MASP2

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

Basic information

Region (hg38): 1:11022008-11047239

Previous symbols: [ "MASP1P1" ]

Links

ENSG00000009724 ∙ NCBI:10747 ∙ OMIM:605102 ∙ HGNC:6902 ∙ Uniprot:O00187 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency due to MASP-2 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
MASP2 deficiency	AR	Allergy/Immunology/Infectious	Surveillance and early treatments for autoimmune phenomena may be beneficial; Infectious sequelae have been reported, but the relation to immunosuppresion regimens is unclear	Allergy/Immunology/Infectious	12904520; 19767106; 20338057

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MASP2 gene.

• Immunodeficiency due to MASP-2 deficiency (90 variants)
• Amyotrophic lateral sclerosis type 10 (70 variants)
• not provided (51 variants)
• Inborn genetic diseases (46 variants)
• Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia (40 variants)
• TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10 (16 variants)
• Frontotemporal dementia (14 variants)
• Amyotrophic Lateral Sclerosis, Dominant (13 variants)
• not specified (6 variants)
• TARDBP-related condition (4 variants)
• Motor neuron disease (3 variants)
• FRONTOTEMPORAL DEMENTIA WITH TDP43 INCLUSIONS, TARDBP-RELATED (2 variants)
• MASP2-related condition (2 variants)
• Frontotemporal lobar degeneration, TARDBP-related (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MASP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	5	8	23
missense			58	6	9	73
nonsense		1	2			3
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)		1	2			3
splice region			2	1	1	4
non coding	7	10	84	23	6	130
Total	7	13	156	34	23

Highest pathogenic variant AF is 0.0000395

Variants in MASP2

This is a list of pathogenic ClinVar variants found in the MASP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-11022106-A-G		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Jan 06, 2022)
1-11022113-A-G		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Likely benign (May 06, 2023)
1-11022126-T-C		Amyotrophic lateral sclerosis type 10	Uncertain significance (Jan 15, 2018)
1-11022129-G-A		Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Oct 04, 2023)
1-11022183-C-G		Inborn genetic diseases • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Jan 01, 2024)
1-11022185-A-G		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Uncertain significance (Apr 11, 2023)
1-11022189-C-T		Inborn genetic diseases • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Jul 07, 2023)
1-11022196-A-G		FRONTOTEMPORAL DEMENTIA WITH TDP43 INCLUSIONS, TARDBP-RELATED	Pathogenic (Sep 15, 2009)
1-11022201-C-T		Inborn genetic diseases • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Benign/Likely benign (Dec 03, 2023)
1-11022209-A-G		Amyotrophic lateral sclerosis type 10 • TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10 • Frontotemporal lobar degeneration, TARDBP-related • TARDBP-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 01, 2024)
1-11022268-G-A		Amyotrophic lateral sclerosis type 10 • Motor neuron disease • TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Pathogenic/Likely pathogenic (Dec 11, 2023)
1-11022278-G-C		Amyotrophic lateral sclerosis type 10 • TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Uncertain significance (Mar 25, 2019)
1-11022290-G-C		Amyotrophic lateral sclerosis type 10 • Inborn genetic diseases	Uncertain significance (Feb 16, 2022)
1-11022290-G-T		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10	Pathogenic (Jan 19, 2024)
1-11022292-G-A		Amyotrophic lateral sclerosis type 10 • TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Pathogenic (Jun 26, 2023)
1-11022292-G-C		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Conflicting classifications of pathogenicity (Mar 05, 2022)
1-11022301-G-A		Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Pathogenic (Jan 17, 2023)
1-11022301-G-T			Uncertain significance (Aug 03, 2018)
1-11022302-G-T		Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Conflicting classifications of pathogenicity (Mar 06, 2023)
1-11022303-T-C			Likely benign (Oct 08, 2019)
1-11022309-A-G		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Jul 08, 2022)
1-11022318-A-G		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Likely benign (Oct 23, 2022)
1-11022320-G-A		Inborn genetic diseases	Uncertain significance (Jul 21, 2021)
1-11022334-G-A		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Uncertain significance (Jan 14, 2021)
1-11022339-G-A		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Aug 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MASP2	protein_coding	protein_coding	ENST00000400897	11	20711

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.04e-14	0.138	125526	1	221	125748	0.000883

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0624	395	399	0.991	0.0000225	4425
Missense in Polyphen		156	150.26	1.0382		1682
Synonymous	-0.712	173	161	1.07	0.00000993	1346
Loss of Function	0.932	24	29.5	0.815	0.00000140	360

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00205	0.00201
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.00229	0.00229
Finnish	0.0000964	0.0000924
European (Non-Finnish)	0.000723	0.000695
Middle Eastern	0.00229	0.00229
South Asian	0.00116	0.00111
Other	0.000819	0.000815

dbNSFP

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.
• Pathway: 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;Complement and Coagulation Cascades;lectin induced complement pathway;Innate Immune System;Immune System;Initial triggering of complement;Ficolins bind to repetitive carbohydrate structures on the target cell surface;Lectin pathway of complement activation;Creation of C4 and C2 activators;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.273
• rvis_EVS: 0.94
• rvis_percentile_EVS: 89.89

Haploinsufficiency Scores

• pHI: 0.124
• hipred: N
• hipred_score: 0.197
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.296

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Masp2
• Phenotype: immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: complement activation, lectin pathway;proteolysis;complement activation;complement activation, classical pathway
• Cellular component: extracellular region;extracellular space;extracellular exosome
• Molecular function: complement component C4b binding;serine-type endopeptidase activity;calcium ion binding;protein binding;peptidase activity;calcium-dependent protein binding