Alt. symbols:

Approved name: myeloperoxidase
Alt. names: myeloperoxidase

Location: 17q22: 58269855 - 58280935 (-)
Gene type: protein_coding, 7 transcripts.

Scores: LoFtool: 0.862000 | pLI: 0.00000000 | LOEUF: 1.145

HGNC: 7218

NCBI: 4353, RefSeq: NG_009629.1

Ensembl: ENSG00000005381.9

LRG_84 | Status: public

OMIM: 606989

Expression | ProteinAtlas

MPO encodes myeloperoxidase, a lysosomal hemoprotein located in the azurophilic granules of polymorphonuclear (PMN) leukocytes and monocytes. In response to stimulation, MPO is activated into a transient intermediate with potent microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids and other toxic intermediates, all of which contribute to enhanced PMN microbicidal activity.

Biallelic mutations in MPO cause Myeloperoxidase deficiency, an autosomal recessive disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes. This is considered one of the most common inherited phagocyte defects with estimated prevalence of one in several thousand (PMID: 6267975). Thus far, homozygous or compound heterozygous missense, nonsense, frameshift, and splice site mutations have been described, though biochemical and clinical phenotypes do not appear to consistently conform to a simple autosomal recessive inheritance pattern. In the absence of MPO, auxiliary mechanisms protect most MPO-deficient hosts from clinically significant sequelae, except for some persons with diabetes mellitus who may suffer severe candidal disease. Measurement of bulk peroxidase activity in leukocytes may not accurately detect MPO deficiency, which can be masked by the normal activity of eosinophil peroxidase. It has also been noted that MPO deficiency may lead to artefactual pseudoneutropenia with the use of automated blood cell counters. Those that identify different types of leukocytes based on mean peroxidase index (MPXI) in addition to size and staining properties may incorrectly count MPO-deficient neutrophils as monocytes with lower MPXI values, potentially leading to an erroneous diagnosis of severe neutropenia. Thus, manual differential counting is recommended for confirmation in the setting of low neutrophil count with elevated monocyte count. MPO variants have been implicated in properties such as protection against lung cancer in smokers} and susceptibility to Alzheimer disease [MIM:104300]. In the latter case, Zappia et al. (2004) noted that MPO polymorphism genotype -463G/G was associated with an odds ratio of 1.65 for development of Alzheimer disease independent of APOE4 status (PMID: 15023809). More recently, predominantly biallelic MPO variants have been linked to the development of generalized pustular psoriasis (GPP) by 2 groups (PMID: 32758447, 32758448). Indeed Haskamp et al. (2020) proposed that GPP has an oligogenic inheritance pattern, with MPO variants contributing to the variability in penetrance and age of onset. Of note, the dihydrorhodamine (DHR) signal seen on routine diagnostic screening for chronic granulomatous disease (CGD) requires both an intact NADPH-oxidase activity as well as the presence of a peroxidase such as MPO. Thus, complete MPO deficiency may be misdiagnosed as CGD due to a false positive DHR that appears to be significantly below normal on flow cytometry (PMID: 17384005, 27301573). However, as there is considerable variability in the DHR fluorescence of complete MPO-deficient patients, the DHR assay may not be reliable for detecting MPO deficiency. Mauch et al. (2007) additionally proposed that MPO-deficient patients could be distinguished from CGD patients on the basis of 3 findings: 1) Functionally normal eosinophils, 2) restoration of DHR signal upon addition of recombinant human MPO, and 2) a strong lucigenin-enhanced chemiluminescence (LCL) signal in neutrophils (vs a reduced signal in CGD patients) (PMID: 17384005). [Load More]