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): 225 total — 3 likely-pathogenic
• GTEx eGene: eQTL in 17 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 5
• Drug target: yes — 1 curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.16 (unconstrained)
• 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: 46 — 24 protein_coding, 18 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000400897

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

ENST00000400897, ENST00000400898, ENST00000478645, ENST00000480221, ENST00000699927, ENST00000699958, ENST00000700088, ENST00000700089, ENST00000700090, ENST00000700091, ENST00000700092, ENST00000700093, ENST00000700094, ENST00000700095, ENST00000700096, ENST00000700097, ENST00000700098, ENST00000860325, ENST00000860326, ENST00000860327, ENST00000860328, ENST00000860329, ENST00000992437, ENST00000992439, ENST00000992440, ENST00000992442, ENST00000992445, ENST00000992446, ENST00000992447, ENST00000992448, ENST00000992449, ENST00000992450, ENST00000992452, ENST00000992453, ENST00000992454, ENST00000992455, ENST00001110597, ENST00001110598, ENST00001110599, ENST00001110600, ENST00001110601, ENST00001110602, ENST00001110603, ENST00001110604, ENST00001110605, ENST00001144163

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.

Highest expression (Bgee): lobe of liver, liver, cerebellar hemisphere, cerebellar cortex, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MASP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	sqtl	2.2e-24	+2.71	1:11046609:T:C
Nerve Tibial	eqtl	4.5e-14	-0.19	1:11013450:TCA:T
Liver	eqtl	8.4e-10	+0.46	1:11044788:T:C
Skin Sun Exposed Lower leg	eqtl	6.9e-07	-0.14	1:11030859:C:A
Adipose Subcutaneous	eqtl	5.0e-06	-0.14	1:11012828:C:T
Artery Tibial	eqtl	8.6e-04	-0.13	1:11008929:A:G
Esophagus Muscularis	eqtl	2.2e-03	+0.52	1:11716927:A:G
Cells EBV-transformed lymphocytes	eqtl	2.4e-03	-0.56	1:11951811:C:T
Skin Not Sun Exposed Suprapubic	eqtl	3.4e-03	-0.10	1:11036365:G:A
Thyroid	eqtl	6.3e-03	-0.10	1:11034608:G:A
Artery Aorta	eqtl	1.1e-02	-0.14	1:11030859:C:A
Colon Transverse	eqtl	1.1e-02	+0.30	1:11025595:GAA:G
Pituitary	eqtl	1.3e-02	-1.00	1:11908352:G:C
Brain Frontal Cortex BA9	eqtl	2.1e-02	-0.37	1:10782712:G:A
Cells Cultured fibroblasts	eqtl	2.5e-02	-0.08	1:10311796:A:G
Artery Coronary	eqtl	2.6e-02	+0.47	1:11559582:C:T
Muscle Skeletal	eqtl	2.8e-02	+0.18	1:11304863:T:C
Brain Amygdala	eqtl	3.4e-02	-0.80	1:10115552:T:A

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

showing 100 of 292 tissues 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
stromal cell of endometrium	CL:0002255	70.18	gold quality
left ovary	UBERON:0002119	70.07	gold quality
body of pancreas	UBERON:0001150	69.98	gold quality
right uterine tube	UBERON:0001302	69.77	gold quality
body of stomach	UBERON:0001161	69.76	gold quality
right coronary artery	UBERON:0001625	69.50	gold quality
medial globus pallidus	UBERON:0002477	69.39	silver quality
hindlimb stylopod muscle	UBERON:0004252	69.28	gold quality
muscle organ	UBERON:0001630	69.19	gold quality
aorta	UBERON:0000947	69.12	gold quality
rectum	UBERON:0001052	68.74	gold quality
endocervix	UBERON:0000458	68.64	gold quality
minor salivary gland	UBERON:0001830	68.19	gold quality
zone of skin	UBERON:0000014	68.17	gold quality
small intestine	UBERON:0002108	67.93	gold quality
descending thoracic aorta	UBERON:0002345	67.67	gold quality
thoracic aorta	UBERON:0001515	67.32	gold quality
left coronary artery	UBERON:0001626	67.28	gold quality
ascending aorta	UBERON:0001496	67.08	gold quality
smooth muscle tissue	UBERON:0001135	67.07	gold quality
heart right ventricle	UBERON:0002080	66.99	gold quality
subcutaneous adipose tissue	UBERON:0002190	66.93	gold quality
right lobe of thyroid gland	UBERON:0001119	66.88	gold quality
pancreas	UBERON:0001264	66.77	gold quality
ectocervix	UBERON:0012249	66.64	gold quality
stomach	UBERON:0000945	66.48	gold quality
apex of heart	UBERON:0002098	66.41	gold quality
cortical plate	UBERON:0005343	66.37	gold quality
saliva-secreting gland	UBERON:0001044	66.29	gold quality
coronary artery	UBERON:0001621	66.28	gold quality
ovary	UBERON:0000992	66.25	gold quality
esophagus	UBERON:0001043	66.13	gold quality
mouth mucosa	UBERON:0003729	65.92	gold quality
nasal cavity epithelium	UBERON:0005384	65.91	gold quality
colon	UBERON:0001155	65.90	gold quality
colonic epithelium	UBERON:0000397	65.86	silver quality
intestine	UBERON:0000160	65.80	gold quality
spleen	UBERON:0002106	65.79	gold quality
heart left ventricle	UBERON:0002084	65.57	gold quality
right adrenal gland cortex	UBERON:0035827	65.55	gold quality
right frontal lobe	UBERON:0002810	65.39	gold quality
cardiac ventricle	UBERON:0002082	65.38	gold quality
upper lobe of left lung	UBERON:0008952	65.27	gold quality
globus pallidus	UBERON:0001875	65.25	silver quality
right adrenal gland	UBERON:0001233	65.24	gold quality
left adrenal gland	UBERON:0001234	65.19	gold quality
sigmoid colon	UBERON:0001159	65.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.15	gold quality
large intestine	UBERON:0000059	65.09	gold quality
tendon	UBERON:0000043	65.05	gold quality
adenohypophysis	UBERON:0002196	65.04	gold quality
left lobe of thyroid gland	UBERON:0001120	64.95	gold quality
granulocyte	CL:0000094	64.94	gold quality
metanephros cortex	UBERON:0010533	64.69	gold quality
left adrenal gland cortex	UBERON:0035825	64.56	gold quality
pituitary gland	UBERON:0000007	64.55	gold quality
islet of Langerhans	UBERON:0000006	64.52	gold quality
ganglionic eminence	UBERON:0004023	64.40	gold quality
type B pancreatic cell	CL:0000169	64.33	gold quality
heart	UBERON:0000948	64.33	gold quality
right atrium auricular region	UBERON:0006631	64.30	gold quality
thyroid gland	UBERON:0002046	64.20	gold quality
primary visual cortex	UBERON:0002436	64.17	gold quality
calcaneal tendon	UBERON:0003701	64.02	gold quality
lymph node	UBERON:0000029	64.01	gold quality
fundus of stomach	UBERON:0001160	63.90	gold quality
tongue squamous epithelium	UBERON:0006919	63.87	gold quality
skeletal muscle tissue	UBERON:0001134	63.83	gold quality
upper lobe of lung	UBERON:0008948	63.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.72	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

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 65 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	176.7	not detected
Postcentral gyrus	tissue	5.8
Bone marrow	tissue	4.9	not detected
Nucleus accumbens	tissue	4.6
Retina	tissue	4.2
Choroid plexus	tissue	4.0
Hippocampus	tissue	3.7	not detected
Skin 1	tissue	3.6	not detected
Skeletal muscle	tissue	3.3	not detected
Locus coeruleus	tissue	3.3
Pituitary gland	tissue	2.2
Lymph node	tissue	1.9	not detected
Salivary gland	tissue	1.8	not detected
Spinal cord	tissue	1.8
Olfactory bulb	tissue	1.7
Cerebral cortex	tissue	1.6	not detected
Spleen	tissue	1.6	not detected
Temporal cortex	tissue	1.6
Vagina	tissue	1.5	not detected
Midbrain	tissue	1.5
Cerebellum	tissue	1.5	not detected
Small intestine	tissue	1.5	not detected
Hippocampal formation	tissue	1.5
Entorhinal cortex	tissue	1.5
Ventral forebrain	tissue	1.5
Occipital cortex	tissue	1.5
Insular cortex	tissue	1.5
Prefrontal cortex	tissue	1.4
Motor cortex	tissue	1.4
Amygdala	tissue	1.4
Duodenum	tissue	1.4	not detected
Retrosplenial and cingulate cortex	tissue	1.4
Basal ganglia	tissue	1.3	not detected
Medulla oblongata	tissue	1.3
Thalamus	tissue	1.3
Superior colliculi	tissue	1.3
Substantia nigra	tissue	1.3
Somatosensory cortex	tissue	1.3
Appendix	tissue	1.3	not detected
Putamen	tissue	1.2
Retrosplenial cortex	tissue	1.2
Endometrium 1	tissue	1.1	not detected
Periaqueductal gray	tissue	1.1
Septum	tissue	1.1
Stomach 1	tissue	1.0	not detected
Pons	tissue	1.0
Pancreas	tissue	1.0	not detected
Hypothalamus	tissue	1.0
Corpus callosum	tissue	1.0
Thyroid gland	tissue	0.9	not detected
Lung	tissue	0.9	not detected
Gallbladder	tissue	0.9	not detected
Heart muscle	tissue	0.8	not detected
Adrenal gland	tissue	0.7	not detected
Adipose tissue	tissue	0.6	not detected
Esophagus	tissue	0.6	not detected
Ovary	tissue	0.5	not detected
Prostate	tissue	0.5	not detected
Placenta	tissue	0.4	not detected
Testis	tissue	0.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (14.5), Cerebellar cortex (14.0), Vermis (13.6), Postcentral gyrus, middle (6.7), Area striata (6.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

Targeting MASP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 33 miRNAs:

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

gnomAD constraint: pLI 4e-13, LOEUF 1.16, missense Z -0.204 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000400897 — one region, missense o/e 1.03. 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1330832) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal complement pathway	1
decreased myocardial infarct size	1
decreased susceptibility to injury	1
impaired lectin complement pathway	1

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
Pongo pygmaeus	Q8SQ75	99.6%	Diamond
Pan troglodytes	Q8SQ74	99.5%	Diamond
Gorilla gorilla gorilla	Q863A0	99.3%	Diamond
Pongo abelii	Q5RA73	99.2%	Diamond
Macaca fascicularis	Q4R577	96.3%	Diamond
Pseudonaja textilis	Q1L658	93.4%	Diamond
Cryptophis nigrescens	B5G6G5	89.2%	Diamond
Gallus gallus	Q9DER7	88.6%	Diamond
Xenopus laevis	Q8JI28	87.1%	Diamond
Pseudechis porphyriacus	Q58L93	86.1%	Diamond
Demansia vestigiata	A6MFK7	85.8%	Diamond
Mesocricetus auratus	O35086	85.6%	Diamond
Canis lupus familiaris	P19006	83.1%	Diamond
Bos taurus	Q0VCX1	82.7%	Diamond
Sus scrofa	Q69DK8	82.7%	Diamond
Drosophila melanogaster	P25723	57.5%	Diamond
Caenorhabditis elegans	Q20911	54.8%	Diamond
Tachypleus tridentatus	Q27081	41.5%	Diamond
Anopheles gambiae	Q7PEV7	41.2%	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
MTOR-AS1	ncRNA	100873935
TARDBP	protein-coding	23435
MTOR	protein-coding	2475
EXOSC10	protein-coding	5394
SRM	protein-coding	6723
CIROZ	protein-coding	148345
EXOSC10-AS1	ncRNA	105376736

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 (127 total): strand 36, binding site 15, helix 13, disulfide bond 12, sequence variant 11, sequence conflict 10, mutagenesis site 9, domain 6, turn 4, chain 3, active site 3, splice variant 2, signal peptide 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
3TVJ	Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed …	X-RAY DIFFRACTION	1.28
9D40	Crystal structure of the catalytic region of human MASP-2 with specific inhibitor Analog …	X-RAY DIFFRACTION	1.76
9D17	Crystal structure of the catalytic region of human MASP-2 with specific inhibitor …	X-RAY DIFFRACTION	1.97
9D3Y	Crystal structure of the catalytic region of human MASP-2 with specific inhibitor …	X-RAY DIFFRACTION	2.08
1ZJK	Crystal structure of the zymogen catalytic region of human MASP-2	X-RAY DIFFRACTION	2.18
1Q3X	Crystal structure of the catalytic region of human MASP-2	X-RAY DIFFRACTION	2.23
9D4D	Crystal structure of the catalytic region of human MASP-2 with specific inhibitor …	X-RAY DIFFRACTION	2.36
7PQN	Catalytic fragment of MASP-2 in complex with ecotin	X-RAY DIFFRACTION	2.4
1SZB	Crystal structure of the human MBL-associated protein 19 (MAp19)	X-RAY DIFFRACTION	2.5
5JPM	Structure of the complex of human complement C4 with MASP-2 rebuilt using iMDFF	X-RAY DIFFRACTION	3.75

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted secreted proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH uncertain · IF supported

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)

Position	Role
483	charge relay system
532	charge relay system
633	charge relay system
444–445	cleavage; by masp1

Ligand- & substrate-binding residues (15)

Position	Role
67	Ca(2+)
75	Ca(2+)
120	Ca(2+)
122	Ca(2+)
123	Ca(2+)
138	Ca(2+)
139	Ca(2+)
141	Ca(2+)
158	Ca(2+)
159	Ca(2+)
162	Ca(2+)
234	Ca(2+)
244	Ca(2+)
281	Ca(2+)
283	Ca(2+)

Post-translational modifications (1)

Type	Positions
(3r)-3-hydroxyasparagine	158

Disulfide bonds (12)

Type	Positions
Disulfide bond	142–156, 152–165, 167–180, 300–348, 328–361, 366–412, 396–430, 434–552, 598–618, 629–660
Interchain (with c-552)	434
Interchain (with c-434)	552

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

4 pathways:

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

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 (6): complement activation, lectin pathway (GO:0001867), proteolysis (GO:0006508), complement activation, classical pathway (GO:0006958), immune system process (GO:0002376), complement activation (GO:0006956), 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 (4): extracellular region (GO:0005576), Golgi apparatus (GO:0005794), cell surface (GO:0009986), extracellular exosome (GO:0070062)

Reactome top-level categories

4 top-level categories:

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

30 GO namespaces:

Category	Terms
complement activation	2
protein binding	2
cellular anatomical structure	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
immune response	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
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
complement activation, lectin pathway	BP	direct assay
Golgi apparatus	CC	direct assay
extracellular exosome	CC	high-throughput assay
calcium-dependent protein binding	MF	physical interaction
complement component C4b binding	MF	direct assay
identical protein binding	MF	physical interaction
peptidase activity	MF	direct assay
serine-type endopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,008 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MASP2	SERPING1	P05155	882
MASP2	MBL2	P11226	856
MASP2	C4A	P01028	850
MASP2	C4A	P01028	839
MASP2	CCDC137	Q6PK04	825
MASP2	FCN2	Q15485	776
MASP2	FCN3	O75636	764
MASP2	FCN1	O00602	761
MASP2	COLEC11	Q9BWP8	720
MASP2	C3	P01024	718
MASP2	CFP	P27918	676
MASP2	C5AR1	P21730	635
MASP2	F8W876	F8W876	621
MASP2	COLEC10	Q9Y6Z7	586
MASP2	MISP	Q8IVT2	582

IntAct

Human interaction partners of MASP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
C4A	direct interaction	0.680	7
SERPING1	cleavage reaction	0.680	3
MBL2	direct interaction	0.610	6
COLEC11	physical association	0.520	3
ALB	direct interaction	0.440	2
TFPI	cleavage reaction	0.440	1
FCN1	physical association	0.400	1
N	physical association	0.400	1
MASP1	association	0.350	1

BioGRID (25 interactions; top human partners by supporting records): MBL2 (Affinity Capture-Western; 2 records), ADRBK1 (Negative Genetic), AOC3 (Negative Genetic), BIRC5 (Negative Genetic), C4A (Biochemical Activity), CASK (Positive Genetic), CHD1 (Positive Genetic), EP300 (Affinity Capture-MS), FCN2 (Reconstituted Complex), FZR1 (Affinity Capture-MS), LCK (Negative Genetic), MASP1 (Affinity Capture-Western), POLI (Reconstituted Complex), RNF8 (Proximity Label-MS), RPS6KA4 (Positive Genetic)

SIGNOR signaling

showing 7 of 12 signaling 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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
MBL-II complex	3	MASP1, MASP2, MBL2

Disease & clinical

Genetic variants

Variant evidence for MASP2: 225 ClinVar records (3 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	137
Likely benign	37
Benign	9

Top pathogenic / likely-pathogenic (3)

Showing all 3 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
1678096	NM_006610.4(MASP2):c.1126C>T (p.Arg376Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1678023	NM_006610.4(MASP2):c.1515_1516dup (p.Ser506fs)	Likely pathogenic	criteria provided, single submitter	1
4279079	NM_006610.4(MASP2):c.716C>G (p.Thr239Ser)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore MASP2’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; 36 predictions of 987):

Position(s)	Effect	Δscore	Sites
1:11030746–11030747	donor_loss	1.0000	5
1:11030760	donor_gain	1.0000
1:11030883–11030884	acceptor_loss	1.0000	6
1:11042873–11042874	donor_loss	1.0000	5
1:11045406–11045407	donor_loss	1.0000	5
1:11030753	donor_gain	0.9900
1:11030896	acceptor_gain	0.9900
1:11045540–11045541	acceptor_loss	0.9900	5
1:11046554–11046555	donor_loss	0.9900	6
1:11046875	donor_gain	0.9900

AlphaMissense

1,088 missense substitutions predicted likely pathogenic (of 4,485 scored), across 288 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
M616	9	0.789	0.929
D532	8	0.973	0.992
D75	8	0.941	0.981
F130	8	0.931	0.988
D632	8	0.925	0.972
F61	8	0.910	0.983
D627	8	0.902	0.969
F231	8	0.893	0.974
F117	8	0.890	0.977
F278	8	0.882	0.967
F64	8	0.863	0.952
F227	8	0.851	0.963
D244	8	0.850	0.928
D138	8	0.820	0.911
H483	8	0.806	0.882
W289	7	0.972	0.995
C618	7	0.972	0.991
W573	7	0.971	0.994
C629	7	0.968	0.986
C90	7	0.966	0.985

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	0.00053
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000818

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	green

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 phenotypes (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:

Study	Trait	p-value
GCST90000025_723	Appendicular lean mass	6e-29
GCST90002382_6	Eosinophil percentage of white cells	6e-10
GCST006661_290	Male-pattern baldness	1e-8
GCST008129_43	Body mass index	1e-8
GCST003475_3	Beard thickness	4e-7

EFO canonical traits (from GWAS)

3 canonical traits:

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

MeSH disease descriptors

2 disease descriptors:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MASP2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
NARSOPLIMAB	Antibody	3

PharmGKB: 1 entry (CPIC guideline: no)

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)

411 measured of 667 human assays (673 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-25-(4-aminobutyl)-49-benzyl-4,19-bis[(2S)-butan-2-yl]-34-(3-carbamimidamidopropyl)-28-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecaazapentacyclo[29.20.4.0^{7,11}.0^{13,17}.0^{43,47}]pentapentacontan-40-yl]acetic acid	KI	0.15 nM
CHEMBL6152811	IC50	2.2 nM
CHEMBL6166990	IC50	2.9 nM
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,40S,47S,50S,56S)-40-amino-4,34,56-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-37,59,59-trimethyl-3,6,12,18,21,24,27,30,33,36,39,45,49,55,58-pentadecaoxo-60,61-dithia-2,5,11,17,20,23,26,29,32,35,38,44,48,54,57-pentadecazapentacyclo[29.27.4.07,11.013,17.050,54]dohexacontane-47-carboxamide	IC50	3.1 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,44S)-37-amino-4,34,44-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-47,47-dimethyl-3,6,12,18,21,24,27,30,33,36,43,46-dodecaoxo-48,49-dithia-2,5,11,17,20,23,26,29,32,35,42,45-dodecazatetracyclo[29.15.4.07,11.013,17]pentacontan-25-yl]propyl]guanidine	IC50	3.25 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,42S,45S,51S)-4,34,51-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-54,54-dimethyl-3,6,12,18,21,24,27,30,33,36,41,44,50,53-tetradecaoxo-55,56-dithia-2,5,11,17,20,23,26,29,32,35,40,43,49,52-tetradecazapentacyclo[29.22.4.07,11.013,17.045,49]heptapentacontan-42-yl]acetic acid	IC50	4.1 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6147067	IC50	4.7 nM
CHEMBL6172668	IC50	4.7 nM
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,40S,47S,50S)-40-amino-4,34,56-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-2,37-dimethyl-3,6,12,18,21,24,27,30,33,36,39,45,49,55,58-pentadecaoxo-60,61-dithia-2,5,11,17,20,23,26,29,32,35,38,44,48,54,57-pentadecazapentacyclo[29.27.4.07,11.013,17.050,54]dohexacontane-47-carboxamide	IC50	4.7 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,40S,43S,49S)-37,40-bis(aminomethyl)-4,34,49-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-52,52-dimethyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-25-yl]propyl]guanidine	IC50	5 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6161113	IC50	5.5 nM
2-[3-[(1R,4S,7S,9S,14S,17S,23S,26S,29S,32S,35R,38S,41S,44S,47S,53S)-41,44-bis(aminomethyl)-4,38,53-tris[(2S)-butan-2-yl]-26,32-bis(hydroxymethyl)-56,56-dimethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,46,52,55-tetradecaoxo-57,58-dithia-2,5,15,21,24,27,30,33,36,39,42,45,51,54-tetradecazahexacyclo[33.20.4.07,15.09,14.017,21.047,51]nonapentacontan-29-yl]propyl]guanidine	IC50	5.7 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,9S,14S,17S,23S,26S,29S,32S,35R,38S,41S,46S,50S,53S,59S)-4,38,59-tris[(2S)-butan-2-yl]-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-41,46,62,62-tetramethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,45,48,52,58,61-hexadecaoxo-63,64-dithia-2,5,15,21,24,27,30,33,36,39,42,44,47,51,57,60-hexadecazahexacyclo[33.26.4.07,15.09,14.017,21.053,57]pentahexacontane-50-carboxamide	IC50	5.9 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,43S,46R,49S,55S)-4,34,55-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-43,58,58-trimethyl-3,6,12,18,21,24,27,30,33,36,39,42,45,48,54,57-hexadecaoxo-59,60-dithia-2,5,11,17,20,23,26,29,32,35,38,41,44,47,53,56-hexadecazapentacyclo[29.26.4.07,11.013,17.049,53]henhexacontan-46-yl]acetic acid	IC50	6 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,49S)-4,34-bis[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22-(hydroxymethyl)-28-(methoxymethyl)-57,57-dimethyl-3,6,12,18,21,24,27,30,33,36,42,48,54,56-tetradecaoxo-58,59-dithia-2,5,11,17,20,23,26,29,32,35,41,47,53,55-tetradecazahexacyclo[29.25.4.237,40.07,11.013,17.049,53]dohexaconta-37,39,61-trien-25-yl]propyl]guanidine	IC50	6.1 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,44S,50S)-4,34,50-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-53,53-dimethyl-3,6,12,18,21,24,27,30,33,36,43,49,52-tridecaoxo-54,55-dithia-2,5,11,17,20,23,26,29,32,35,42,48,51-tridecazapentacyclo[29.21.4.07,11.013,17.044,48]hexapentacontan-25-yl]propyl]guanidine	IC50	6.3 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,13S,19S,22S,27S,30S,33S,36S,45S)-4,33,45-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,27-bis(hydroxymethyl)-36,48,48-trimethyl-49,50-dithia-2,5,11,17,20,23,25,28,31,34,37,43,46-tridecazatetracyclo[28.17.3.07,11.013,17]pentacontane-3,6,12,18,21,24,26,29,32,35,38,44,47-tridecone	IC50	6.3 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,9S,14S,17R,23S,26S,29S,32S,35R,38S,41S,52S,55S,61S)-4,38,61-tris[(2S)-butan-2-yl]-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-41,64,64-trimethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,50,54,60,63-pentadecaoxo-65,66-dithia-2,5,15,21,24,27,30,33,36,39,42,49,53,59,62-pentadecazahexacyclo[33.28.4.07,15.09,14.017,21.055,59]heptahexacontane-52-carboxamide	IC50	6.7 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,47S,53S)-4,34,53-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-37,56,56-trimethyl-3,6,12,18,21,24,27,30,33,36,39,46,52,55-tetradecaoxo-57,58-dithia-2,5,11,17,20,23,26,29,32,35,38,45,51,54-tetradecazapentacyclo[29.24.4.07,11.013,17.047,51]nonapentacontan-25-yl]propyl]guanidine	IC50	6.75 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6147698	IC50	6.9 nM
(1R,4S,10S,13S,29S,32R,35S,38S,41S,44S,50S,56S,59S)-4,29,59-tris[(2S)-butan-2-yl]-38-[3-(diaminomethylideneamino)propyl]-44-(2,2-dimethylpropyl)-35,41-bis(hydroxymethyl)-61-methyl-2,5,11,15,23,27,30,33,36,39,42,45,51,57,60-pentadecaoxo-63,64-dithia-3,6,12,16,24,28,31,34,37,40,43,46,52,58,61-pentadecazapentacyclo[30.29.4.06,10.046,50.052,56]pentahexacontane-13-carboxamide	IC50	7.1 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,9S,18S,24S,27S,30S,33S,36R,39S,50S,53S,59S)-4,39,59-tris[(2S)-butan-2-yl]-30-[3-(diaminomethylideneamino)propyl]-27,33-bis(hydroxymethyl)-62,62-dimethyl-24-(2-methylpropyl)-3,6,17,23,26,29,32,35,38,41,47,52,58,61-tetradecaoxo-63,64-dithia-2,5,16,22,25,28,31,34,37,46,51,57,60-tridecazahexacyclo[34.25.4.07,16.09,15.018,22.053,57]pentahexacontane-50-carboxamide	IC50	7.2 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6142574	IC50	7.4 nM
CHEMBL6169123	IC50	7.5 nM
CHEMBL6169003	IC50	7.9 nM
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,44S)-4,34,44-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-47,47-dimethyl-3,6,12,18,21,24,27,30,33,36,43,46-dodecaoxo-48,49-dithia-2,5,11,17,20,23,26,29,32,35,42,45-dodecazatetracyclo[29.15.4.07,11.013,17]pentacontan-25-yl]propyl]guanidine	IC50	7.9 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1S,4S,7S,13S,19S,22S,25S,28S,32R,38R,44S)-38-amino-35-butan-2-yl-4,44-bis[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-47,47-dimethyl-3,6,12,18,21,24,27,31,34,37,43,46-dodecaoxo-48,49-dithia-2,5,11,17,20,23,26,33,36,42,45-undecazatetracyclo[30.14.4.07,11.013,17]pentacontan-25-yl]propyl]guanidine	IC50	8.1 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,13S,19S,22S,25S,28S,31R,34S,42S,45R,48S,54S)-4,34,54-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-2,42-dimethyl-3,6,12,18,21,24,27,30,33,36,38,41,44,47,53,56-hexadecaoxo-58,59-dithia-2,5,11,17,20,23,26,29,32,35,37,40,43,46,52,55-hexadecazatetracyclo[29.25.4.013,17.048,52]hexacontan-45-yl]acetic acid	IC50	8.2 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,7S,9S,14S,17S,23S,26S,29S,32S,35R,38S,47S,50S,53S,59S)-4,38,59-tris[(2S)-butan-2-yl]-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-47,62,62-trimethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,46,49,52,58,61-hexadecaoxo-63,64-dithia-2,5,15,21,24,27,30,33,36,39,42,45,48,51,57,60-hexadecazahexacyclo[33.26.4.07,15.09,14.017,21.053,57]pentahexacontan-50-yl]acetic acid	IC50	8.4 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6145812	IC50	8.5 nM
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,47S,53S)-4,34,53-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-38,56,56-trimethyl-3,6,12,18,21,24,27,30,33,36,39,46,52,55-tetradecaoxo-57,58-dithia-2,5,11,17,20,23,26,29,32,35,38,45,51,54-tetradecazapentacyclo[29.24.4.07,11.013,17.047,51]nonapentacontan-25-yl]propyl]guanidine	IC50	8.5 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,43S,46S,49S,55S)-4,34,55-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-43,58,58-trimethyl-3,6,12,18,21,24,27,30,33,36,39,42,45,48,54,57-hexadecaoxo-59,60-dithia-2,5,11,17,20,23,26,29,32,35,38,41,44,47,53,56-hexadecazapentacyclo[29.26.4.07,11.013,17.049,53]henhexacontan-46-yl]acetic acid	IC50	8.6 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,42S,45S,51S)-4,34,51-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-2-methyl-3,6,12,18,21,24,27,30,33,36,41,44,50,53-tetradecaoxo-55,56-dithia-2,5,11,17,20,23,26,29,32,35,40,43,49,52-tetradecazapentacyclo[29.22.4.07,11.013,17.045,49]heptapentacontan-42-yl]acetic acid	IC50	8.7 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,43S,49S)-4,34,49-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-52,52-dimethyl-3,6,12,18,21,24,27,30,33,36,42,48,51-tridecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,41,47,50-tridecazahexacyclo[29.20.4.07,11.013,17.037,41.043,47]pentapentacontan-25-yl]propyl]guanidine	IC50	9 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,45S,48S,54S)-4,34,54-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-37,57,57-trimethyl-3,6,12,18,21,24,27,30,33,36,39,44,47,53,56-pentadecaoxo-58,59-dithia-2,5,11,17,20,23,26,29,32,35,38,43,46,52,55-pentadecazapentacyclo[29.25.4.07,11.013,17.048,52]hexacontan-45-yl]acetic acid	IC50	9.1 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,47S)-4,34,47-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-38,50,50-trimethyl-3,6,12,18,21,24,27,30,33,36,39,46,49-tridecaoxo-51,52-dithia-2,5,11,17,20,23,26,29,32,35,38,45,48-tridecazatetracyclo[29.18.4.07,11.013,17]tripentacontan-25-yl]propyl]guanidine	IC50	9.4 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6143502	IC50	9.5 nM
(1R,4S,7S,9S,14S,17S,23S,26S,29S,32S,35R,53S,58S)-4,38,58-tris[(2S)-butan-2-yl]-56-butyl-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-41,61,61-trimethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,42,45,51,55,57,60-hexadecaoxo-62,63-dithia-2,5,15,21,24,27,30,33,36,39,41,44,50,54,56,59-hexadecazapentacyclo[33.25.4.07,15.09,14.017,21]tetrahexacontane-53-carboxamide	IC50	9.7 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,9S,14S,17S,23S,26S,29S,32S,35R,38S,44S,54S,57S,63S)-44-amino-4,38,63-tris[(2S)-butan-2-yl]-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-66,66-dimethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,47,56,62,65-pentadecaoxo-67,68-dithia-2,5,15,21,24,27,30,33,36,39,42,48,55,61,64-pentadecazahexacyclo[33.30.4.07,15.09,14.017,21.057,61]nonahexacontane-54-carboxamide	IC50	9.8 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,46S,49S,55S)-4,34,55-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-58,58-dimethyl-3,6,12,18,21,24,27,30,33,36,39,44,48,54,57-pentadecaoxo-59,60-dithia-2,5,11,17,20,23,26,29,32,35,38,43,47,53,56-pentadecazapentacyclo[29.26.4.07,11.013,17.049,53]henhexacontane-46-carboxamide	IC50	10 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4R,7S,19S,22S,25S,28S,31R,34S,37R,44S)-37-amino-4,34,44-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-47,47-dimethyl-3,6,12,18,21,24,27,30,33,36,43,46-dodecaoxo-48,49-dithia-2,5,11,17,20,23,26,29,32,35,42,45-dodecazatricyclo[29.15.4.07,11]pentacontan-25-yl]propyl]guanidine	IC50	10 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL4242095	KI	11 nM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,37S,48S,51S,57S)-4,34,57-tris[(2S)-butan-2-yl]-25-[3-(diaminomethylideneamino)propyl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-37,60,60-trimethyl-3,6,12,18,21,24,27,30,33,36,39,47,50,56,59-pentadecaoxo-42,44-dioxa-61,62-dithia-2,5,11,17,20,23,26,29,32,35,38,46,49,55,58-pentadecazapentacyclo[29.28.4.07,11.013,17.051,55]trihexacontan-48-yl]acetic acid	IC50	11 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,51S,57S)-4,34,57-tris[(2S)-butan-2-yl]-19-(2,2-dimethylpropyl)-22,28-bis(hydroxymethyl)-60,60-dimethyl-3,6,12,18,21,24,27,30,33,36,43,50,56,59-tetradecaoxo-61,62-dithia-2,5,11,17,20,23,26,29,32,35,42,49,55,58-tetradecazahexacyclo[29.28.4.237,40.07,11.013,17.051,55]pentahexacontan-25-yl]propyl]guanidine	IC50	11 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
(1R,4S,7S,9S,14R,17S,23S,26S,29S,32S,35R,38S,41S,53S,56S,62S)-4,38-bis[(2S)-butan-2-yl]-62-[(2R)-butan-2-yl]-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-41,42,65,65-tetramethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,46,51,55,61,64-hexadecaoxo-66,67-dithia-2,5,15,21,24,27,30,33,36,39,42,45,50,54,60,63-hexadecazahexacyclo[33.29.4.07,15.09,14.017,21.056,60]octahexacontane-53-carboxamide	IC50	11 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
2-[3-[(1R,4S,9S,15S,18S,21S,24S,27S,30S,33R,40S)-33-amino-4,30,40-tris[(2S)-butan-2-yl]-7-butyl-15-(2,2-dimethylpropyl)-18,24-bis(hydroxymethyl)-43-methyl-3,6,8,14,17,20,23,26,29,32,39,42-dodecaoxo-44,45-dithia-2,5,7,13,16,19,22,25,28,31,38,41-dodecazatricyclo[25.15.3.09,13]pentatetracontan-21-yl]propyl]guanidine	IC50	11 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
methyl (2S,3S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2S,3aS,7aS)-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2S)-2-(6-aminohexanoylamino)propanoyl]amino]-3-methylpentanoyl]amino]-3-tritylsulfanylpropanoyl]amino]-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]-5-[[N-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonyl]carbamimidoyl]amino]pentanoyl]amino]-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]amino]-3-methylpentanoyl]amino]-3-tritylsulfanylpropanoyl]amino]-3-methylpentanoate	IC50	12 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF
CHEMBL6165656	IC50	13 nM
CHEMBL6175367	IC50	13 nM
(1R,4S,7S,9S,14S,17S,23S,26S,29S,32S,35R,38S,46S,50S,53S,59S)-4,38,59-tris[(2S)-butan-2-yl]-29-[3-(diaminomethylideneamino)propyl]-26,32-bis(hydroxymethyl)-46,62,62-trimethyl-23-(2-methylpropyl)-3,6,16,22,25,28,31,34,37,40,43,45,48,52,58,61-hexadecaoxo-63,64-dithia-2,5,15,21,24,27,30,33,36,39,42,44,47,51,57,60-hexadecazahexacyclo[33.26.4.07,15.09,14.017,21.053,57]pentahexacontane-50-carboxamide	IC50	13 nM	US-20240010684: MASP INHIBITORY COMPOUNDS AND USES THEREOF

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

40 with measured affinity, of 43 total; 37 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
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-[[(1R)-1-phenylethyl]amino]phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0022	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-[(4-chlorophenyl)sulfonylamino]phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0029	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-(benzenesulfonamido)phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0040	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-[[(1S)-1-phenylethyl]amino]phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0047	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-(benzenesulfonamido)cyclohexyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0047	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-[(3,5-dimethylphenyl)sulfonylamino]-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0055	uM
(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
N-[[4-(2-amino-1H-imidazol-5-yl)-2-fluorophenyl]methyl]-2-[4-(benzenesulfonamido)phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0069	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-[(4-propan-2-ylphenyl)sulfonylamino]phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0074	uM
N-[[4-(2-amino-1H-imidazol-5-yl)-3-methoxyphenyl]methyl]-2-[4-(benzenesulfonamido)phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0075	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-[(4-chlorophenyl)sulfonylamino]-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0079	uM
N-[[4-(2-amino-1H-imidazol-5-yl)-2-methylphenyl]methyl]-2-[4-(benzenesulfonamido)phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0085	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-(benzenesulfonamido)-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0090	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-[(4-propan-2-ylphenyl)sulfonylamino]-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0095	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[5-(benzenesulfonamido)pyrimidin-2-yl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0114	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-(benzenesulfonamido)-2-methoxy-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0125	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-(benzylamino)phenyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0127	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-(benzenesulfonamido)-2-methyl-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0160	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[2-(benzenesulfonamido)spiro[3.3]heptan-6-yl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0175	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-(4-phenylmethoxyphenyl)acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0300	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-[(1-methylpyrazol-4-yl)sulfonylamino]-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0454	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-[(4-methoxyphenyl)sulfonylamino]-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0463	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-[(3-propan-2-ylphenyl)sulfonylamino]-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0683	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[6-(oxan-4-ylsulfonylamino)-3-pyridinyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.0952	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[2-(benzenesulfonamido)pyrimidin-5-yl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.1170	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-3-phenylpropanamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.1240	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[(1S,3R)-4-(benzenesulfonamido)-2-bicyclo[1.1.1]pentanyl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.1250	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-phenylacetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.1550	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
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-[4-(benzenesulfonamido)piperidin-1-yl]acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.2060	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
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-(6-amino-3-pyridinyl)acetamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.2570	uM
cis-(1R,2S)-N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]-2-phenylcyclopropane-1-carboxamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.3230	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
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]benzamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	0.9760	uM
N-[[4-(2-amino-1H-imidazol-5-yl)phenyl]methyl]cyclopropanecarboxamide	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	1.7400	uM
5-phenyl-1H-imidazol-2-amine	2237337: Inhibition of human MASP-2 (287 to 686 residues) using Z-Lys-SBzl as substrate incubated for 1 hr by plate reader based analysis	ic50	3.1000	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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MASP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.