LPO

Summary

LPO (lactoperoxidase, HGNC:6678) is a protein-coding gene on chromosome 17q22, encoding Lactoperoxidase (P22079). Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2).

This gene encodes a member of the peroxidase family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Following its secretion from salivary, mammary, and other mucosal glands, this enzyme catalyzes the generation of the antimicrobial substance hypothiocyanous acid. This gene is present in a gene cluster on chromosome 17. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed.

Source: NCBI Gene 4025 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 126 total — 1 pathogenic
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 4 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.23 (unconstrained)
• MANE Select transcript: NM_006151
• Notable: 126 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6678
Approved symbol	LPO
Name	lactoperoxidase
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	SPO
Ensembl gene	ENSG00000167419
Ensembl biotype	protein_coding
OMIM	150205
Entrez	4025

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000262290

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 3, TSL 3: 2, TSL 5: 1

ENST00000262290, ENST00000389576, ENST00000421678, ENST00000543544, ENST00000578403, ENST00000578643, ENST00000580346, ENST00000580890, ENST00000581008, ENST00000582328, ENST00000582684, ENST00000866990, ENST00001142473

RefSeq mRNA: 2 — MANE Select: NM_006151 NM_001160102, NM_006151

CCDS: CCDS32689, CCDS54149

Canonical transcript exons

ENST00000262290 — 13 exons

Exon	Start	End
ENSE00002204284	58252182	58252506
ENSE00002227590	58250415	58250621
ENSE00003525065	58249566	58249695
ENSE00003555595	58267349	58267586
ENSE00003584486	58254811	58254971
ENSE00003589986	58249060	58249177
ENSE00003597948	58243994	58244081
ENSE00003607267	58266153	58266326
ENSE00003636259	58242978	58243055
ENSE00003666965	58247478	58247638
ENSE00003678442	58264722	58264974
ENSE00003889096	58238584	58238739
ENSE00004800969	58267787	58268518

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 99.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.7884 / max 3878.4082, expressed in 50 samples.

Highest expression (Bgee): parotid gland, olfactory segment of nasal mucosa, trachea, saliva-secreting gland, minor salivary gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPO is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.2e-02	-0.16	17:58243910:G:A
Testis	eqtl	2.3e-02	-0.13	17:58250638:A:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
161902	2.5260	15
161900	2.5084	38
161898	0.5710	18
161901	0.1562	7
161899	0.0267	5

Top tissues by expression

showing 100 of 247 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.61	gold quality
trachea	UBERON:0003126	97.49	gold quality
saliva-secreting gland	UBERON:0001044	87.16	gold quality
minor salivary gland	UBERON:0001830	83.82	gold quality
mouth mucosa	UBERON:0003729	79.68	gold quality
nasal cavity mucosa	UBERON:0001826	79.39	gold quality
Brodmann (1909) area 10	UBERON:0013541	70.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.00	gold quality
bone marrow cell	CL:0002092	65.19	silver quality
endometrium epithelium	UBERON:0004811	64.72	gold quality
frontal pole	UBERON:0002795	64.43	gold quality
middle frontal gyrus	UBERON:0002702	64.24	gold quality
paraflocculus	UBERON:0005351	64.10	gold quality
bone marrow	UBERON:0002371	63.08	gold quality
diaphragm	UBERON:0001103	61.61	gold quality
gingiva	UBERON:0001828	61.36	silver quality
pharyngeal mucosa	UBERON:0000355	61.35	silver quality
substantia nigra	UBERON:0002038	60.09	gold quality
substantia nigra pars reticulata	UBERON:0001966	60.07	gold quality
superior surface of tongue	UBERON:0007371	60.02	gold quality
sperm	CL:0000019	59.96	gold quality
pancreatic ductal cell	CL:0002079	59.89	silver quality
male germ cell	CL:0000015	59.36	gold quality
midbrain	UBERON:0001891	58.17	gold quality
tongue	UBERON:0001723	57.60	silver quality
tonsil	UBERON:0002372	57.17	gold quality
stromal cell of endometrium	CL:0002255	57.08	gold quality
vena cava	UBERON:0004087	56.31	gold quality
gingival epithelium	UBERON:0001949	56.24	gold quality
prefrontal cortex	UBERON:0000451	55.85	gold quality
mucosa of sigmoid colon	UBERON:0004993	55.82	gold quality
jejunal mucosa	UBERON:0000399	55.80	gold quality
cerebellar vermis	UBERON:0004720	55.77	gold quality
colonic mucosa	UBERON:0000317	55.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	55.60	gold quality
monocyte	CL:0000576	55.04	gold quality
mononuclear cell	CL:0000842	54.99	gold quality
right testis	UBERON:0004534	54.80	gold quality
leukocyte	CL:0000738	54.64	gold quality
kidney epithelium	UBERON:0004819	54.62	gold quality
quadriceps femoris	UBERON:0001377	54.44	gold quality
vastus lateralis	UBERON:0001379	53.89	gold quality
thymus	UBERON:0002370	53.84	gold quality
nasal cavity epithelium	UBERON:0005384	53.71	gold quality
trabecular bone tissue	UBERON:0002483	53.62	gold quality
metanephric glomerulus	UBERON:0004736	53.56	gold quality
left testis	UBERON:0004533	53.43	gold quality
testis	UBERON:0000473	53.31	gold quality
biceps brachii	UBERON:0001507	53.20	gold quality
islet of Langerhans	UBERON:0000006	53.14	gold quality
decidua	UBERON:0002450	52.10	gold quality
frontal cortex	UBERON:0001870	52.00	gold quality
skeletal muscle tissue	UBERON:0001134	51.31	gold quality
epithelial cell of pancreas	CL:0000083	51.18	gold quality
neocortex	UBERON:0001950	51.16	gold quality
blood	UBERON:0000178	50.93	gold quality
body of tongue	UBERON:0011876	50.64	gold quality
muscle tissue	UBERON:0002385	50.45	gold quality
myocardium	UBERON:0002349	50.39	gold quality
hair follicle	UBERON:0002073	50.12	gold quality
cortical plate	UBERON:0005343	50.11	gold quality
oral cavity	UBERON:0000167	50.02	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.93	gold quality
cingulate cortex	UBERON:0003027	49.60	gold quality
layer of synovial tissue	UBERON:0007616	49.50	gold quality
sural nerve	UBERON:0015488	49.50	gold quality
anterior cingulate cortex	UBERON:0009835	49.35	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
jejunum	UBERON:0002115	48.69	gold quality
oviduct epithelium	UBERON:0004804	48.67	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
cerebral cortex	UBERON:0000956	48.40	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
deltoid	UBERON:0001476	47.94	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
squamous epithelium	UBERON:0006914	47.62	gold quality
primary visual cortex	UBERON:0002436	47.40	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
placenta	UBERON:0001987	47.18	gold quality
cerebellum	UBERON:0002037	47.07	silver quality
gluteal muscle	UBERON:0002000	47.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
granulocyte	CL:0000094	46.97	silver quality
Brodmann (1909) area 9	UBERON:0013540	46.96	gold quality
right frontal lobe	UBERON:0002810	46.84	gold quality
cerebellar cortex	UBERON:0002129	46.67	silver quality
lateral globus pallidus	UBERON:0002476	46.43	gold quality
cerebellar hemisphere	UBERON:0002245	46.42	silver quality
hypothalamus	UBERON:0001898	46.29	gold quality
brain	UBERON:0000955	46.25	gold quality
occipital lobe	UBERON:0002021	46.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	13.00
E-ANND-3	yes	6.20

HPA expression

RNA tissue specificity: Tissue enriched

39 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Salivary gland	tissue	967.3	high
Caudate putamen	tissue	1.9
Frontal cortex	tissue	1.2
Pancreas	tissue	1.1	not detected
Testis	tissue	0.8	not detected
Postcentral gyrus	tissue	0.8
Nucleus accumbens	tissue	0.6
Locus coeruleus	tissue	0.6
Hippocampus	tissue	0.6	not detected
Hypothalamus	tissue	0.5
Bone marrow	tissue	0.5	not detected
Cervix	tissue	0.4	not detected
Choroid plexus	tissue	0.4
Prefrontal cortex	tissue	0.3
Cerebral cortex	tissue	0.3	not detected
Pons	tissue	0.3
Periaqueductal gray	tissue	0.3
Septum	tissue	0.3
Motor cortex	tissue	0.2
Basal ganglia	tissue	0.2	not detected
Amygdala	tissue	0.2
Cerebellum	tissue	0.2	not detected
Substantia nigra	tissue	0.2
Hippocampal formation	tissue	0.2
Entorhinal cortex	tissue	0.2
Ventral forebrain	tissue	0.2
Retrosplenial cortex	tissue	0.2
Insular cortex	tissue	0.2
Heart muscle	tissue	0.1	not detected
Epididymis	tissue	0.1	not detected
Putamen	tissue	0.1
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Placenta	tissue	0.1	not detected
Retrosplenial and cingulate cortex	tissue	0.1
Somatosensory cortex	tissue	0.1
Temporal cortex	tissue	0.1
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 184; highest nTPM — Ventral tegmental area (5.8), Median raphe nucleus (1.9), Pulvinar (1.7), Posterior thalamic nucleus (1.5), Ventral posteromedial thalamic nucleus (1.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LPO by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

21 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-4800-5P	97.22	65.91	324
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-6874-5P	95.73	64.94	545
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Functional genomics

gnomAD constraint: pLI 6.87e-25, LOEUF 1.23, missense Z 0.782 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000262290 — one region, missense o/e 0.96.

Literature-anchored findings (GeneRIF, showing 9)

• a functional LPO system exists in human airways and may contribute to airway host defense against infection (PMID:12626341)
• lactoperoxidase may play an important role in the metabolic events associated with Parkinson’s disease (PMID:15384204)
• 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)
• Splice variants may contribute to LPO molecular heterogeneity and its regulation by intracellular compartmental localization in respiratory epithelium. (PMID:19059195)
• Oral peroxidase activity as a marker of chronic alcohol abuse may help in the diagnosis of alcoholism. (PMID:23042278)
• establish urate as a likely physiological substrate for LPO that will influence host defense and give rise to reactive electrophilic metabolites (PMID:24928513)
• High intensity of caries is associated with increased levels of some salivary components - sIgA, histatin-5 and lactoperoxidase. (PMID:24974109)
• LPO mRNA was undetectable in the gastric mucosa. (PMID:27048452)
• The crystal structure of the complex of LPO with MZY showed that MZY bound to LPO in the substrate-binding site on the distal heme side. MZY was oriented in the substrate-binding site in such a way that the sulfur atom is at a distance of 2.58 A from the heme iron (PMID:28653416)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	epx	ENSDARG00000012535
mus_musculus	Lpo	ENSMUSG00000009356
rattus_norvegicus	Lpo	ENSRNOG00000008422
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), EPX (ENSG00000121053), PXDN (ENSG00000130508), PXDNL (ENSG00000147485)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923363) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 51 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
thin ventricular wall	1
abnormal intestinal mucosa morphology	1
abnormal choroid plexus morphology	1
abnormal medulla oblongata morphology	1
thick pulmonary interalveolar septum	1
abnormal body weight	1
abnormal lens morphology	1
increased inflammatory response	1
myocarditis	1
intestinal inflammation	1
liver inflammation	1
lung inflammation	1
blood vessel inflammation	1
pancreas inflammation	1
stomach inflammation	1
increased tumor incidence	1
increased sarcoma incidence	1
seizures	1
premature death	1
abnormal brain morphology	1
abnormal bronchiole morphology	1
glomerulonephritis	1
dilated cardiomyopathy	1
axonal dystrophy	1

+26 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bubalus bubalis	A5JUY8	99.4%	Diamond
Bos taurus	P80025	99.4%	Diamond
Ovis aries	P79208	97.0%	Diamond
Capra hircus	A0A452E9Y6	95.1%	Diamond
Oryctolagus cuniculus	O02768	90.9%	Diamond
Equus caballus	O19183	90.9%	Diamond
Cavia porcellus	P70682	90.2%	Diamond
Caenorhabditis briggsae	A8WQH2	87.3%	Diamond
Mesocricetus auratus	Q8R481	84.6%	Diamond
Gallus gallus	P27607	82.1%	Diamond
Xenopus tropicalis	A4IGL7	81.7%	Diamond
Canis lupus familiaris	Q8HYB7	74.2%	Diamond
Sus scrofa	P09933	73.3%	Diamond
Anopheles gambiae	Q7QH73	51.4%	Diamond
Anopheles albimanus	A0A1Y9G8H0	47.2%	Diamond
Lottia gigantea	B3A0Q8	46.3%	Diamond
Pinctada margaritifera	H2A0M7	36.6%	Diamond
Dictyostelium discoideum	Q6TMK4	33.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4736	ncRNA	100616220
MIR142HG	ncRNA	123466215
HSF5	protein-coding	124535
MIR142	ncRNA	406934
MPO	protein-coding	4353
RNF43	protein-coding	54894
SUPT4H1	protein-coding	6827
MTMR4	protein-coding	9110
TSPOAP1	protein-coding	9256
MKS1	protein-coding	54903
EPX	protein-coding	8288
TSPOAP1-AS1	ncRNA	100506779
OR4D2	protein-coding	124538

Protein

Protein identifiers

Lactoperoxidase — P22079 (reviewed: P22079)

Alternative names: Salivary peroxidase

All UniProt accessions (5): P22079, F5H386, H0Y3I2, J3KT11, J3QSD8

UniProt curated annotations — full annotation on UniProt →

Function. Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2). Also involved in the conversion of iodide (I(-)) into hypoiodite (IO(-)) in the presence of H2O2. Responsible for the inactivation of a wide range of micro-organisms and hence, important component of defense mechanism. Shows antibacterial properties against Pseudomonas aeruginosa. The lactoperoxidase-SCN(-)-H2O2 system shows antibacterial properties against Burkholderia cepacia and Haemophilus influenzae in vitro. Present in mammary and salivary gland secretions and may contribute to airway host defense against infection. May contribute to maintaining an appropriate H2O2 cellular level, therefore protecting cells from H2O2-caused injuries and inflammation.

Subcellular location. Secreted. Cytoplasm.

Tissue specificity. Mammary gland, milk and salivary gland. Found in bronchial submucosal glands.

Cofactor. Binds 1 Ca(2+) ion per heterodimer. Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.

Miscellaneous. Thiocyanate (SCN(-)) and hypothiocyanite (OSCN(-)) are bound in the distal heme cavity. The iodide ion (I(-)) occupies a position which is stabilized by the interactions with heme moiety, His-226, Arg-372 and Glu-375. Hydrogen peroxide is held between the heme iron and His-226.

Similarity. Belongs to the peroxidase family. XPO subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P22079-1	1	yes
P22079-2	2, V3

RefSeq proteins (2): NP_001153574, NP_006142* (*=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)

• 2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2 H2O (RHEA:56136)
• thiocyanate + H2O2 + H(+) = hypothiocyanous acid + H2O (RHEA:69416)
• iodide + H2O2 = hypoiodite + H2O (RHEA:69420)

UniProt features (35 total): binding site 8, sequence variant 7, disulfide bond 6, glycosylation site 4, modified residue 2, sequence conflict 2, signal peptide 1, propeptide 1, site 1, chain 1, splice variant 1, active site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22079-F1	92.43	0.80

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted secreted proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
372	transition state stabilizer
226	proton acceptor

Ligand- & substrate-binding residues (8)

Position	Role
375	heme b
468	heme b
225	heme b
227	Ca(2+)
301	Ca(2+)
303	Ca(2+)
305	Ca(2+)
307	Ca(2+)

Post-translational modifications (2)

Type	Positions
Phosphoserine	315
3’-nitrotyrosine	482

Disulfide bonds (6)

Type	Positions
Disulfide bond	132–145, 246–256, 250–274, 354–365, 573–630, 671–696

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	106, 212, 322, 358

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-8941413	Events associated with phagocytolytic activity of PMN cells	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1222556	ROS and RNS production in phagocytes	—

MSigDB gene sets: 82 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, CEBPB_01, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE, GOBP_SENSORY_PERCEPTION_OF_TASTE, WTGAAAT_UNKNOWN, GOBP_DETOXIFICATION, GGGNNTTTCC_NFKB_Q6_01, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOMF_ANTIOXIDANT_ACTIVITY

GO Biological Process (6): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), response to oxidative stress (GO:0006979), defense response to bacterium (GO:0042742), hydrogen peroxide catabolic process (GO:0042744), thiocyanate metabolic process (GO:0018969), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (6): peroxidase activity (GO:0004601), heme binding (GO:0020037), thiocyanate peroxidase activity (GO:0036393), metal ion binding (GO:0046872), lactoperoxidase activity (GO:0140825), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): extracellular region (GO:0005576), cytoplasm (GO:0005737), basolateral plasma membrane (GO:0016323), extracellular exosome (GO:0070062)

Reactome top-level categories

3 top-level categories:

Category	Pathways
ROS and RNS production in phagocytes	1
Innate Immune System	1
Immune System	1

GO top-level categories

21 GO namespaces:

Category	Terms
peroxidase activity	2
cellular anatomical structure	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
response to stress	1
defense response	1
response to bacterium	1
catabolic process	1
hydrogen peroxide metabolic process	1
sulfur compound metabolic process	1
cellular detoxification	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
tetrapyrrole binding	1
thiocyanate metabolic process	1
cation binding	1
catalytic activity	1
intracellular anatomical structure	1
basal plasma membrane	1
plasma membrane region	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
defense response to bacterium	BP	direct assay
detection of chemical stimulus involved in sensory perception of bitter taste	BP	direct assay
basolateral plasma membrane	CC	direct assay
extracellular exosome	CC	high-throughput assay
peroxidase activity	MF	direct assay
thiocyanate peroxidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 522 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPO	LTF	P02788	796
LPO	LALBA	P00709	796
LPO	CSN3	P07498	569
LPO	STATH	P02808	537
LPO	CSN2	P05814	517
LPO	CSN1S1	P47710	486
LPO	HTN3	P15516	486
LPO	ALB	P02768	459
LPO	PIGR	P01833	457
LPO	DUOXA1	Q1HG43	448
LPO	HTN1	P15515	425
LPO	BPIFA2	Q96DR5	406
LPO	FUT5	Q11128	398
LPO	CST4	P01036	394
LPO	AMY1B	P04745	389

IntAct

BioGRID (9 interactions; top human partners by supporting records): DDX31 (Affinity Capture-MS; 2 records), HEXB (Affinity Capture-MS), HTN3 (Affinity Capture-MS), NR3C1 (Proximity Label-MS), TIMM10 (Affinity Capture-MS), YTHDC1 (Affinity Capture-RNA), ZC3HAV1 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for LPO: 126 ClinVar records (1 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	4
Benign	8

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1710927	GRCh37/hg19 17q22(chr17:55043662-56728123)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore LPO’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 1,317):

Position(s)	Effect	Δscore	Sites
17:58238740	donor_loss	1.0000	2
17:58250413–58250414	acceptor_loss	1.0000	6
17:58250551	donor_gain	1.0000
17:58250636	donor_gain	1.0000
17:58264990	donor_gain	1.0000
17:58266147–58266148	acceptor_gain	1.0000	2
17:58266151–58266152	acceptor_loss	1.0000	6
17:58266327–58266328	donor_loss	1.0000	3
17:58267785–58267786	acceptor_loss	1.0000	5
17:58268013	donor_gain	1.0000

AlphaMissense

1,126 missense substitutions predicted likely pathogenic (of 4,655 scored), across 323 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D549	8	0.953	0.969
D643	8	0.922	0.962
H390	8	0.885	0.927
F653	8	0.878	0.954
D560	8	0.875	0.969
D305	8	0.872	0.922
D608	8	0.848	0.935
H468	8	0.847	0.918
D370	8	0.840	0.934
F460	8	0.822	0.961
D227	8	0.801	0.908
D265	8	0.711	0.793
C365	7	0.962	0.977
C354	7	0.960	0.981
C671	7	0.939	0.973
C573	7	0.929	0.962
F539	7	0.922	0.956
C274	7	0.915	0.964
C696	7	0.901	0.939
W569	7	0.900	0.976

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:150205 | disease phenotypes: MIM:104300, MIM:254600

GenCC curated gene-disease

Mondo (2): Alzheimer disease type 1 (MONDO:0007088), myeloperoxidase deficiency (MONDO:0009694)

Orphanet (1): Myeloperoxidase deficiency (Orphanet:2587)

GWAS associations

9 associations:

Study	Trait	p-value
GCST90002379_83	Basophil count	4e-28
GCST006585_1877	Blood protein levels	8e-25
GCST90002394_398	Monocyte percentage of white cells	3e-19
GCST90002380_102	Basophil percentage of white cells	4e-18
GCST004618_42	White blood cell count (basophil)	1e-10
GCST003265_350	Post bronchodilator FEV1/FVC ratio in COPD	1e-6
GCST003265_15	Post bronchodilator FEV1/FVC ratio in COPD	2e-6
GCST003265_84	Post bronchodilator FEV1/FVC ratio in COPD	2e-6
GCST003263_117	Post bronchodilator FEV1 in COPD	4e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C536594	Alzheimer disease type 1 *(supp.)*
C562864	Myeloperoxidase Deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5898 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,782 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL508102	CARBIMAZOLE	4	3,791
CHEMBL1515	METHIMAZOLE	4	19,072
CHEMBL1518	PROPYLTHIOURACIL	4	15,154
CHEMBL1330588	METHYLTHIOURACIL	2	1,765

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

21 measured of 25 human assays (26 total across all organisms); most potent 21 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(1,3-benzodioxol-5-yl)-6-methyl-2-pyridin-3-ylimidazo[1,2-a]pyridin-3-amine	IC50	13 nM	US-20240408072: COMPOSITION FOR PREVENTING OR TREATING GRAVES’ DISEASE COMPRISING COMPOUND CONTAINING AN IMIDAZOPYRIDINE STRUCTURE AS ACTIVE INGREDIENT
4-[3-(1,3-benzodioxol-5-ylamino)-7-methylimidazo[1,2-a]pyridin-2-yl]phenol	IC50	16 nM	US-20240408072: COMPOSITION FOR PREVENTING OR TREATING GRAVES’ DISEASE COMPRISING COMPOUND CONTAINING AN IMIDAZOPYRIDINE STRUCTURE AS ACTIVE INGREDIENT
N-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)-7-methylimidazo[1,2-a]pyridin-3-amine	IC50	20 nM	US-20240408072: COMPOSITION FOR PREVENTING OR TREATING GRAVES’ DISEASE COMPRISING COMPOUND CONTAINING AN IMIDAZOPYRIDINE STRUCTURE AS ACTIVE INGREDIENT
7-[(2-fluorophenyl)methylsulfanyl]-2H-triazolo[4,5-b]pyridin-5-amine	IC50	22 nM	US-10981879: Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase
CHEMBL4747269	IC50	92 nM
N-[5-(5-methoxy-1,2-dimethylindol-3-yl)-1H-imidazol-2-yl]-2,2-dimethyl-5-oxooxolane-3-carboxamide	IC50	130 nM	US-20240408072: COMPOSITION FOR PREVENTING OR TREATING GRAVES’ DISEASE COMPRISING COMPOUND CONTAINING AN IMIDAZOPYRIDINE STRUCTURE AS ACTIVE INGREDIENT
CHEMBL4790231	IC50	360 nM
CHEMBL5517779	IC50	590 nM
CHEMBL5555319	IC50	2200 nM
CHEMBL5560226	IC50	5500 nM
CHEMBL5557885	IC50	7300 nM
ethyl 2,3-dihydro-3-methyl-2-selenoxoimidazole-1-carboxylate	IC50	10100 nM
methyl 3-methyl-2-thioxo-2,3-dihydro-1H-imidazole-1-carboxylate	IC50	10700 nM
methyl 3-ethyl-2-thioxo-2,3-dihydro-1H-imidazole-1-carboxylate	IC50	19600 nM
methyl 3-methyl-2-selenoxo-2,3-dihydro-1H-imidazole-1-carboxylate	IC50	19700 nM
ethyl 3-ethyl-2-thioxo-2,3-dihydro-1H-imidazole-1-carboxylate	IC50	20500 nM
ethyl 3-ethyl-2-selenoxo-2,3-dihydro-1H-imidazole-1-carboxylate	IC50	21300 nM
CHEMBL5557030	IC50	23100 nM
methyl 3-ethyl-2-selenoxo-2,3-dihydro-1H-imidazole-1-carboxylate	IC50	25300 nM
CHEMBL5558431	IC50	38700 nM
CHEMBL5561937	IC50	137000 nM

ChEMBL bioactivities

8 potent at pChembl≥5 of 19 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.29	IC50	510	nM	METHIMAZOLE
6.23	IC50	590	nM	CHEMBL5517779
5.83	IC50	1490	nM	METHYLTHIOURACIL
5.66	IC50	2200	nM	CHEMBL5555319
5.26	IC50	5500	nM	CHEMBL5560226
5.14	IC50	7300	nM	CHEMBL5557885
5.12	IC50	7520	nM	PROPYLTHIOURACIL
5.00	IC50	1.01e+04	nM	CHEMBL457523

PubChem BioAssay actives

7 with measured affinity, of 32 total; 7 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
Methimazole	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	0.5100	uM
1,3-dimethylimidazole-2-selone	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	0.5900	uM
6-methyl-2-sulfanylidene-1H-pyrimidin-4-one	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	1.4900	uM
1-[(3-methoxyphenyl)methyl]-3-methylimidazole-2-selone	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	2.2000	uM
1,3-bis[(3-methoxyphenyl)methyl]imidazole-2-selone	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	5.5000	uM
9989524	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	7.3000	uM
Propylthiouracil	2076731: Inhibition of LPO (unknown origin)-mediated L-tyrosine nitration incubated for 20 mins in presence of H2O2 and sodium nitrite by RP-HPLC analysis	ic50	7.5200	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Paraquat	decreases reaction, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
naringenin	increases expression, decreases reaction	1
fenvalerate	decreases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
cerous chloride	affects cotreatment, increases expression	1
lanthanum chloride	affects cotreatment, increases expression	1
benzidine	increases metabolic processing	1
coumarin	decreases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
fumonisin B1	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
bisphenol AF	decreases expression	1
Gabapentin	decreases expression	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	decreases expression	1
Colchicine	decreases expression	1
Diethylstilbestrol	decreases expression	1
Endosulfan	decreases expression	1
Fluorouracil	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases metabolic processing	1
Hydroxyurea	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Medroxyprogesterone	affects cotreatment, affects expression	1
Nitrites	affects cotreatment, increases metabolic processing	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4263009	Binding	Inhibition of recombinant human LPO isoform-1 (26 to 712 residues) expressed in baculovirus infected insect cells assessed as reduction in H2O2-catalyzed 3,5-iodo tyrosine formation using 3-iodotyrosine and potassium iodide preincubated for	Triazolopyrimidines identified as reversible myeloperoxidase inhibitors. — *Medchemcomm*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

23 trials:

NCT	Phase	Status	Title
NCT04520308	Phase 4	UNKNOWN	An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis
NCT02380573	Phase 2	COMPLETED	Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer’s Disease
NCT03806478	Phase 2	UNKNOWN	Study of APH-1105 in Patients With Mild to Moderate Alzheimer’s Disease
NCT07011706	Phase 2	ACTIVE_NOT_RECRUITING	ATI-045 Versus Placebo in Patients With Moderate-to-Severe Atopic Dermatitis
NCT07252440	Phase 2	RECRUITING	A Study to Evaluate the Efficacy and Safety of TTYP01 Tablets in Early Symptomatic Alzheimer’s Disease
NCT03932916	Phase 1	COMPLETED	Safety and Pharmacokinetic of Donepezil Pamoate in Healthy Subjects
NCT06593626	Phase 1	COMPLETED	A Phase I Clinical Study on the Safety and Pharmacokinetics of [18F]Florbetazine Injection
NCT07693738	Phase 1	RECRUITING	A Phase I Study of SSGJ-716 in Healthy Adults and Participants With Moderate-to-Severe Atopic Dermatitis
NCT05984784	Phase 1/2	TERMINATED	A Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of IMG-007 in Adults With Atopic Dermatitis (AD)
NCT01733355	Early Phase 1	TERMINATED	A Phase 0, Open Label, Multi-center Exploratory and Safety Study of [F-18]T807
NCT05469009	Early Phase 1	ACTIVE_NOT_RECRUITING	Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer’s Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
NCT01190904	Not specified	COMPLETED	Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes
NCT02273895	Not specified	COMPLETED	The Use of EEG in Alzheimer’s Disease, With and Without Scopolamine - A Pilot Study
NCT04100889	Not specified	WITHDRAWN	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Alzheimer’s Disease
NCT05078944	Not specified	COMPLETED	Progress of Mild Alzheimer’s Disease in Participants on Acupuncture Versus Sham Acupuncture
NCT05372458	Not specified	UNKNOWN	The Mechanism Study of Diabetic Pancreatic Amyloid Deposition on Cognitive Dysfunction in Alzheimer’s Disease
NCT05637801	Not specified	COMPLETED	A Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (HOPE Study)
NCT06039267	Not specified	COMPLETED	Brain Health & the Microbiome
NCT06155201	Not specified	UNKNOWN	Development and Application of Intelligent Diagnosis and Treatment Norms for Children and Adolescents With Mental Disorders
NCT06245031	Not specified	ENROLLING_BY_INVITATION	Extension to a Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (OLE Hope Study, CA-0015)
NCT06335836	Not specified	RECRUITING	The Effects of Social Isolation and Social Interaction on the Risk of Dementia Progression and Brain Function in SCD (Subjective Cognitive Decline, SCD)
NCT07100470	Not specified	NOT_YET_RECRUITING	Metabolic Characterization of Alzheimer’s Disease and Frontotemporal Dementia by 23Na-MRI and FDG-PET
NCT07672977	Not specified	ENROLLING_BY_INVITATION	Home-Based Closed-Loop Auditory Stimulation to Enhance Slow-Wave Activity in MCI Due to Alzheimer’s Disease: A Proof-of-Concept Study

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LPO across ~30M SureChEMBL compounds — explore on Sugi Predict.