MBL2

protein-coding

mannose binding lectin 2, the group of Complement system activation components|Collectins

Gene summary

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. [provided by RefSeq, Jun 2020]

Previous symbols:

MANE transcript

NM_001378373.1

Inheritance

ClinVar variants

U:49B:14

Top phenotype

Mannose-binding protein deficiency

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr10:52,765,380-52,772,784

External References & Databases

Ensembl (ENSG00000165471)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mannose-binding lectin deficiencyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013714

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Mannose-binding protein deficiencyAD

Manifestation: Biochemical

Intervention: Pharmacogenomic

Rationale: Low MBL levels are associated with increased risk of infection in young children, cancer patients undergoing chemotherapy, and organ-transplant patients treated with immunosuppressive regimens, especially liver transplant recipients

Refs: 21871896

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MBL2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 46

Mannose-binding lectin deficiencyTotal: 22

not providedTotal: 12

MBL2-related disorderTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378373.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	6 clinvar		10
missense			42 clinvar	7 clinvar		49
nonsense				1 clinvar		1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	0	0	49	14	0	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001378373.1	RefSeq	NP_001365302.1	4	MANE Select
ENST00000674931.1	Ensembl	ENSP00000502789.1	4	MANE Select
NM_000242.3	RefSeq	NP_000233.1	4	Standard
NM_001378374.1	RefSeq	NP_001365303.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Complement and coagulation cascades - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Staphylococcus aureus infection - Homo sapiens (human)
Regulation of toll-like receptor signaling pathway
Human Complement System

Biological Process

complement activation, lectin pathway
growth plate cartilage chondrocyte morphogenesis
proteolysis
acute-phase response
complement activation

Molecular Function

serine-type endopeptidase activity
signaling receptor binding
calcium ion binding
protein binding
mannose binding

Cellular Component

extracellular region
collagen trimer
extracellular space
cell surface
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373968
Coding exons: 4
Length: 6321
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125744
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.301	118	128	0.925	0.00000620	1591
Missense (PolyPhen)		40	42.888	0.93265		553
Synonymous	-0.0147	50	49.9	1.00	0.00000252	507
Loss of Function	0.344	4	4.81	0.831	2.01e-7	72

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-dependent lectin involved in innate immune defense. Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Binds to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells, facilitating their uptake by macrophages. May bind DNA. {ECO:0000269|PubMed:14515269}.;

Recessive Scores

pRec: 0.455

Intolerance Scores

LoFtool: 0.425
RVIS EVS: 0.42
RVIS percentile EVS: 76.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.908

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium