MASP1

Chr 3AR

MBL associated serine protease 1

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

NCBI Gene: 5648 ENSG00000127241 UniProt: P48740 OMIM: 600521

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.981 OMIM phenotype

Clinical Summary— MASP1

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Gene-Disease Validity (ClinGen)

3MC syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

26 unique Pathogenic / Likely Pathogenic· 193 VUS of 406 total submissions

Explore recent and relevant literature in Research Assistant →

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMASP1-related 3MC syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6453th %ile

GOF

0.7027th %ile

LOF

0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

406 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic11

VUS193

Likely Benign106

Benign58

Conflicting17

Pathogenic

Likely Pathogenic

193

VUS

106

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	4	1	0	15
Likely Pathogenic	8	3	0	0	11
VUS	3	188	2	0	193
Likely Benign	0	13	43	50	106
Benign	0	4	46	8	58
Conflicting	—				17
Total	21	212	92	58	400

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

41 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap MASP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →