MBL2

Summary

MBL2 (mannose binding lectin 2, HGNC:6922) is a protein-coding gene on chromosome 10q21.1, encoding Mannose-binding protein C (P11226). Calcium-dependent lectin, which acts as a pattern recognition receptor that initiates 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 the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases.

Source: NCBI Gene 4153 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mannose-binding lectin deficiency (Limited, GenCC)
• GWAS associations: 38
• Clinical variants (ClinVar): 130 total — 1 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_001378373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6922
Approved symbol	MBL2
Name	mannose binding lectin 2
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	COLEC1, MBP-C, MBP1, MBP
Ensembl gene	ENSG00000165471
Ensembl biotype	protein_coding
OMIM	154545
Entrez	4153

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000373968, ENST00000674931, ENST00000675947, ENST00000877442, ENST00000877443

RefSeq mRNA: 3 — MANE Select: NM_001378373 NM_000242, NM_001378373, NM_001378374

CCDS: CCDS7247

Canonical transcript exons

ENST00000674931 — 5 exons

Exon	Start	End
ENSE00001462026	52765380	52768510
ENSE00003532948	52770670	52770786
ENSE00003552596	52769247	52769315
ENSE00003900343	52771449	52771644
ENSE00003900486	52772737	52772784

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 95.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8352 / max 266.7529, expressed in 20 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109402	0.3687	10
109403	0.2392	12
109400	0.1191	11
109399	0.1003	12
109401	0.0079	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.84	gold quality
liver	UBERON:0002107	95.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.53	silver quality
buccal mucosa cell	CL:0002336	79.12	gold quality
adrenal tissue	UBERON:0018303	69.89	gold quality
cerebellar vermis	UBERON:0004720	52.38	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.10	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.32	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
thymus	UBERON:0002370	50.11	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelial cell of pancreas	CL:0000083	48.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
deltoid	UBERON:0001476	48.26	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ENO1, MYC, PPARA

miRNA regulators (miRDB)

145 targeting MBL2, 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-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• MBL mutants show enhanced susceptibility to proteolysis by matrix metalloproteinases (PMID:11891230)
• MBL significantly enhances the binding of C4 to Staphylococcus aureus over the course of 10 min in sera from MBL-deficient donors. (PMID:12370377)
• Point mutations of MBL2 are associated with celiac disease. (PMID:12439623)
• mutation of the MBL gene might influence the clinical outcome of HBV infection in Vietnamese patients (PMID:12517417)
• study shows that specific alterations of the N-linked carbohydrates on HIV gp120/gp41 can enhance MBL-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL (PMID:12560567)
• This protein is a biological marker of disease progrsesion in HIV infection and HAART. (PMID:12640191)
• Polymorphisms in the MBL2 gene reduce serum MBL levels in chronic obstructive pulmonary disease patients and are associated with risk of infection. (PMID:12761563)
• Serum levels are reduced in Behcet’s disease (PMID:12918709)
• low expression of MBL genotype XA/0 may be associated with protection abainst TB whereas high-expression genotypes and gentoypes conferring MBL deficiency are not (PMID:12934195)
• studies show that mannose-binding lectin deficiency is an inherited characteristic and may be a crucial factor in maintaining immunologic health (PMID:14582818)
• Mutations in the collagenous region of human MBL compromise assembly of higher order oligomers, resulting in reduced ligand binding capacity and thus reduced capability to activate complement. (PMID:14764589)
• Polymorphism within the MBL gene is not associated with presence or extent of erosions by 5 years in patients with rheumatoid arthritis or inflammatory polyarthritis. (PMID:14994386)
• The protective effect of the B allele of the MBL gene against tuberculosis was found in African Americans but not other ethnicities. (PMID:15061663)
• mannose-binding lectin-2 exon 1 polymorphisms with low serum levels of functional MBL protein are associated with a greatly increased risk of developing systemic inflammatory response syndrome (SIRS. (PMID:15127191)
• MBL genotype modulates arterial stiffness, an important cardiovascular risk factor, in children after Kawasaki disease (PMID:15295097)
• MBL interacts with non-LPS components of N. meningitidis and modulates the cytokine response (PMID:15381182)
• pregnant women bearing the G54D MBL allele have a greater risk for developing gestational diabetes mellitus and having heavier infants (PMID:15472209)
• review of role of mannose binding lectin in the innate immune system via interaction with HIV gp120 (PMID:15488604)
• MBL2 variants, responsible for lower MBL levels, are associated with celiac disease and higher risk of developing autoimmune diseases (PMID:15645196)
• the polypeptide dimer is the basic unit in the oligomerization of mannan-binding lectin. (PMID:15653690)
• A previously unrecognized feature of mannose binding lectin is the presence of a highly stable collagen triple-helix adjacent to a much less stable triple helix, which may have imperfect hydrogen bonding making little enthalpic contributions. (PMID:15697204)
• MBL2 contains 12 disulfide-linked chains and is tetrameric in structure; the oligomerization state of MBL has a direct effect on its carbohydrate-binding properties, but no influence on the interaction with MBL-associated serine proteases (MASPs). (PMID:15728497)
• Mannose-binding lectin polymorphism associated with increased prevalence of bacterial infection in critically ill adults (PMID:15753758)
• Mannose-binding lectin alleles are associated with restenosis in patients undergoing carotid eversion endarterectomy. (PMID:15790942)
• The role of mannose-binding lectin (MBL2) in natural immunity to SARS-CoV infection is reported. (PMID:15838797)
• increased blood levels in asthmatic children; findings indicate that mbl may be implicated in the pathogenesis of asthma by contributing to airway inflammation or by increasing the risk of developing asthma (PMID:15853952)
• Complement activation initiated by MBL may be involved in the pathogenesis of diabetic microvascular complications. (PMID:15855341)
• Higher MBL levels seem to be associated with a more severe form of rejection leading to treatment failure and graft loss (PMID:15888042)
• The CGT52TGT point mutation of MBL gene does not affect the secretion of its product, but a Cys introduced by the mutation could form another disulfide bond which may disrupt the structure of MBL molecule as well as its function. (PMID:15989776)
• functional serum mannose-binding lectin (MBL) activating capacity of five isolates of Moraxella catarrhalis obtained from children who suffered recurrent acute otitis media episodes (PMID:16006058)
• Mannose-binding lectin (MBL) inhibits peptidoglycan (PGN)-mediated tumor necrosis factor-alpha production and enhances secretion of chemokines by macrophages, hence MBL may down-regulate PGN-mediated inflammation while enhancing phagocyte recruitment (PMID:16034120)
• Significantly earlier age at onset of Pseudomonas aeruginosa colonisation was found in CF patients with at least one MBL2 variant. (PMID:16046196)
• The present study reveals native, oligomeric forms of human MBL in plasma from healthy blood donors of differing genotypes and correlates the relative abundance of observed molecular weight species with mannan binding activity and C4 deposition in vitro. (PMID:16099048)
• binds to Ebola and Marburg envelope glycoproteins during infection in humans and inhibits ENV interaction with DC-SIGN (PMID:16099912)
• On average, high MASP-1 correlates with low MASP-2 and vice-versa, and confirms the hypothesis that native MBL-MASP complexes on average do not have fixed MBL-(MASP-1)-(MASP-2) stoichiometry. (PMID:16102832)
• Low-producing MBL2 variants and low MBL levels are associated with increased susceptibility to and severity of a variety of infective illnesses (PMID:16105157)
• mbl2 gene expression may be relevant in local immune defense, particularly in restricted areas of the gastrointestinal and reproductive tracts. (PMID:16112196)
• Mannose binding lectin (MBL) is a calcium dependent C-type lectin that acts as an important first line defence mechanism against infection by its capability to activate the complement system and enhance phagocytosis. (PMID:16115848)
• MBL gene mutations may not be a main factor of the pathogenesis of chronic rheumatic heart disease, but MBL deficiency may facilitate the development of CRHD in younger people. (PMID:16200716)
• additional 5’ variants as well as markers of distinct 3’ haplotype blocks in MBL2 may contribute to circulating mannose-binding protein levels (PMID:16208516)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	col7a1	ENSDARG00000021720
danio_rerio	hbl4	ENSDARG00000054202
danio_rerio	mbl2	ENSDARG00000068220
danio_rerio	hbl1	ENSDARG00000068221
danio_rerio	hbl2	ENSDARG00000094681
mus_musculus	Mbl2	ENSMUSG00000024863
rattus_norvegicus	AABR07006691.1	ENSRNOG00000011637

Protein

Protein identifiers

Mannose-binding protein C — P11226 (reviewed: P11226)

Alternative names: Collectin-1, MBP1, Mannan-binding protein, Mannose-binding lectin

All UniProt accessions (1): P11226

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent lectin, which acts as a pattern recognition receptor that initiates 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. Specifically recognizes and binds the mannose moiety of carbohydrates on the pathogen surface, activating the MASP1 serine protease and initiating the proteolytic cascade of the lectin complement pathway. Upon SARS coronavirus-2/SARS-CoV-2 infection, activates the complement lectin pathway which leads to the inhibition SARS-CoV-2 infection and a reduction of the induced inflammatory response. May bind DNA.

Subunit / interactions. Oligomeric complex of 3 or more homotrimers. Interacts with MASP1 and MASP2. Interacts with MEP1A and MEP1B and may inhibit their catalytic activity. Interacts with CR1 (via Sushi 24 and Sushi 25 domains). (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 Spike glycoprotein homotrimer; the interaction is calcium-dependent and modulated by Spike glycoprotein glycosylation state.

Subcellular location. Secreted. Cell surface.

Tissue specificity. Plasma protein produced mainly in the liver.

Domain organisation. The coiled-coil domain mediates trimerization.

Polymorphism. Genetic variations in MBL2 influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]. Genetic variations in MBL2 may influence susceptibility to severe COVID-19 disease caused by SARS-CoV-2 virus infection. Genetic variations in MBL2 are responsible for mannose-binding protein deficiency [MIM:614372]. This condition is defined as MBL2 protein level of less than 100 ng/ml, is present in about 5% of people of European descent and in about 10% of sub-Saharan Africans. Most MBL2-deficient adults appear healthy, but low levels of MBL2 are associated with increased risk of infection in toddlers, in cancer patients undergoing chemotherapy, and in organ-transplant patients receiving immunosuppressive drugs, particularly recipients of liver transplants. There is an association between low levels of MBL2 and a defect of opsonization which results in susceptibility to frequent and chronic infections. Functional MBL2 deficiency may be associated with protection against tuberculosis caused by Mycobacterium africanum but not by Mycobacterium tuberculosis, as observed in studies on Ghanaian patients with pulmonary tuberculosis.

RefSeq proteins (3): NP_000233, NP_001365302, NP_001365303 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR008160	Collagen	Repeat
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033990	Collectin_CTLD	Domain
IPR051077	Ca-dependent_lectin	Family

Pfam: PF00059, PF01391

UniProt features (50 total): binding site 18, strand 7, modified residue 5, sequence variant 5, helix 4, compositionally biased region 3, domain 2, disulfide bond 2, signal peptide 1, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1HUP	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11226-F1	82.59	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (18): 192; 209; 210; 212; 212; 214; 214; 215; 220; 220; 220; 221 …

Post-translational modifications (5): 47, 73, 79, 82, 88

Disulfide bonds (2): 155–244, 222–236

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-166662	Lectin pathway of complement activation
R-HSA-166663	Initial triggering of complement
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses
R-HSA-1643685	Disease
R-HSA-166658	Complement cascade
R-HSA-166786	Creation of C4 and C2 activators
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 569 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, SHEPARD_BMYB_MORPHOLINO_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_COLLAGEN_TRIMER, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOCC_CELL_SURFACE, chr10q21, GOBP_VESICLE_MEDIATED_TRANSPORT, LEE_LIVER_CANCER_CIPROFIBRATE_DN, CAGCTG_AP4_Q5, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY

GO Biological Process (22): complement activation, lectin pathway (GO:0001867), cell surface pattern recognition receptor signaling pathway (GO:0002752), proteolysis (GO:0006508), acute-phase response (GO:0006953), complement activation, classical pathway (GO:0006958), response to oxidative stress (GO:0006979), opsonization (GO:0008228), defense response to bacterium (GO:0042742), surfactant homeostasis (GO:0043129), innate immune response (GO:0045087), negative regulation of viral process (GO:0048525), positive regulation of phagocytosis (GO:0050766), defense response to Gram-positive bacterium (GO:0050830), obsolete killing by host of symbiont cells (GO:0051873), antiviral innate immune response (GO:0140374), positive regulation of opsonization (GO:1903028), activation of membrane attack complex (GO:0001905), immune system process (GO:0002376), complement activation (GO:0006956), zymogen activation (GO:0031638), killing of cells of another organism (GO:0031640), protein maturation (GO:0051604)

GO Molecular Function (7): signaling receptor binding (GO:0005102), D-mannose binding (GO:0005537), pattern recognition receptor activity (GO:0038187), identical protein binding (GO:0042802), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (8): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), multivesicular body (GO:0005771), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), symbiont cell surface (GO:0106139), serine-type endopeptidase complex (GO:1905370)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Creation of C4 and C2 activators	1
Complement cascade	1
SARS-CoV-2-host interactions	1
Dengue Virus-Host Interactions	1
Innate Immune System	1
Initial triggering of complement	1
Immune System	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	3
protein binding	3
innate immune response	2
immune effector process	2
binding	2
cellular anatomical structure	2
innate immune response activating cell surface receptor signaling pathway	1
pattern recognition receptor signaling pathway	1
protein metabolic process	1
acute inflammatory response	1
humoral immune response mediated by circulating immunoglobulin	1
response to stress	1
phagocytosis, recognition	1
defense response	1
response to bacterium	1
multicellular organismal-level chemical homeostasis	1
immune response	1
defense response to symbiont	1
viral process	1
negative regulation of biological process	1
regulation of viral process	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
defense response to bacterium	1
defense response to virus	1
positive regulation of immune effector process	1
opsonization	1
positive regulation of phagocytosis	1
regulation of opsonization	1
biological_process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
protein processing	1
monosaccharide binding	1
signaling receptor activity	1
calcium ion binding	1
protein-containing complex	1
late endosome	1

Protein interactions and networks

STRING

1560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBL2	FCN2	Q15485	994
MBL2	MASP2	O00187	994
MBL2	PRSS2	P07478	991
MBL2	F8W876	F8W876	974
MBL2	CALR	P27797	974
MBL2	FCN3	O75636	965
MBL2	PTX3	P26022	965
MBL2	COLEC11	Q9BWP8	874
MBL2	FCN1	O00602	863
MBL2	C3	P01024	851
MBL2	CD209	Q9NNX6	834
MBL2	CRP	P02741	833
MBL2	C1R	P00736	824
MBL2	C1S	P09871	823
MBL2	C4A	P01028	810

IntAct

133 interactions, top by confidence:

A	B	Type	Score
	MBL2	psi-mi:“MI:0914”(association)	0.940
	MBL2	psi-mi:“MI:0915”(physical association)	0.940
	MBL2	psi-mi:“MI:0407”(direct interaction)	0.940
MASP1	MBL2	psi-mi:“MI:0915”(physical association)	0.920
MBL2	MASP1	psi-mi:“MI:0407”(direct interaction)	0.920
MASP1	MBL2	psi-mi:“MI:0407”(direct interaction)	0.920
MBL2	MBL2	psi-mi:“MI:0407”(direct interaction)	0.870

BioGRID (33): TRAPPC2 (Affinity Capture-Western), MBL2 (Affinity Capture-Western), UBQLN2 (Two-hybrid), CALR (Reconstituted Complex), SLTM (Proximity Label-MS), MBL2 (Affinity Capture-Western), MASP2 (Affinity Capture-Western), MASP1 (Affinity Capture-Western), MBL2 (Reconstituted Complex), TRMU (Affinity Capture-MS), MBL2 (Affinity Capture-MS), PSMA1 (Affinity Capture-MS), PSMA2 (Affinity Capture-MS), PSMA3 (Affinity Capture-MS), PSMA6 (Affinity Capture-MS)

ESM2 similar proteins: B1A4N2, B1A4P2, B1A4P8, B1A4Q3, B1A4Q5, C0STK6, O02659, P06908, P08427, P08661, P11226, P12842, P19999, P23805, P35242, P35247, P35248, P39039, P41317, P42916, P49874, P50403, P50404, Q1PBC5, Q2LK95, Q5M8X6, Q5U9S1, Q66S37, Q66S41, Q66S45, Q66S50, Q66S54, Q66S58, Q66S60, Q66S61, Q66S62, Q66S63, Q66S64, Q66S65, Q6RXL1

Diamond homologs: A5PMY6, A6QP79, D3ZWT9, O14594, P02706, P02707, P05451, P06734, P07306, P07307, P07897, P07898, P08290, P08661, P10716, P10758, P11226, P13608, P13611, P16112, P19999, P20693, P22897, P24721, P34927, P41317, P43137, P48304, P49300, P49301, P55066, P55067, P60883, P70194, P81282, P82596, P86854, Q28343, Q28670, Q29011

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MBL2	“down-regulates activity”	S	binding
MBL2	“up-regulates activity”	MASP1	binding
MBL2	“up-regulates activity”	MASP2	binding
PAMPs	“up-regulates activity”	MBL2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	101
Likely benign	17
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3063125	GRCh37/hg19 10q21.1(chr10:54459920-56080457)x1	Pathogenic

SpliceAI

1691 predictions. Top by Δscore:

Variant	Effect	Δscore
10:52769246:CA:C	donor_gain	1.0000
10:52771444:CGTA:C	donor_loss	1.0000
10:52771445:GTACC:G	donor_loss	1.0000
10:52771446:TA:T	donor_loss	1.0000
18:76984815:C:CA	donor_gain	1.0000
18:76989954:A:AC	donor_gain	1.0000
18:76989955:C:CC	donor_gain	1.0000
18:77012741:C:CT	acceptor_gain	1.0000
10:52768509:CC:C	acceptor_gain	0.9900
10:52768509:CCCTA:C	acceptor_loss	0.9900
10:52768510:CC:C	acceptor_gain	0.9900
10:52768510:CCTA:C	acceptor_loss	0.9900
10:52768511:C:CC	acceptor_gain	0.9900
10:52768511:CTA:C	acceptor_loss	0.9900
10:52768518:G:C	acceptor_gain	0.9900
10:52769245:A:AC	donor_gain	0.9900
10:52769246:C:CC	donor_gain	0.9900
10:52769246:CACT:C	donor_gain	0.9900
10:52769246:CACTT:C	donor_gain	0.9900
10:52770787:C:CC	acceptor_gain	0.9900
10:52770787:C:G	acceptor_loss	0.9900
10:52770788:T:A	acceptor_loss	0.9900
10:52771466:C:CA	donor_gain	0.9900
18:76980470:CC:C	acceptor_gain	0.9900
18:76980471:CC:C	acceptor_gain	0.9900
18:76984774:CCAG:C	donor_gain	0.9900
18:76989955:CA:C	donor_gain	0.9900
18:77012746:C:CT	acceptor_gain	0.9900
18:77012747:A:T	acceptor_gain	0.9900
18:77016828:TCA:T	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000067088 (10:52773511 G>A), RS1000134067 (10:52772210 C>A,T), RS1000167296 (10:52768037 T>C), RS1000247371 (10:52770965 G>A), RS1000281538 (10:52767710 G>A), RS1000418456 (10:52773279 G>C), RS1001510824 (10:52765626 T>C), RS1001543680 (10:52765336 A>T), RS1001692978 (10:52774637 C>G,T), RS1002181781 (10:52770446 G>A), RS1002518563 (10:52771692 A>G), RS1003082932 (10:52766042 G>A), RS1003214298 (10:52766707 A>C), RS1004307319 (10:52767452 G>A), RS1004338491 (10:52767144 T>C)

Disease associations

OMIM: gene MIM:154545 | disease phenotypes: MIM:614372, MIM:219700

GenCC curated gene-disease

Disease	Classification	Inheritance
mannose-binding lectin deficiency	Limited	Autosomal dominant

Mondo (2): mannose-binding lectin deficiency (MONDO:0013714), cystic fibrosis (MONDO:0009061)

Orphanet (1): Cystic fibrosis (Orphanet:586)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001508	Failure to thrive
HP:0001581	Recurrent skin infections
HP:0002742	Recurrent Klebsiella infections
HP:0005353	Recurrent herpes
HP:0005381	Recurrent meningococcal disease
HP:0031699	Disseminated cryptosporidium infection

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST001482_4	Lumbar spine bone mineral density	2.000000e-12
GCST001814_17	Age-related macular degeneration	3.000000e-06
GCST001814_28	Age-related macular degeneration	2.000000e-06
GCST002333_5	Bone properties (heel)	5.000000e-15
GCST002335_5	Bone properties (heel)	1.000000e-08
GCST002945_14	Emphysema imaging phenotypes	2.000000e-07
GCST003989_2	Chin dimples	2.000000e-08
GCST003996_44	Monobrow	4.000000e-15
GCST004350_17	Bone ultrasound measurement (velocity of sound)	4.000000e-07
GCST004351_9	Bone ultrasound measurement (broadband ultrasound attenuation)	4.000000e-07
GCST005790_18	Rosacea symptom severity	5.000000e-06
GCST005795_29	Femoral neck bone mineral density	1.000000e-06
GCST005796_16	Lumbar spine bone mineral density	2.000000e-08
GCST006288_106	Heel bone mineral density	2.000000e-24
GCST006288_107	Heel bone mineral density	2.000000e-62
GCST006288_108	Heel bone mineral density	2.000000e-12
GCST006288_491	Heel bone mineral density	4.000000e-11
GCST006288_632	Heel bone mineral density	7.000000e-27
GCST006288_633	Heel bone mineral density	9.000000e-67
GCST006288_634	Heel bone mineral density	6.000000e-138
GCST006288_635	Heel bone mineral density	5.000000e-19
GCST006288_717	Heel bone mineral density	1.000000e-40
GCST006288_718	Heel bone mineral density	1.000000e-76
GCST006288_719	Heel bone mineral density	2.000000e-08
GCST006288_766	Heel bone mineral density	3.000000e-15
GCST006423_10	Fracture	1.000000e-32
GCST006585_404	Blood protein levels	0.000000e+00
GCST006979_577	Heel bone mineral density	7.000000e-47
GCST006979_578	Heel bone mineral density	3.000000e-110
GCST006979_579	Heel bone mineral density	4.000000e-41

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005654	velocity of sound measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0007626	emphysema imaging measurement
EFO:0007906	synophrys measurement
EFO:0009180	rosacea severity measurement
EFO:0007785	femoral neck bone mineral density
EFO:0007701	spine bone mineral density
EFO:0009270	heel bone mineral density
EFO:0009771	methionine measurement
EFO:0005001	phenylalanine measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
C563602	Mannose-Binding Protein Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795113 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	6
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression	6
Cyclosporine	affects cotreatment, affects expression, decreases expression	4
Aflatoxin B1	decreases expression, decreases methylation, affects expression	3
sodium arsenite	affects expression, decreases expression	2
perfluorooctane sulfonic acid	increases expression	2
2,4,6-tribromophenol	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
decabromobiphenyl ether	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
tetrabromobisphenol A	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
perfluorooctanoic acid	increases expression	1
cerous chloride	decreases expression, affects cotreatment	1
lanthanum chloride	affects cotreatment, decreases expression	1
benazol P	affects expression	1
perfluorodecanoic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-heptanoic acid	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
perfluorohexanoic acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
perfluorododecanoic acid	decreases expression	1
Bortezomib	increases response to substance	1
Rosiglitazone	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1805068	Binding	Binding affinity to MBP at 1 mM	FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to in vitro and in vivo evaluation. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis