MPEG1

Summary

MPEG1 (macrophage expressed 1, HGNC:29619) is a protein-coding gene on chromosome 11q12.1, encoding Macrophage-expressed gene 1 protein (Q2M385). Pore-forming protein involved in both innate and adaptive immunity.

Enables wide pore channel activity. Involved in defense response to Gram-negative bacterium and defense response to Gram-positive bacterium. Located in cytoplasmic vesicle. Is active in phagolysosome membrane. Implicated in primary immunodeficiency disease.

Source: NCBI Gene 219972 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 77 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 147 total — 2 pathogenic
• Phenotypes (HPO): 10
• Druggable target: yes
• MANE Select transcript: NM_001039396

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29619
Approved symbol	MPEG1
Name	macrophage expressed 1
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	P2, MPS-1, MPG1
Ensembl gene	ENSG00000197629
Ensembl biotype	protein_coding
OMIM	610390
Entrez	219972

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000361050, ENST00000877842

RefSeq mRNA: 1 — MANE Select: NM_001039396 NM_001039396

CCDS: CCDS41650

Canonical transcript exons

ENST00000361050 — 1 exons

Exon	Start	End
ENSE00001412014	59208510	59212927

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 99.46.

FANTOM5 (CAGE): breadth broad, TPM avg 36.8665 / max 2184.2056, expressed in 462 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119858	35.6002	462
119848	0.4490	131
119852	0.1619	78
119854	0.1324	70
119850	0.1261	73
119856	0.0967	60
119849	0.0868	51
119853	0.0834	59
119851	0.0767	42
119855	0.0534	40

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.46	gold quality
leukocyte	CL:0000738	99.43	gold quality
ileal mucosa	UBERON:0000331	98.80	gold quality
granulocyte	CL:0000094	98.58	gold quality
vermiform appendix	UBERON:0001154	98.05	gold quality
spleen	UBERON:0002106	96.62	gold quality
blood	UBERON:0000178	96.25	gold quality
lymph node	UBERON:0000029	94.12	gold quality
trabecular bone tissue	UBERON:0002483	93.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.59	gold quality
gall bladder	UBERON:0002110	93.01	gold quality
palpebral conjunctiva	UBERON:0001812	92.74	gold quality
jejunal mucosa	UBERON:0000399	92.65	gold quality
rectum	UBERON:0001052	92.19	gold quality
bone marrow	UBERON:0002371	91.59	gold quality
bone marrow cell	CL:0002092	91.49	gold quality
epithelium of nasopharynx	UBERON:0001951	90.76	gold quality
decidua	UBERON:0002450	90.49	gold quality
synovial joint	UBERON:0002217	90.30	gold quality
caecum	UBERON:0001153	90.28	gold quality
duodenum	UBERON:0002114	89.26	gold quality
layer of synovial tissue	UBERON:0007616	89.17	gold quality
superficial temporal artery	UBERON:0001614	88.90	gold quality
smooth muscle tissue	UBERON:0001135	88.54	gold quality
colonic mucosa	UBERON:0000317	87.79	gold quality
lower lobe of lung	UBERON:0008949	87.41	gold quality
parietal pleura	UBERON:0002400	86.89	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.77	silver quality
skin of hip	UBERON:0001554	86.62	gold quality
upper arm skin	UBERON:0004263	86.40	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	1507.54
E-GEOD-150728	yes	1090.44
E-MTAB-6678	yes	980.73
E-MTAB-9067	yes	701.81
E-GEOD-75688	yes	594.22
E-GEOD-149689	yes	524.07
E-MTAB-9221	yes	378.72
E-CURD-122	yes	70.15
E-CURD-46	yes	33.78
E-MTAB-10553	yes	33.04
E-MTAB-6701	yes	30.37
E-CURD-112	yes	22.96
E-ANND-3	yes	21.71
E-HCAD-1	yes	19.84
E-HCAD-9	yes	17.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting MPEG1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-12124	99.68	69.17	2700

Literature-anchored findings (GeneRIF, showing 7)

• Knockdown of perforin-2 in macrophages did not alter the invasion of host cells but did result in chlamydial growth that closely mirrored that detected in HeLa cells. (PMID:23753625)
• the impact of Perforin-2/macrophage-expressed protein 1 from the earliest multicellular organisms to modern vertebrates, as well as review the development of other membrane attack complexes of complement and Perforin domain member proteins (PMID:26307549)
• Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria. (PMID:26418746)
• these data provide the evidence that membrane-bound and secretory isoforms of perforin-2 are present in human macrophages and may play important roles in immune defense (PMID:28705375)
• Macrophage-specific protein perforin-2 is associated with poor neurological recovery and reduced survival after sudden cardiac arrest. (PMID:32828820)
• Breaching the Bacterial Envelope: The Pivotal Role of Perforin-2 (MPEG1) Within Phagocytes. (PMID:33692780)
• Intracellular Staphylococcus aureus triggers pyroptosis and contributes to inhibition of healing due to perforin-2 suppression. (PMID:34730110)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpeg1.2	ENSDARG00000043093
danio_rerio	mpeg1.1	ENSDARG00000055290
danio_rerio	mpeg1.3	ENSDARG00000078569
mus_musculus	Pfpl	ENSMUSG00000040065
mus_musculus	Mpeg1	ENSMUSG00000046805
rattus_norvegicus	Pfpl	ENSRNOG00000060431
rattus_norvegicus	Mpeg1	ENSRNOG00000063244

Protein

Protein identifiers

Macrophage-expressed gene 1 protein — Q2M385 (reviewed: Q2M385)

Alternative names: Perforin-2

All UniProt accessions (1): Q2M385

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming protein involved in both innate and adaptive immunity. Plays a central role in antigen cross-presentation in dendritic cells by forming a pore in antigen-containing compartments, thereby promoting delivery of antigens for cross-presentation. Also involved in innate immune response following bacterial infection; shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria. Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol. Required for the antibacterial activity of reactive oxygen species and nitric oxide. Pore-forming protein that plays a central role in antigen cross-presentation in dendritic cells by mediating delivery of antigens for cross-presentation. Dendritic cells bridge innate and adaptive immunity by capturing exogenous antigens on MHC class-I molecules and presenting them to naive CD8(+) T-cells. Acts by forming a pore in antigen-containing compartments, promoting the release of antigens into the cytosol, enabling generation of MHCI:peptide complexes and T-cell priming.

Subunit / interactions. Homooligomer. Predominantly forms a homooligomeric arc-shaped pore complex instead of complete rings of 16 subunits.

Subcellular location. Cytoplasmic vesicle membrane Cytoplasmic vesicle. Phagosome membrane Secreted.

Tissue specificity. Expressed constitutively in a variety of cell types including macrophages, natural killer cells, neutrophils, keratinocytes and monocytes. In skin, expressed in both hematopoietic and non-hematopoietic cells with expression detected in a variety of cell types including keratinocytes, fibroblasts and endothelial cells.

Post-translational modifications. Proteolytically processed in two steps to generate the Macrophage-expressed gene 1 protein, processed form: cleaved by trypsin in proximity of the helical transmembrane domain releases the ectodomain into the lysosomal lumen to orient the pore-forming domain toward the endogenous membranes, and processed by the asparagine endopeptidase (LGMN). Monoubiquitinated in response to bacterial infection; ubiquitination is required for vesicular localization and antibacterial activity and can be blocked by bacterial cell cycle inhibiting factor (cif).

Disease relevance. Immunodeficiency 77 (IMD77) [MIM:619223] An autosomal dominant disorder characterized by recurrent, persistent bacterial and fungal infections with multiple unusual organisms. Skin and pulmonary infections are the most common. Patient macrophages show impaired killing of intracellular bacteria and organisms, including non-tubercular mycobacteria, Pseudomonas, Candida, and Aspergillus. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Forms arc- and ring-shaped pre-pores on top of the membrane at neutral to slightly acidic pH conditions and converts to pores upon acidification. Undergoes transition from the pre-pore to the pore in a processive clockwise hand-over-hand process. In the pore state, 2 alpha-helical regions refold into transmembrane hairpins (TMH1 and TMH2) in each protomer that form in the ensemble complex giant beta-barrel transmembrane pores.

Domain organisation. The MACPF domain includes the central machinery of pore formation: acidification causes a significant structural rearrangement, leading to oligomerization and deployment of the transmembrane beta-strands (named TMH1 and TMH2) that enter the membrane as amphipathic beta-hairpins. The P2 region contains beta-hairpins to interact with target membranes.

Induction. By wounding; increased levels are observed in hematopoietic cells 48 hours after wounding. Following wounding, repressed by infection with S.aureus. Isoform 1: By lipopolysaccharide and TNF. Isoform 2: By lipopolysaccharide and TNF.

Miscellaneous. Lacks the C-terminal transmembrane domain.

Similarity. Belongs to the MPEG1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2M385-1	1, PRF2a	yes
Q2M385-2	2, PRF2b

RefSeq proteins (1): NP_001034485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020864	MACPF	Domain
IPR039707	MPEG1	Family

Pfam: PF01823

UniProt features (91 total): strand 35, helix 13, turn 11, sequence variant 8, disulfide bond 7, transmembrane region 5, site 4, glycosylation site 3, chain 2, signal peptide 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6U2J	ELECTRON MICROSCOPY	2.37
6U2L	ELECTRON MICROSCOPY	2.83
6U2K	ELECTRON MICROSCOPY	2.93
6U23	ELECTRON MICROSCOPY	3.49
6U2W	ELECTRON MICROSCOPY	3.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M385-F1	83.22	0.54

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 (4): 352–353 (cleavage; by lgmn); 357–358 (cleavage; by lgmn); 359–360 (cleavage; by lgmn); 631–632 (cleavage; by trypsin)

Disulfide bonds (7): 34–70, 350–369, 385–397, 435–449, 439–445, 534–572, 557–577

Glycosylation sites (3): 185, 269, 375

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOCC_VACUOLAR_MEMBRANE, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, RAMALHO_STEMNESS_DN, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, STEARMAN_TUMOR_FIELD_EFFECT_UP, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_ADAPTIVE_IMMUNE_RESPONSE, MORI_PRE_BI_LYMPHOCYTE_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_EXOGENOUS_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I

GO Biological Process (12): adaptive immune response (GO:0002250), dendritic cell antigen processing and presentation (GO:0002468), antigen processing and presentation of exogenous peptide antigen (GO:0002478), antigen processing and presentation of exogenous peptide antigen via MHC class I (GO:0042590), defense response to bacterium (GO:0042742), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), antibacterial innate immune response (GO:0140367), immune system process (GO:0002376), antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent (GO:0002479), innate immune response (GO:0045087), transmembrane transport (GO:0055085)

GO Molecular Function (1): wide pore channel activity (GO:0022829)

GO Cellular Component (7): extracellular region (GO:0005576), phagocytic vesicle membrane (GO:0030670), cytoplasmic vesicle (GO:0031410), phagocytic vesicle (GO:0045335), phagolysosome membrane (GO:0061474), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	3
immune response	2
cellular anatomical structure	2
antigen processing and presentation	1
antigen processing and presentation of exogenous antigen	1
antigen processing and presentation of peptide antigen	1
antigen processing and presentation of peptide antigen via MHC class I	1
antigen processing and presentation of exogenous peptide antigen	1
defense response	1
response to bacterium	1
innate immune response	1
biological_process	1
antigen processing and presentation of exogenous peptide antigen via MHC class I	1
defense response to symbiont	1
transport	1
cellular process	1
channel activity	1
endocytic vesicle membrane	1
phagocytic vesicle	1
cytoplasm	1
intracellular vesicle	1
endocytic vesicle	1
lysosomal membrane	1
phagocytic vesicle membrane	1
phagolysosome	1
vesicle membrane	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPEG1	PRF1	P14222	808
MPEG1	MFAP4	P55083	571
MPEG1	LYZ	P00695	570
MPEG1	LCP1	P13796	531
MPEG1	SPACA3	Q8IXA5	522
MPEG1	LGALS4	P56470	474
MPEG1	CSF3R	Q99062	474
MPEG1	NTSR1	P30989	446
MPEG1	SPI1	P17947	404
MPEG1	PHB1	P35232	371
MPEG1	PHB2	Q99623	353
MPEG1	IRF8	Q02556	335
MPEG1	CSF1R	P07333	335
MPEG1	MPO	P05164	315
MPEG1	IL1B	P01584	308

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TNS2	MPEG1	psi-mi:“MI:0915”(physical association)	0.370
RIN3	MPEG1	psi-mi:“MI:0915”(physical association)	0.370
accC	MPEG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): MPEG1 (Two-hybrid), MPEG1 (Two-hybrid), MPEG1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS97, A1L314, D3YXF5, E7F0Z8, O75339, P02748, P06682, P06683, P07357, P07358, P10643, P10820, P35763, P48747, P48770, P51578, P55314, P79755, P98136, P98137, Q2KJC3, Q2M385, Q3MHN2, Q3V5L5, Q5RBP9, Q62930, Q64663, Q66K08, Q66S13, Q66S17, Q66S21, Q66S25, Q6UX71, Q765H6, Q8BG22, Q8BH35, Q8K182, Q8L612, Q8N2E2, Q90X85

Diamond homologs: A1L314, Q2KJC3, Q2M385, Q5RBP9, Q9WV57

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHEK2	“up-regulates activity”	MPEG1	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	124
Likely benign	16
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1035588	NM_001039396.2(MPEG1):c.1192C>T (p.Gln398Ter)	Pathogenic
2505512	NM_001039396.2(MPEG1):c.973C>T (p.Pro325Ser)	Pathogenic

SpliceAI

24 predictions. Top by Δscore:

Variant	Effect	Δscore
11:59209294:T:TC	acceptor_gain	0.8500
11:59208813:C:CT	acceptor_gain	0.8300
11:59209296:G:C	acceptor_gain	0.5800
11:59211872:TTGAC:T	donor_gain	0.5800
11:59208813:C:T	acceptor_gain	0.5100
11:59209290:T:TG	acceptor_gain	0.4700
11:59209524:T:A	acceptor_gain	0.4600
11:59209294:T:C	acceptor_gain	0.4100
11:59209326:C:G	acceptor_gain	0.4100
11:59209291:T:A	acceptor_gain	0.3900
11:59209523:C:A	acceptor_gain	0.3700
11:59209325:T:TG	acceptor_gain	0.3600
11:59211871:TTTGA:T	donor_gain	0.3300
11:59210180:C:T	acceptor_gain	0.3200
11:59209522:ACT:A	acceptor_gain	0.3000
11:59209301:C:CT	acceptor_gain	0.2900
11:59209296:G:GC	acceptor_gain	0.2800
11:59210622:T:C	donor_gain	0.2700
11:59210299:T:C	acceptor_gain	0.2500
11:59211623:C:CT	acceptor_gain	0.2400
11:59209290:T:C	acceptor_gain	0.2300
11:59210299:T:TC	acceptor_gain	0.2200
11:59212407:T:TA	donor_gain	0.2100
11:59210618:C:T	donor_gain	0.2000

AlphaMissense

4703 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:59211817:C:G	C350S	0.993
11:59211818:A:T	C350S	0.993
11:59211267:G:C	S533R	0.989
11:59211267:G:T	S533R	0.989
11:59211269:T:G	S533R	0.989
11:59211329:A:G	C513R	0.988
11:59211473:A:G	C465R	0.988
11:59211472:C:G	C465S	0.987
11:59211473:A:T	C465S	0.987
11:59210976:C:A	W630C	0.986
11:59210976:C:G	W630C	0.986
11:59211818:A:G	C350R	0.986
11:59211135:G:C	C577W	0.985
11:59211136:C:T	C577Y	0.985
11:59211377:A:G	C497R	0.985
11:59211399:G:C	N489K	0.985
11:59211399:G:T	N489K	0.985
11:59211136:C:G	C577S	0.984
11:59211137:A:T	C577S	0.984
11:59211654:A:C	N404K	0.984
11:59211654:A:T	N404K	0.984
11:59211197:A:G	C557R	0.983
11:59211137:A:G	C577R	0.982
11:59211196:C:G	C557S	0.982
11:59211197:A:T	C557S	0.982
11:59211328:C:G	C513S	0.982
11:59211329:A:T	C513S	0.982
11:59211471:A:C	C465W	0.982
11:59211328:C:T	C513Y	0.981
11:59211476:A:G	W464R	0.980

dbSNP variants (sampled 300 via entrez): RS1001207587 (11:59209523 C>G), RS1001973456 (11:59208620 A>G), RS1003761457 (11:59210141 C>T), RS1004091080 (11:59214156 C>T), RS1004174771 (11:59212959 C>T), RS1004608171 (11:59209612 G>GA), RS1004935294 (11:59209779 G>A), RS1005043999 (11:59209946 G>GT), RS1005212958 (11:59212932 T>C), RS1005312122 (11:59209490 C>G), RS1005435726 (11:59213973 C>A), RS1005683762 (11:59208290 A>C), RS1006321194 (11:59208557 G>A), RS1006700452 (11:59208333 C>T), RS1006765656 (11:59208834 G>A)

Disease associations

OMIM: gene MIM:610390 | disease phenotypes: MIM:619223, MIM:608644

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 77	Strong	Autosomal dominant

Mondo (3): immunodeficiency 77 (MONDO:0030973), primary ciliary dyskinesia 3 (MONDO:0012085), Castleman-Kojima disease (MONDO:0018702)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), TAFRO syndrome (Orphanet:457077)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0002110	Bronchiectasis
HP:0002578	Gastroparesis
HP:0003581	Adult onset
HP:0006510	Chronic pulmonary obstruction
HP:0008619	Bilateral sensorineural hearing impairment
HP:0011110	Recurrent tonsillitis
HP:0031292	Cutaneous abscess
HP:0032261	Nontuberculous mycobacterial pulmonary infection
HP:0100658	Cellulitis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006364_1	Hepatitis B surface antigen seroclearance in chronic hepatitis B infection	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009345	Hepatitis B virus surface antigen seropositivity

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535278	Primary ciliary dyskinesia, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3414409 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

17 potent at pChembl≥5 of 17 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.68	IC50	210	nM	EMBELIN
6.10	IC50	800	nM	CHEMBL221598
6.05	IC50	900	nM	Rapanone
6.00	IC50	1000	nM	CHEMBL3416163
5.80	IC50	1600	nM	CHEMBL3416165
5.75	IC50	1800	nM	CHEMBL3416348
5.68	IC50	2100	nM	CHEMBL462998
5.66	IC50	2200	nM	CHEMBL29097
5.51	IC50	3100	nM	CHEMBL3416164
5.36	IC50	4400	nM	CHEMBL3416349
5.33	IC50	4700	nM	CHEMBL3416347
5.24	IC50	5800	nM	CHEMBL3416173
5.21	IC50	6100	nM	Sorgoleone-364
5.14	IC50	7200	nM	CHEMBL3416350
5.04	IC50	9100	nM	5-O-METHYLEMBELIN
5.03	IC50	9300	nM	CHEMBL3416174

PubChem BioAssay actives

17 with measured affinity, of 83 total; 16 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
2,5-dihydroxy-3-undecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	0.2100	uM
2,5-dihydroxy-3-octylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	0.8000	uM
2,5-dihydroxy-3-tridecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	0.9000	uM
3-decyl-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	1.0000	uM
2,5-dihydroxy-3-tetradecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	1.6000	uM
2,5-dimethoxy-3-tridecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	1.8000	uM
2,5-dihydroxy-3-pentadecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	2.1000	uM
3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-propan-2-ylindol-2-yl]-2,2-dimethylpropanoic acid	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	2.2000	uM
3-dodecyl-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	3.1000	uM
2,5-dimethoxy-3-tetradecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	4.4000	uM
3-dodecyl-2,5-dimethoxycyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	4.7000	uM
3-dodecyl-2-hydroxy-5-methoxycyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	5.8000	uM
2-hydroxy-5-methoxy-3-tridecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	6.1000	uM
2,5-dimethoxy-3-pentadecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	7.2000	uM
2-hydroxy-5-methoxy-3-undecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	9.1000	uM
2-hydroxy-5-methoxy-3-pentadecylcyclohexa-2,5-diene-1,4-dione	1201316: Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	ic50	9.3000	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, affects expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nickel	increases expression	2
sulforaphane	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Lead	decreases expression	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3420871	Binding	Inhibition of mPGES1 in IL-1beta stimulated human A549 cell microsomal membranes assessed as reduction in PGE2 synthase activity after 15 mins using PGH2 substrate by RP-HPLC method	Novel series of benzoquinones with high potency against 5-lipoxygenase in human polymorphonuclear leukocytes. — Eur J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.