MASP2

Chr 1AR

MBL associated serine protease 2

Also known as: MAP-2, MAP19, MASP-2, MASP1P1, sMAP

NCBI Gene: 10747 ENSG00000009724 UniProt: O00187 OMIM: 605102

This serine protease activates the lectin pathway of the complement system by cleaving complement components C2 and C4 to generate C3 convertase, and also participates in coagulation by converting prothrombin to thrombin. Autosomal recessive mutations cause MASP2 deficiency, which results in immune system dysfunction due to impaired complement activation. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 1.151 OMIM phenotype

Clinical Summary— MASP2

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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

4 unique Pathogenic / Likely Pathogenic· 145 VUS of 215 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 0.93

OE 0.81 (0.59–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.99 (0.91–1.08)

395 obs / 398.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.81 (0.59–1.15)

0≤0.351.4

Missense OE?0.99 (0.91–1.08)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 24 / 29.5Missense obs/exp: 395 / 398.5Syn Z: -0.71

This gene — mechanism propensity

0.6066th %ile

GOF

0.6541th %ile

LOF

0.3745th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

215 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic4

VUS145

Likely Benign31

Benign14

Conflicting13

Likely Pathogenic

145

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	2	2	0	0	4
VUS	2	123	13	7	145
Likely Benign	0	16	4	11	31
Benign	0	4	1	9	14
Conflicting	—				13
Total	4	145	18	27	207

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap MASP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →