MASP2

Summary

MASP2 (MBL associated serine protease 2, HGNC:6902) is a protein-coding gene on chromosome 1p36.22, encoding Mannan-binding lectin serine protease 2 (O00187). Precursor of a serum protease that activates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 10747 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency due to MASP-2 deficiency (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 204 total — 3 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_006610

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6902
Approved symbol	MASP2
Name	MBL associated serine protease 2
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	Map19, sMAP, MAP-2
Ensembl gene	ENSG00000009724
Ensembl biotype	protein_coding
OMIM	605102
Entrez	10747

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000400897, ENST00000400898, ENST00000478645, ENST00000480221, ENST00000699927, ENST00000699958, ENST00000700088, ENST00000700089, ENST00000700090, ENST00000700091, ENST00000700092, ENST00000700093, ENST00000700094, ENST00000700095, ENST00000700096, ENST00000700097, ENST00000700098, ENST00000860325, ENST00000860326, ENST00000860327, ENST00000860328, ENST00000860329

RefSeq mRNA: 2 — MANE Select: NM_006610 NM_006610, NM_139208

CCDS: CCDS123, CCDS124

Canonical transcript exons

ENST00000400897 — 11 exons

Exon	Start	End
ENSE00000472123	11030176	11030250
ENSE00000743084	11030748	11030882
ENSE00000743085	11034828	11034906
ENSE00000818830	11026523	11027648
ENSE00001833377	11047203	11047239
ENSE00003978087	11045408	11045539
ENSE00003978088	11042875	11043022
ENSE00003978089	11037693	11037811
ENSE00003978803	11043339	11043535
ENSE00003979426	11046556	11046733
ENSE00003979428	11046891	11047119

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 98.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3725 / max 622.2500, expressed in 21 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10279	1.3262	19
10277	0.0190	7
10278	0.0178	8
10280	0.0095	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.99	gold quality
liver	UBERON:0002107	96.35	gold quality
cerebellar hemisphere	UBERON:0002245	78.23	gold quality
cerebellar cortex	UBERON:0002129	78.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.94	gold quality
pancreatic ductal cell	CL:0002079	75.68	silver quality
diaphragm	UBERON:0001103	75.18	gold quality
cerebellum	UBERON:0002037	74.74	gold quality
left uterine tube	UBERON:0001303	72.23	gold quality
monocyte	CL:0000576	72.14	gold quality
muscle of leg	UBERON:0001383	71.98	gold quality
mononuclear cell	CL:0000842	71.94	gold quality
gastrocnemius	UBERON:0001388	71.94	gold quality
skin of leg	UBERON:0001511	71.73	gold quality
tibial nerve	UBERON:0001323	71.60	gold quality
leukocyte	CL:0000738	71.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.33	gold quality
mucosa of stomach	UBERON:0001199	71.32	gold quality
right ovary	UBERON:0002118	70.98	gold quality
skin of abdomen	UBERON:0001416	70.82	gold quality
tibial artery	UBERON:0007610	70.75	gold quality
popliteal artery	UBERON:0002250	70.72	gold quality
body of uterus	UBERON:0009853	70.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.66	gold quality
right lung	UBERON:0002167	70.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.57	gold quality
lower esophagus	UBERON:0013473	70.53	gold quality
tendon of biceps brachii	UBERON:0008188	70.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.45	gold quality
transverse colon	UBERON:0001157	70.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	30.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

33 targeting MASP2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-4676-5P	97.54	65.29	715
HSA-MIR-575	97.54	65.18	718
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-937-5P	97.43	68.39	667
HSA-MIR-8081	96.42	67.75	738

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The interaction of recombinant MASP2, its N-terminal complement modules, and MBL-associated protein 19 with L-ficolin/p35 has been characterized by surface plasmon resonance spectroscopy. (PMID:12421953)
• Results describe the x-ray structure of human mannan-binding lectin-associated protein 19 (MAp19), and identify the residues involved in the interaction of MAp19 with mannan-binding lectin and L-ficolin. (PMID:15117939)
• MASP-2 concentration in serum proved to be an independent prognostic marker with high MASP-2 levels predicting recurrence and poor survival. (PMID:15746044)
• Structural insights are presented into MASP2 autoactivation. (PMID:16040602)
• The mRNA distribution of masp1 and masp2 were found very similar to that of mbl2, while masp3 mRNA seemed ubiquitous present at quite high levels when compared to liver (PMID:16112196)
• MASP-2 expression in ESCCs was associated with late clinical stage (p = 0.009, O.R. = 3.430) and nodal metastasis (p = 0.001, O.R. = 4.520). (PMID:16395704)
• Concentrations and genotypes of MASP-2 and mannan-binding lectin in 109 cystic fibrosis patients were correlated to lung function and chronic infections (PMID:17045845)
• The data indicate a strong genetic influence for the serum levels of MBL and for MASP-2 activity with a significant genetic correlation between the two traits. (PMID:17096357)
• MASP-2 present in individuals homozygous for p.377A or p.99Q had a normal enzyme activity whereas MASP-2 in individuals homozygous for p.126L was non-functional (PMID:17252003)
• variations in MASP2 appear to be of limited importance in the pathogenesis of Crohn’s disease (PMID:17303612)
• MASP-2 is a major physiological target of C1-inhibitor. (PMID:17709141)
• We conclude that Stat3 binding is important for MASP2 promoter activity. (PMID:17971300)
• In this study, MASP-2 deficiency was associated with an increased risk of fever and neutropenia in children treated with chemotherapy for cancer. (PMID:17984804)
• Data show that interaction of calreticulin with recombinant MBL was fully inhibited by recombinant MASP-2, but not by the MASP-2 D105G variants characterized by defective MBL binding ability. (PMID:18177377)
• Our data do not seem to suggest a role for MBL2 and MASP2 polymorphisms in HCC susceptibility either for HBV-HCV infection-dependent HCC or for HCC raised as a consequence of exposure to different risk factors. (PMID:18221301)
• Results suggest that the D105G mutation in the MASP2 gene does not play a major role in the pathogenesis of rheumatic fever. (PMID:18295674)
• No association with aortic regurgitation of rheumatic etiology was detected with the variant of the MASP2 gene. (PMID:18400978)
• MASP2 alleles and genotypes did not associate with any measurment of severity or outcome of community-acquired pneumonia (PMID:18582923)
• Infants later developing necrotising enterocolitis had significantly higher MASP-2 cord blood levels compared with controls. (PMID:18596574)
• High postoperative levels of MASP-2 are associated with poor prognosis in patients curatively resected for colorectal cancer (PMID:18638656)
• Poly(ethylene glycol)s generate complement activation products in human serum through increased alternative pathway turnover and a MASP-2-dependent process (PMID:18849076)
• Naturally occurring variant forms of MASP-2 differ in mannan-binding lectin activity and enzymatic activity and may have implications for susceptibility to infections of individuals with various genotypes. (PMID:19234189)
• Serum MASP-2 concentrations correlated with gestational age and birthweight and were significantly lower in premature babies and other pre-term babies compared with term babies. (PMID:19307021)
• There is no association between MASP2 polymorphisms and susceptibility to SARS coronavirus infection. (PMID:19405982)
• SARS-CoV N interacts with MAP19 and increased the expression of MAP19 in cells. (PMID:19737459)
• The MASP2-mediated release of FPA and FPB may play a role in early immune activation. Additionally, MASP-catalysed deposition and polymerization of fibrin on the surface of micro-organisms may be protective by limiting the dissemination of infection. (PMID:20002787)
• the outcome of intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2 gene polymorphisms was studied (PMID:20042521)
• Donor and recipient gene polymorphisms in the lectin complement pathway (MBL2, FCN2, MASP2) are major determinants of the risk of clinically significant bacterial infection and mortality after orthotopic liver transplantation. (PMID:20593422)
• MASP-1 has a crucial role in the initiation steps of lectin pathway activation most probably by activating MASP-2 (PMID:20817870)
• In contrast to what has been demonstrated for serum levels of mannan-binding lectin (MBL) and MBL-associated serine protease 2, the genotypes do not predict disease course of the colorectal cancer patients (PMID:21198752)
• binding of Mannan Binding Lectin to hepatitis C virus glycoproteins was able to activate the complement system via MBL-associated serine protease 2 (PMID:21203938)
• MASP2*CD genotypes, most of them generating low MASP-2 levels, are associated with high risk of chagasic cardiomyopathy (PMID:21489885)
• MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus infection. (PMID:21843573)
• Data show that both MAp19 and MASP-2 were mainly expressed in hepatocytes. (PMID:21871896)
• Results suggest that MBL and MASP-2 play only a minor role in the inflammatory response in acute pancreatitis. (PMID:21926545)
• It is postulated that the elevation of concentration of the two components of the leptin pathway, L-ficolin and MASP-2, may compensate for the insufficient activity of the LP in mannose-binding lectin deficiency. (PMID:21974696)
• Interactions required for the cleavage of C4 by MASP-2 are likely to be facilitated by the initial binding of C4 to an exosite on the protease. (PMID:22071314)
• Data show no association of donor and recipient MBL2 and MASP2 genotype with allograft outcome, and analysis of SNPs and haplotypes in the FCN2 gene of the donor and recipient did not reveal an association with transplant outcome. (PMID:22173059)
• MASP-2 levels in the peripheral circulation are significantly reduced in myocardial infarction (MI) patients compared with those of healthy individuals or of coronary artery disease (CAD) patients without acute MI. (PMID:22178059)
• In patients with haematological malignancy undergoing chemotherapy, those with low M-ficolin levels were more likely to develop severe infections. (PMID:22236007)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	masp2	ENSDARG00000007988
mus_musculus	Masp2	ENSMUSG00000028979
rattus_norvegicus	Masp2	ENSRNOG00000011258

Paralogs (2): PRRG2 (ENSG00000126460), MASP1 (ENSG00000127241)

Protein

Protein identifiers

Mannan-binding lectin serine protease 2 — O00187 (reviewed: O00187)

Alternative names: MBL-associated serine protease 2, Mannose-binding protein-associated serine protease 2

All UniProt accessions (11): O00187, A0A8V8TP45, A0A8V8TPA2, A0A8V8TPN3, A0A8V8TPN9, A0A8V8TPT6, A0A8V8TPU1, A0A8V8TQL2, A0A8V8TQL6, A0A8V8TQY3, A0A8V8TQY5

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of a serum protease that activates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. The lectin complement system is activated following association of lectins, such as MBL2, FCN1, FCN2 or FCN3, to carbohydrates on the pathogen surface. MASP2 is cleaved and activated by MASP1 in response to lectin-binding to pathogen carbohydrates. Can activate prothrombin to thrombin. Serine protease component of the lectin complement pathway, which catalyzes cleavage and activation of C2 and C4, the next components of the complement pathway.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with MBL2 and FCN2; requires calcium ions. Interacts with SERPING1. Interacts with guianensin, an anticoagulant and anti-complement protein from Simulium guianense saliva; the interaction results in the inhibition of MASP2 enzymatic activity.

Subcellular location. Secreted Secreted. Cell surface.

Tissue specificity. Plasma.

Post-translational modifications. Activated by cleavage after Arg-444 by MASP1. The uncleaved zymogen is inactive towards synthetic substrates, but has sufficient activity to effect autocatalytic cleavage. The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

Disease relevance. MASP2 deficiency (MASPD) [MIM:613791] A disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The protease activity is specifically inhibited by SGMI-2 small protein inhibitor. (Microbial infection) Serine protease activity is inhibited by E.Coli ecotin (eco).

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00187-1	1	yes
O00187-2	2, MAp19, Small MBL-associated protein, sMAP

RefSeq proteins (2): NP_006601, NP_631947 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR000742	EGF	Domain
IPR000859	CUB_dom	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR024175	Pept_S1A_C1r/C1S/mannan-bd	Family
IPR033116	TRYPSIN_SER	Active_site
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR043504
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF00084, PF00089, PF00431, PF07645

Enzyme classification (BRENDA):

• EC 3.4.21.104 — mannan-binding lectin-associated serine protease-2 (BRENDA: 5 organisms, 101 substrates, 31 inhibitors, 26 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
COMPLEMENT COMPONENT C4	0.0001–74	8
COMPLEMENT COMPONENT C2	0.0052–6.5	5
C1-INHIBITOR P4-P1 FRAGMENT	0.123	1
C1-INHIBITOR P4-P4’ FRAGMENT	0.123	1
COMPLEMENT COMPONENT C2 P4-P1 FRAGMENT	0.015	1
COMPLEMENT COMPONENT C2 P4-P4’ FRAGMENT	0.173	1
COMPLEMENT COMPONENT C4 P4-P1 FRAGMENT	0.0155	1
COMPLEMENT COMPONENT C4 P4-P4’ FRAGMENT	0.271	1
N-ACETYLGLYCINE-L-LYSINE METHYL ESTER	6.7	1
N-CARBOXYBENZOYLGLYCINE-L-ARGININE THIOBENZYL ES	40	1
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER	4.4	1
P-TOSYL-L-ARGININE METHYL ESTER	2.8	1
ABZ-GLQRALEI-LYS(DNP)-NH2	—	0
ABZ-SLGRKIQI-LYS(DNP)-NH2	—	0

UniProt features (120 total): strand 35, binding site 15, disulfide bond 12, sequence variant 11, sequence conflict 10, mutagenesis site 9, turn 6, domain 6, helix 5, chain 3, active site 3, splice variant 2, signal peptide 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
3TVJ	X-RAY DIFFRACTION	1.28
9D40	X-RAY DIFFRACTION	1.76
9D17	X-RAY DIFFRACTION	1.97
9D3Y	X-RAY DIFFRACTION	2.08
1ZJK	X-RAY DIFFRACTION	2.18
1Q3X	X-RAY DIFFRACTION	2.23
9D4D	X-RAY DIFFRACTION	2.36
7PQN	X-RAY DIFFRACTION	2.4
1SZB	X-RAY DIFFRACTION	2.5
5JPM	X-RAY DIFFRACTION	3.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00187-F1	89.73	0.74

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): 483 (charge relay system); 532 (charge relay system); 633 (charge relay system); 444–445 (cleavage; by masp1)

Ligand- & substrate-binding residues (15): 67; 75; 120; 122; 123; 138; 139; 141; 158; 159; 162; 234 …

Post-translational modifications (1): 158

Disulfide bonds (12): 142–156, 152–165, 167–180, 300–348, 328–361, 366–412, 396–430, 434–552, 434, 552, 598–618, 629–660

Mutagenesis-validated functional residues (9):

Position	Phenotype
74	strongly decreases affinity for mbl2. decreases affinity for fcn2.
121	strongly decreases affinity for mbl2, but not for fcn2.
124	decreases affinity for mbl2. slight decrease in affinity for fcn2.
333	reduced ability to cleave complement c4.
340	reduced ability to cleave complement c4.
365	reduced ability to cleave complement c4.
368	reduced ability to cleave complement c4.
444	abolishes cleavage.
633	abolished serine protease activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-166662	Lectin pathway of complement activation
R-HSA-166663	Initial triggering of complement
R-HSA-2855086	Ficolins bind to repetitive carbohydrate structures on the target cell surface
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 188 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GNF2_GSTM1, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GNF2_HPN, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, MORF_RAD51L3, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_ACTIVATION

GO Biological Process (7): complement activation, lectin pathway (GO:0001867), proteolysis (GO:0006508), complement activation, classical pathway (GO:0006958), immune system process (GO:0002376), complement activation (GO:0006956), humoral immune response (GO:0006959), innate immune response (GO:0045087)

GO Molecular Function (10): complement component C4b binding (GO:0001855), serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), peptidase activity (GO:0008233), identical protein binding (GO:0042802), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Creation of C4 and C2 activators	1
Complement cascade	1
Lectin pathway of complement activation	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	2
immune response	2
protein binding	2
innate immune response	1
protein metabolic process	1
humoral immune response mediated by circulating immunoglobulin	1
biological_process	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
defense response to symbiont	1
opsonin binding	1
complement binding	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
calcium ion binding	1
binding	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MASP2	MBL2	P11226	994
MASP2	SERPING1	P05155	990
MASP2	FCN2	Q15485	989
MASP2	FCN3	O75636	965
MASP2	FCN1	O00602	965
MASP2	COLEC11	Q9BWP8	892
MASP2	COLEC10	Q9Y6Z7	880
MASP2	C4A	P01028	853
MASP2	C4A	P01028	845
MASP2	F8W876	F8W876	806
MASP2	KIR3DL1	P43629	772
MASP2	C3	P01024	721
MASP2	EGF	P01133	719
MASP2	CFP	P27918	673
MASP2	CLEC12A	Q5QGZ9	662

IntAct

43 interactions, top by confidence:

A	B	Type	Score
	MASP2	psi-mi:“MI:0407”(direct interaction)	0.750
	MASP2	psi-mi:“MI:0915”(physical association)	0.750
	MASP2	psi-mi:“MI:0914”(association)	0.750
MASP2	C4A	psi-mi:“MI:0407”(direct interaction)	0.680
C4A	MASP2	psi-mi:“MI:0570”(protein cleavage)	0.680
SERPING1	MASP2	psi-mi:“MI:0194”(cleavage reaction)	0.680
SERPING1	MASP2	psi-mi:“MI:0915”(physical association)	0.680
SERPING1	MASP2	psi-mi:“MI:0407”(direct interaction)	0.680
MBL2	MASP2	psi-mi:“MI:0407”(direct interaction)	0.610
MASP2	MBL2	psi-mi:“MI:0915”(physical association)	0.610
COLEC11	MASP2	psi-mi:“MI:0915”(physical association)	0.520
MASP2	COLEC11	psi-mi:“MI:0915”(physical association)	0.520
MASP2		psi-mi:“MI:0570”(protein cleavage)	0.440
MASP2		psi-mi:“MI:0407”(direct interaction)	0.440
	MASP2	psi-mi:“MI:0194”(cleavage reaction)	0.440

BioGRID (24): MASP2 (Negative Genetic), MASP2 (Negative Genetic), MASP2 (Negative Genetic), MASP2 (Negative Genetic), MASP2 (Positive Genetic), MASP2 (Positive Genetic), SLC16A8 (Positive Genetic), RPS6KA4 (Positive Genetic), MASP2 (Affinity Capture-Western), MASP2 (Affinity Capture-Western), MASP2 (Affinity Capture-MS), MASP2 (Reconstituted Complex), FCN2 (Reconstituted Complex), MASP2 (Affinity Capture-MS), MASP2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Y0, A1KZ92, A2AJ76, B0S5N4, D3YXG0, D3ZPX4, F1MMS9, O00187, O55005, O60500, O75093, O88279, O88280, P11627, P17852, P26006, P32004, P51805, P57110, P59511, P70208, P85171, Q05695, Q0PMG2, Q13219, Q3UH53, Q4KMG0, Q62470, Q62918, Q7Z5N4, Q80TR4, Q8AV58, Q8AXZ4, Q8CIY2, Q8HZK2, Q8HZK3, Q8NDA2, Q8R4K8, Q8TE57, Q91WP0

Diamond homologs: A6MFK7, A6MFK8, B5G6G5, O00187, O15393, O18783, O19045, O88947, O97399, P00734, P00735, P00740, P00741, P00742, P00743, P00745, P00747, P00760, P03952, P04070, P06867, P08709, P12545, P14272, P16291, P16292, P16293, P16294, P16295, P16296, P17538, P19221, P19540, P22457, P22891, P25155, P26262, P28175, P29786, P29787

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
MBL2	“up-regulates activity”	MASP2	binding
MASP2	“up-regulates activity”	C2	cleavage
MASP2	“form complex”	“Ficolin lectin-protease complex”	binding
FCN3	“up-regulates activity”	MASP2	binding
FCN2	“up-regulates activity”	MASP2	binding
MASP2	“up-regulates activity”	C4B	cleavage
MASP2	“up-regulates activity”	C4A	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	135
Likely benign	20
Benign	14

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1678023	NM_006610.4(MASP2):c.1515_1516dup (p.Ser506fs)	Likely pathogenic
1678096	NM_006610.4(MASP2):c.1126C>T (p.Arg376Ter)	Likely pathogenic
4279079	NM_006610.4(MASP2):c.716C>G (p.Thr239Ser)	Likely pathogenic

SpliceAI

2321 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11030743:CATA:C	donor_loss	1.0000
1:11030744:ATAC:A	donor_loss	1.0000
1:11030745:TA:T	donor_loss	1.0000
1:11030746:A:AC	donor_gain	1.0000
1:11030746:ACC:A	donor_loss	1.0000
1:11030747:C:CC	donor_gain	1.0000
1:11030747:C:T	donor_loss	1.0000
1:11030747:CCAT:C	donor_gain	1.0000
1:11030760:T:A	donor_gain	1.0000
1:11030878:AACAA:A	acceptor_gain	1.0000
1:11030879:ACAA:A	acceptor_gain	1.0000
1:11030880:CAA:C	acceptor_gain	1.0000
1:11030880:CAAC:C	acceptor_gain	1.0000
1:11030882:ACTAA:A	acceptor_loss	1.0000
1:11030883:C:CC	acceptor_gain	1.0000
1:11042870:CTCA:C	donor_loss	1.0000
1:11042871:TCA:T	donor_loss	1.0000
1:11042873:ACCT:A	donor_loss	1.0000
1:11042874:C:CT	donor_loss	1.0000
1:11045402:CCTCA:C	donor_loss	1.0000
1:11045403:CTCAC:C	donor_loss	1.0000
1:11045404:TCA:T	donor_loss	1.0000
1:11045407:C:T	donor_loss	1.0000
1:11045441:AG:A	donor_gain	1.0000
1:11045537:TGT:T	acceptor_gain	1.0000
1:11045540:C:CG	acceptor_loss	1.0000
1:11046554:AC:A	donor_gain	1.0000
1:11046555:CC:C	donor_gain	1.0000
1:11046879:T:TA	donor_gain	1.0000
1:11046905:A:AC	donor_gain	1.0000

AlphaMissense

4485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11042899:A:G	W289R	0.995
1:11042899:A:T	W289R	0.995
1:11027227:C:A	W573C	0.994
1:11027227:C:G	W573C	0.994
1:11027342:A:G	L535P	0.994
1:11043486:G:C	S198R	0.994
1:11043486:G:T	S198R	0.994
1:11043488:T:G	S198R	0.994
1:11027572:C:A	W458C	0.993
1:11027572:C:G	W458C	0.993
1:11027346:C:G	A534P	0.992
1:11027351:T:A	D532V	0.992
1:11027574:A:G	W458R	0.992
1:11027574:A:T	W458R	0.992
1:11027093:C:G	C618S	0.991
1:11027094:A:T	C618S	0.991
1:11027229:A:G	W573R	0.991
1:11027229:A:T	W573R	0.991
1:11042897:C:A	W289C	0.991
1:11042897:C:G	W289C	0.991
1:11027351:T:G	D532A	0.990
1:11046895:A:T	V77D	0.990
1:11026912:C:A	W678C	0.989
1:11026912:C:G	W678C	0.989
1:11027510:A:G	L479P	0.989
1:11030219:C:A	W418C	0.989
1:11030219:C:G	W418C	0.989
1:11027345:G:T	A534E	0.988
1:11046578:G:C	F130L	0.988
1:11046578:G:T	F130L	0.988

dbSNP variants (sampled 300 via entrez): RS1000159796 (1:11035229 C>T), RS1000192621 (1:11031371 A>T), RS1000357083 (1:11030029 G>A), RS1000440594 (1:11028865 C>G,T), RS1000582933 (1:11035341 T>A,C), RS1000611906 (1:11046617 G>C,T), RS1000615044 (1:11035463 G>A,T), RS1001211713 (1:11029964 A>G), RS1001507648 (1:11040487 G>T), RS1001578259 (1:11039992 A>C), RS1001600944 (1:11040953 G>A), RS1001630495 (1:11040362 T>G), RS1001671899 (1:11034967 G>A,T), RS1001717091 (1:11035138 A>C,G), RS1001766989 (1:11029391 T>C)

Disease associations

OMIM: gene MIM:605102 | disease phenotypes: MIM:613791, MIM:612069

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency due to MASP-2 deficiency	Strong	Autosomal recessive

Mondo (2): immunodeficiency due to MASP-2 deficiency (MONDO:0013423), amyotrophic lateral sclerosis type 10 (MONDO:0012790)

Orphanet (3): Immunodeficiency due to MASP-2 deficiency (Orphanet:331187), Frontotemporal dementia with motor neuron disease (Orphanet:275872), Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002725	Systemic lupus erythematosus
HP:0004431	Reduced circulating complement concentration
HP:0006532	Recurrent pneumonia
HP:0100279	Ulcerative colitis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003475_1	Beard thickness	4.000000e-07
GCST006661_190	Male-pattern baldness	1.000000e-08
GCST008129_67	Body mass index	1.000000e-08
GCST90000025_899	Appendicular lean mass	6.000000e-29
GCST90002382_56	Eosinophil percentage of white cells	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567429	Amyotrophic Lateral Sclerosis 10 (supp.)
C565360	MASP2 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295646 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
narsoplimab	Binding	10.05	pKd

Binding affinities (BindingDB)

5 measured of 15 human assays (15 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxopropan-2-yl]-4-phenylpiperidine-2-carboxamide	KI	1500 nM	US-12351648: Methods of inhibiting MASP-2 for the treatment and/or prevention of coronavirus-induced acute respiratory distress syndrome
[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-1-oxopropan-2-yl] (2R)-2-amino-4-phenylbutanoate	KI	1500 nM	US-12351648: Methods of inhibiting MASP-2 for the treatment and/or prevention of coronavirus-induced acute respiratory distress syndrome
(2R)-2-amino-N-[(2S)-1-[[5-chloro-2-(tetrazol-1-yl)phenyl]methylamino]-1-oxopropan-2-yl]-4-phenylbutanamide	KI	1500 nM	US-12351648: Methods of inhibiting MASP-2 for the treatment and/or prevention of coronavirus-induced acute respiratory distress syndrome
(2R)-2-amino-N-[(2S)-1-[(3-chlorophenyl)methylamino]-1-oxopropan-2-yl]-4-phenylbutanamide	KI	6250 nM	US-12351648: Methods of inhibiting MASP-2 for the treatment and/or prevention of coronavirus-induced acute respiratory distress syndrome
ethyl 2-[2-[[[(2S)-2-[[(2R)-2-amino-4-phenylbutanoyl]amino]propanoyl]amino]methyl]-4-chlorophenoxy]acetate	KI	6250 nM	US-12351648: Methods of inhibiting MASP-2 for the treatment and/or prevention of coronavirus-induced acute respiratory distress syndrome

ChEMBL bioactivities

163 potent at pChembl≥5 of 208 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.66	IC50	2.2	nM	CHEMBL6152811
8.54	IC50	2.9	nM	CHEMBL6166990
8.40	IC50	4	nM	CHEMBL6173670
8.33	IC50	4.7	nM	CHEMBL6147067
8.33	IC50	4.7	nM	CHEMBL6172668
8.26	IC50	5.5	nM	CHEMBL6161113
8.22	Ki	6	nM	CHEMBL4242955
8.16	IC50	6.9	nM	CHEMBL6147698
8.13	IC50	7.4	nM	CHEMBL6142574
8.12	IC50	7.5	nM	CHEMBL6169123
8.10	IC50	7.9	nM	CHEMBL6169003
8.07	IC50	8.5	nM	CHEMBL6145812
8.05	IC50	9	nM	CHEMBL6168625
8.02	IC50	9.5	nM	CHEMBL6143502
7.94	IC50	11.4	nM	CHEMBL6152856
7.90	IC50	12.7	nM	CHEMBL6165656
7.90	IC50	12.5	nM	CHEMBL6175367
7.80	IC50	16	nM	CHEMBL6152247
7.76	IC50	17.5	nM	CHEMBL6169206
7.52	IC50	30	nM	CHEMBL6165071
7.34	IC50	45.4	nM	CHEMBL6141888
7.33	IC50	46.3	nM	CHEMBL6164878
7.18	IC50	66	nM	CHEMBL4242955
7.17	IC50	68.3	nM	CHEMBL6148853
7.02	IC50	95.2	nM	CHEMBL6169169
6.93	IC50	117	nM	CHEMBL6145695
6.91	IC50	124	nM	CHEMBL6170915
6.90	IC50	125	nM	CHEMBL6176116
6.81	IC50	155	nM	CHEMBL6151851
6.75	Ki	180	nM	CHEMBL4246684
6.69	IC50	206	nM	CHEMBL6170662
6.64	IC50	230	nM	CHEMBL4240381
6.59	IC50	257	nM	CHEMBL6167664
6.49	IC50	323	nM	CHEMBL6148213
6.36	Ki	440	nM	CHEMBL4242095
6.01	IC50	976	nM	CHEMBL6134267
5.99	Ki	1030	nM	CHEMBL4240381
5.82	Ki	1500	nM	CHEMBL5804052
5.82	Ki	1500	nM	CHEMBL5863724
5.82	Ki	1500	nM	CHEMBL5888856
5.82	Ki	1500	nM	CHEMBL5882970
5.82	Ki	1500	nM	CHEMBL5751330
5.82	Ki	1500	nM	CHEMBL5937862
5.82	Ki	1500	nM	CHEMBL5870074
5.82	Ki	1500	nM	CHEMBL6054572
5.82	Ki	1500	nM	CHEMBL5902541
5.82	Ki	1500	nM	CHEMBL5963602
5.82	Ki	1500	nM	CHEMBL5768713
5.82	Ki	1500	nM	CHEMBL5864485
5.82	Ki	1500	nM	CHEMBL5801221

PubChem BioAssay actives

7 with measured affinity, of 9 total; 4 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
(4S)-4-amino-5-[[(2S)-1-[[(2S,3R)-1-[[(2R)-1-[[(2S)-1-[(2S)-2-[[2-[[(2S,3R)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2R)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2R)-1-[[(2S)-1-[[(2R)-1-[[2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S,3R)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-4-amino-1-[[(1S)-4-amino-1-carboxy-4-oxobutyl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1393230: Inhibition of recombinant CP1-CCP2-SP fragment of MASP-2 (unknown origin)	ki	0.0060	uM
(2S)-2-[[(2S)-1-[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-sulfanylpropanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]butanedioic acid	1393226: Inhibition of MASP-2 (unknown origin) using Z-L-LysSBzl hydrochloride as substrate preincubated for 1 hr followed by substrate addition	ki	0.1800	uM
(2S)-2-[[(2S)-1-[(2S,3S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[(2-aminoacetyl)amino]-3-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]butanedioic acid	1393227: Inhibition of MASP-2-mediated C4 deposition in human serum after 1 hr by ELISA	ic50	0.2300	uM
[3-[[[3-[2-amino-4-(diaminomethylideneamino)-6-methylphenyl]phenyl]-(5-carbamimidoyl-2-methylsulfanylthiophen-3-yl)-oxo-lambda6-sulfanylidene]amino]sulfonylphenyl]urea	1393224: Inhibition of human His-tagged MASP-2 (Cys300 to Phe686 residues) expressed in baculovirus infected insect cells using Z-Gly-Arg-S-Bzl as substrate preincubated with substrate for 10 mins followed by enzyme addition and measured for 15 mins	ki	0.4400	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
jinfukang	decreases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Lead	affects methylation	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases expression	1
Gold Compounds	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
S-Nitrosoglutathione	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4229694	Binding	Inhibition of human His-tagged MASP-2 (Cys300 to Phe686 residues) expressed in baculovirus infected insect cells using Z-Gly-Arg-S-Bzl as substrate preincubated with substrate for 10 mins followed by enzyme addition and measured for 15 mins	Chemical Approaches to Modulating Complement-Mediated Diseases. — J Med Chem

Clinical trials (associated diseases)

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