GeneBe

MASP1

protein-coding

MBL associated serine protease 1, the group of Serine proteases|Complement system activation components|Sushi domain containing

Gene summary

This gene encodes a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays an essential role in the innate and adaptive immune response. The encoded protein is synthesized as a zymogen and is activated when it complexes with the pathogen recognition molecules of lectin pathway, the mannose-binding lectin and the ficolins. This protein is not directly involved in complement activation but may play a role as an amplifier of complement activation by cleaving complement C2 or by activating another complement serine protease, MASP-2. The encoded protein is also able to cleave fibrinogen and factor XIII and may may be involved in coagulation. A splice variant of this gene which lacks the serine protease domain functions as an inhibitor of the complement pathway. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

Previous symbols:
  • CRARF
  • PRSS5

MANE transcript

NM_139125.4

Inheritance

AR

ClinVar variants

P:28U:148B:83

Top phenotype

3MC syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr3:187,217,282-187,291,980

External References & Databases

Ensembl (ENSG00000127241)NCBI Gene (5648)OMIM (600521)HGNC:6901GenCCUniProt (P48740)AlphaFoldClinVar (MASP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~74.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

3MC syndrome 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009770

Submitter: ClinGen

MASP1 was first reported in relation to autosomal recessive 3MC syndrome in 2010 (Sirmaci et al., PMID: 21035106). 3MC syndrome encompasses four rare disorders that were previously referred to as the Mingarelli, Malpuech, Michels, and Carnevale syndromes. The main features of these syndromes are facial dysmorphisms that include hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistently seen in patients with these syndromes. 13 variants (missense, nonsense, and splice site) that have been reported in 17 probands in 4 publications (PMIDs: 21035106, 21258343, 26419238, 26789649) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by an animal model that recapitulated phenotypes seen in humans with 3MC syndrome, and a protein interaction study describing the interaction between MASP1 and COLEC11 (PMIDs: 21258343, 21258343). In summary, there is definitive evidence supporting the relationship between MASP1 and autosomal recessive 3MC syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations GCEP on the meeting date January 15, 2026 (SOP Version 11).

3MC syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009770

Submitter: PanelApp Australia

3MC syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017398

Submitter: Orphanet

3MC syndrome 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009770

Submitter: G2P

3MC syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009770

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

3MC syndrome 1AR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 690758; 17937425; 18266249; 21035106; 21258343Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MASP1 variants in ClinVar

9 Conditions Cataloged
3MC syndrome 1Total: 117
Inborn genetic diseasesTotal: 112
not providedTotal: 107
not specifiedTotal: 58
MASP1-related disorderTotal: 29
MASP1-related disordersTotal: 4
Monogenic hearing lossTotal: 2
Hypertrophic cardiomyopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139125.4. 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
1
clinvar
62
clinvar
3
clinvar
 66
missense
3
clinvar
5
clinvar
144
clinvar
17
clinvar
1
clinvar
 170
nonsense
4
clinvar
5
clinvar
2
clinvar
 11
start loss
0
frameshift
4
clinvar
6
clinvar
 10
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total1117148794259

Highest pathogenic variant AF is 0.0002490552

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_139125.4RefSeqNP_624302.111MANE Select
ENST00000296280.11EnsemblENSP00000296280.711MANE Select
NM_001031849.3RefSeqNP_001027019.19Standard
NM_001879.6RefSeqNP_001870.316MANE Plus Clinical

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
masp1Danio rerio

Structure: neural crest cell

Quality: mislocalised

abnormal

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
  • receptor-mediated endocytosis
  • complement activation

Molecular Function

  • serine-type endopeptidase activity
  • calcium ion binding
  • protein binding
  • peptidase activity
  • protein homodimerization activity

Cellular Component

  • extracellular region
  • extracellular space
  • nucleoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000296280
Coding exons
11
Length
73869
Individuals with no LoFs
125689
Homozygous LoFs
0
Heterozygous LoFs
59
Defined
125748
p
0.000235
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.1604013921.020.00002324779
Missense (PolyPhen)100121.230.82491454
Synonymous-1.551861611.160.00001001409
Loss of Function1.662232.10.6850.00000179382

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.000350.00035rare
Ashkenazi Jewish0.000890.00089rare
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.000200.00020rare
South Asian0.000330.00033rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5. Also plays a role in development (PubMed:21258343). {ECO:0000269|PubMed:11485744, ECO:0000269|PubMed:21258343}.;
Disease
DISEASE: 3MC syndrome 1 (3MC1) [MIM:257920]: A form of 3MC syndrome, an autosomal recessive disorder characterized by facial dysmorphism, craniosynostosis, learning disability, and genital, limb and vesicorenal anomalies. Facial features include hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes. {ECO:0000269|PubMed:21258343, ECO:0000269|PubMed:26419238, ECO:0000269|PubMed:28301481}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.173

Intolerance Scores

LoFtool
0.127
RVIS EVS
-0.63
RVIS percentile EVS
16.81

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.693

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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