE Select | |
| Ensembl | ENSP00000464668.1 | 3 | Standard | |
| Ensembl | ENSP00000514272.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Acute myeloid leukemia - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Drug metabolism - other enzymes - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Carbamazepine Pathway, Pharmacokinetics
Biological Process
- response to yeast
- hypochlorous acid biosynthetic process
- respiratory burst involved in defense response
- defense response
- response to oxidative stress
Molecular Function
- chromatin binding
- peroxidase activity
- heparin binding
- heme binding
- metal ion binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- cytoplasm
- lysosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225275
- Coding exons
- 12
- Length
- 11080
- Individuals with no LoFs
- 124319
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 1426
- Defined
- 125748
- p
- 0.00570
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.323 | 449 | 469 | 0.958 | 0.0000331 | 4800 |
| Missense (PolyPhen) | 163 | 186.89 | 0.87216 | 1932 | ||
| Synonymous | -0.0335 | 200 | 199 | 1.00 | 0.0000141 | 1545 |
| Loss of Function | 0.921 | 25 | 30.5 | 0.820 | 0.00000162 | 318 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0017 | notable |
| Latino/Admixed American | 0.0034 | 0.0034 | notable |
| Ashkenazi Jewish | 0.013 | 0.013 | notable |
| East Asian | 0.0018 | 0.0018 | notable |
| Finnish | 0.0028 | 0.0022 | notable |
| European (Non-Finnish) | 0.0092 | 0.0091 | notable |
| South Asian | 0.00063 | 0.00059 | rare |
| Other | 0.0033 | 0.0031 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. {ECO:0000269|PubMed:9922160}.;
- Disease
- DISEASE: Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.902
Intolerance Scores
- LoFtool
- 0.862
- RVIS EVS
- -0.15
- RVIS percentile EVS
- 42.3
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.875
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |