GeneBe

MASP2

protein-coding

MBL associated serine protease 2, the group of Sushi domain containing|Complement system activation components

Gene summary

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. [provided by RefSeq, Feb 2016]

Previous symbols:
  • MASP1P1

MANE transcript

NM_006610.4

Inheritance

AR

ClinVar variants

P:5U:141B:60

Top phenotype

MASP2 deficiency

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr1:11,022,009-11,047,239

External References & Databases

Ensembl (ENSG00000009724)NCBI Gene (10747)OMIM (605102)HGNC:6902GenCCUniProt (O00187)AlphaFoldClinVar (MASP2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~25.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency due to MASP-2 deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013423

Submitter: PanelApp Australia

immunodeficiency due to MASP-2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013423

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

MASP2 deficiencyAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Surveillance and early treatments for autoimmune phenomena may be beneficial; Infectious sequelae have been reported, but the relation to immunosuppresion regimens is unclear

Refs: 12904520; 19767106; 20338057Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MASP2 variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 157
Immunodeficiency due to MASP-2 deficiencyTotal: 65
not providedTotal: 39
MASP2-related disorderTotal: 25
Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006610.4. 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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
26
clinvar
5
clinvar
 39
missense
1
clinvar
129
clinvar
26
clinvar
3
clinvar
 159
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
2
clinvar
1
clinvar
 3
splice donor/acceptor (+/-2bp)
1
clinvar
2
clinvar
 3
Total05141528206

Highest pathogenic variant AF is 0.00000998146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006610.4RefSeqNP_006601.211MANE Select
ENST00000400897.8EnsemblENSP00000383690.311MANE Select
NM_139208.3RefSeqNP_631947.15Standard
ENST00000400898.3EnsemblENSP00000383691.35Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Complement and coagulation cascades - Homo sapiens (human)
  • Staphylococcus aureus infection - Homo sapiens (human)
  • Human Complement System
  • Dengue-2 Interactions with Complement and Coagulation Cascades
  • Complement Activation

Biological Process

  • complement activation, lectin pathway
  • proteolysis
  • complement activation
  • complement activation, classical pathway

Molecular Function

  • complement component C4b binding
  • serine-type endopeptidase activity
  • calcium ion binding
  • protein binding
  • peptidase activity

Cellular Component

  • extracellular region
  • extracellular space
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000400897
Coding exons
11
Length
20711
Individuals with no LoFs
125526
Homozygous LoFs
1
Heterozygous LoFs
221
Defined
125748
p
0.000883
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.06243953990.9910.00002254425
Missense (PolyPhen)156150.261.03821682
Synonymous-0.7121731611.070.000009931346
Loss of Function0.9322429.50.8150.00000140360

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000780.00074rare
Latino/Admixed American0.00130.0013notable
Ashkenazi Jewish0.000400.00040rare
East Asian0.00230.0023notable
Finnish0.0000960.000092rare
European (Non-Finnish)0.000720.00069rare
South Asian0.00120.0011notable
Other0.000820.00081rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase. {ECO:0000269|PubMed:10946292}.;
Disease
DISEASE: MASP2 deficiency (MASPD) [MIM:613791]: A disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease. {ECO:0000269|PubMed:12904520, ECO:0000269|PubMed:17252003}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.190

Intolerance Scores

LoFtool
0.273
RVIS EVS
0.94
RVIS percentile EVS
89.89

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.296

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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