MASP1

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

Basic information

Region (hg38): 3:187217281-187291980

Previous symbols: [ "CRARF", "PRSS5" ]

Links

ENSG00000127241 ∙ NCBI:5648 ∙ OMIM:600521 ∙ HGNC:6901 ∙ Uniprot:P48740 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3MC syndrome 1 (Strong), mode of inheritance: AR
• 3MC syndrome 1 (Definitive), mode of inheritance: AR
• 3MC syndrome (Supportive), mode of inheritance: AR
• 3MC syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3MC syndrome 1	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	690758; 17937425; 18266249; 21035106; 21258343

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MASP1 gene.

• not provided (148 variants)
• 3MC syndrome 1 (86 variants)
• Inborn genetic diseases (56 variants)
• not specified (4 variants)
• Hypertrophic cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MASP1 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			1	30	6	37
missense			84	9	3	96
nonsense	1	1	2			4
start loss						0
frameshift	4	4		1		9
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			2	2	1	5
non coding				29	44	73
Total	6	6	87	69	53

Highest pathogenic variant AF is 0.00000656

Variants in MASP1

This is a list of pathogenic ClinVar variants found in the MASP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-187219780-A-G			Benign (Mar 31, 2019)
3-187220097-G-A			Likely pathogenic (Feb 22, 2017)
3-187220187-G-A			Likely benign (Sep 01, 2023)
3-187220213-A-G		Inborn genetic diseases	Uncertain significance (May 16, 2023)
3-187220228-C-A		3MC syndrome 1	Uncertain significance (Mar 29, 2024)
3-187220242-C-T			Likely benign (Dec 24, 2018)
3-187220269-A-C		MASP1-related disorder	Likely benign (Jul 20, 2020)
3-187220446-C-A			Likely benign (Jun 27, 2019)
3-187220496-C-T			Benign (Sep 19, 2019)
3-187220496-C-CT			Benign (Aug 21, 2019)
3-187220496-C-CTTT			Likely benign (Nov 02, 2019)
3-187220499-T-TC			Likely benign (Nov 14, 2019)
3-187220847-C-G			Benign (Mar 19, 2019)
3-187220911-C-G			Benign (Dec 12, 2018)
3-187220928-C-T			Likely benign (Nov 02, 2020)
3-187220985-C-A			Likely benign (May 13, 2021)
3-187221030-C-T		MASP1-related disorder	Benign/Likely benign (Apr 17, 2022)
3-187221033-A-T		MASP1-related disorder	Uncertain significance (Dec 15, 2023)
3-187221104-A-G		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
3-187221124-G-A		Inborn genetic diseases	Uncertain significance (Aug 24, 2022)
3-187221168-C-T			Benign (Oct 16, 2018)
3-187221403-T-A			Benign (Oct 16, 2018)
3-187223009-G-T			Benign (Apr 16, 2019)
3-187223123-T-C		3MC syndrome 1	Uncertain significance (Apr 21, 2020)
3-187223126-C-T		3MC syndrome 1	Likely pathogenic (Nov 14, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MASP1	protein_coding	protein_coding	ENST00000296280	11	73869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.23e-11	0.757	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.160	401	392	1.02	0.0000232	4779
Missense in Polyphen		100	121.23	0.8249		1454
Synonymous	-1.55	186	161	1.16	0.0000100	1409
Loss of Function	1.66	22	32.1	0.685	0.00000179	382

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000470	0.000470
Ashkenazi Jewish	0.000893	0.000893
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000202	0.000202
Middle Eastern	0.0000544	0.0000544
South Asian	0.000327	0.000327
Other	0.000326	0.000326

dbNSFP

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.
• 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;Vesicle-mediated transport;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;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.127
• rvis_EVS: -0.63
• rvis_percentile_EVS: 16.81

Haploinsufficiency Scores

• pHI: 0.299
• hipred: Y
• hipred_score: 0.584
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.693

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Masp1
• Phenotype: growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Zebrafish Information Network

• Gene name: masp1
• Affected structure: neural crest cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: complement activation, lectin pathway;proteolysis;receptor-mediated endocytosis;complement activation
• Cellular component: extracellular region;extracellular space;nucleoplasm;cytosol
• Molecular function: serine-type endopeptidase activity;calcium ion binding;protein binding;peptidase activity;protein homodimerization activity;calcium-dependent protein binding