MASP1

Chr 3

MBL associated serine protease 1

Also known as: 3MC1, CRARF, CRARF1, MAP-1, MAP1, MASP, MASP-3, MASP3

NCBI Gene: 5648 ENSG00000127241 UniProt: P48740

This gene encodes a serine protease that activates the lectin pathway of complement activation and may also function in coagulation by cleaving fibrinogen and factor XIII. Mutations cause 3MC syndrome 1, an autosomal recessive disorder characterized by multiple congenital anomalies affecting craniofacial development, skeletal system, and other organ systems. The gene shows very low constraint to loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProt3MC syndrome 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · 3MC syndrome 1 · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.98

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.66

OE 0.68 (0.49–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.16Z-score

OE missense 1.02 (0.94–1.11)

401 obs / 392.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.68 (0.49–0.98)

0≤0.351.4

Missense OE?1.02 (0.94–1.11)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 22 / 32.1Missense obs/exp: 401 / 392.1Syn Z: -1.55

Background carrier burden — how many people carry a rare variant somewhere in MASP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,364 rare PASS variants

Rare truncating (LoF)

1 in 520

210 rare PASS variants

Rare synonymous (reference)

1 in 71

552 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MASP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 50	1 in 570
South Asian	~43k	1 in 40	1 in 410
Remaining (unassigned)	~30k	1 in 35	1 in 370
European (Finnish)	~27k	1 in 150	1 in 1,800
Admixed American	~22k	1 in 40	1 in 340
African / African American	~21k	1 in 35	1 in 590
East Asian	~20k	1 in 41	1 in 1,800
Ashkenazi Jewish	~13k	1 in 120	1 in 530
Middle Eastern	~2,884	1 in 39	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓