Mannose-binding lectin deficiency

Summary

Mannose-binding lectin deficiency (MONDO:0013714) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 87
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mannose-binding lectin deficiency
Mondo ID	MONDO:0013714
MeSH	C563602
OMIM	614372
SNOMED CT	703538003
UMLS	C3280586
MedGen	482216
GARD	0024941
Is cancer (heuristic)	no

Also known as: mannose-binding lectin deficiency · mannose-binding protein deficiency · MBLD

Data availability: 87 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › complement deficiency › disorder of lectin complement activation pathway › mannose-binding lectin deficiency

Related subtypes (2): immunodeficiency due to MASP-2 deficiency, immunodeficiency due to ficolin3 deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

87 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 9 conflicting classifications of pathogenicity, 9 likely benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14350	NM_001378373.1(MBL2):c.161G>A (p.Gly54Asp)	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14352	NM_001378373.1(MBL2):c.154C>T (p.Arg52Cys)	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300108	NM_001378373.1(MBL2):c.*2450A>T	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300122	NM_001378373.1(MBL2):c.*1695G>T	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300123	NM_001378373.1(MBL2):c.*1694G>T	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300151	NM_001378373.1(MBL2):c.163A>G (p.Thr55Ala)	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
403073	NM_001378373.1(MBL2):c.132C>T (p.Asn44=)	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
631637	NM_001378373.1(MBL2):c.628G>T (p.Glu210Ter)	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
736719	NM_001378373.1(MBL2):c.527A>G (p.Asn176Ser)	MBL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030691	NM_001378373.1(MBL2):c.449A>C (p.Lys150Thr)	MBL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
300104	NM_001378373.1(MBL2):c.*2727G>T	MBL2	Uncertain significance	criteria provided, single submitter
300105	NM_001378373.1(MBL2):c.*2702G>A	MBL2	Uncertain significance	criteria provided, single submitter
300106	NM_001378373.1(MBL2):c.*2477C>T	MBL2	Uncertain significance	criteria provided, single submitter
300107	NM_001378373.1(MBL2):c.*2470A>C	MBL2	Uncertain significance	criteria provided, single submitter
300111	NM_001378373.1(MBL2):c.*2067C>T	MBL2	Uncertain significance	criteria provided, single submitter
300112	NM_001378373.1(MBL2):c.*2066G>T	MBL2	Uncertain significance	criteria provided, single submitter
300115	NM_001378373.1(MBL2):c.*2033G>A	MBL2	Uncertain significance	criteria provided, single submitter
300120	NM_001378373.1(MBL2):c.*1819T>C	MBL2	Uncertain significance	criteria provided, single submitter
300121	NM_001378373.1(MBL2):c.*1711T>G	MBL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
300125	NM_001378373.1(MBL2):c.*1569A>G	MBL2	Uncertain significance	criteria provided, single submitter
300126	NM_001378373.1(MBL2):c.*1568C>T	MBL2	Uncertain significance	criteria provided, single submitter
300127	NM_001378373.1(MBL2):c.*1498C>T	MBL2	Uncertain significance	criteria provided, single submitter
300128	NM_001378373.1(MBL2):c.*1452A>T	MBL2	Uncertain significance	criteria provided, single submitter
300129	NM_001378373.1(MBL2):c.*1429A>C	MBL2	Uncertain significance	criteria provided, single submitter
300130	NM_001378373.1(MBL2):c.*1287C>T	MBL2	Uncertain significance	criteria provided, single submitter
300132	NM_001378373.1(MBL2):c.*1144A>G	MBL2	Uncertain significance	criteria provided, single submitter
300133	NM_001378373.1(MBL2):c.*1136A>G	MBL2	Uncertain significance	criteria provided, single submitter
300134	NM_001378373.1(MBL2):c.*1135A>G	MBL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
300135	NM_001378373.1(MBL2):c.*1134C>T	MBL2	Uncertain significance	criteria provided, single submitter
300136	NM_001378373.1(MBL2):c.*1088C>T	MBL2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MBL2	Limited	Autosomal dominant	mannose-binding lectin deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MBL2	HGNC:6922	ENSG00000165471	P11226	Mannose-binding protein C	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MBL2	Mannose-binding protein C	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 t…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MBL2	Other/Unknown	no		C-type_lectin-like, Collagen, C-type_lectin-like/link_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MBL2	18	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MBL2	1,726

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MBL2	P11226	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Creation of C4 and C2 activators	1	1903.3×	0.006	MBL2
Lectin pathway of complement activation	1	1268.9×	0.006	MBL2
Complement cascade	1	634.4×	0.006	MBL2
Initial triggering of complement	1	601.0×	0.006	MBL2
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.008	MBL2
SARS-CoV-2-host interactions	1	119.0×	0.020	MBL2
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.022	MBL2
SARS-CoV-2 Infection	1	80.4×	0.022	MBL2
SARS-CoV Infections	1	55.4×	0.028	MBL2
Viral Infection Pathways	1	30.8×	0.045	MBL2
Innate Immune System	1	25.5×	0.047	MBL2
Infectious disease	1	24.8×	0.047	MBL2
Disease	1	13.1×	0.077	MBL2
Immune System	1	13.0×	0.077	MBL2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of viral process	1	2808.7×	0.002	MBL2
complement activation, lectin pathway	1	1685.2×	0.002	MBL2
positive regulation of opsonization	1	1685.2×	0.002	MBL2
opsonization	1	1532.0×	0.002	MBL2
cell surface pattern recognition receptor signaling pathway	1	1404.3×	0.002	MBL2
obsolete killing by host of symbiont cells	1	1404.3×	0.002	MBL2
surfactant homeostasis	1	802.5×	0.003	MBL2
complement activation, classical pathway	1	543.6×	0.004	MBL2
acute-phase response	1	421.3×	0.004	MBL2
positive regulation of phagocytosis	1	318.0×	0.005	MBL2
antiviral innate immune response	1	227.7×	0.006	MBL2
response to oxidative stress	1	130.6×	0.010	MBL2
defense response to Gram-positive bacterium	1	127.7×	0.010	MBL2
defense response to bacterium	1	108.0×	0.011	MBL2
proteolysis	1	34.2×	0.030	MBL2
innate immune response	1	33.6×	0.030	MBL2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MBL2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MBL2	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MBL2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MBL2	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05169541	Not specified	RECRUITING	Association Between Plasma Level of Mannose Binding Lectin and Human Reproduction
NCT04017754	Not specified	COMPLETED	Low Plasma Mannose Binding Lectin (p-MBL) Level is a Risk Factor for Recurrent Pregnancy Loss (RPL)