MMP11

Chr 22

matrix metallopeptidase 11

Also known as: SL-3, ST3, STMY3

NCBI Gene: 4320ENSG00000099953UniProt: P24347

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

0
Active trials
54
Pathogenic / LP
192
ClinVar variants
46
Pubs (1 yr)
0.7
Missense Z
0.84
LOEUF
Clinical Summary— MMP11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 130 VUS of 192 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.12
OE 0.51 (0.32–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.65Z-score
OE missense 0.89 (0.81–0.99)
268 obs / 299.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.32–0.84)
0≤0.351.4
Missense OE0.89 (0.81–0.99)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 11 / 21.7Missense obs/exp: 268 / 299.7Syn Z: 1.17
DNGOF
DN
0.76top 25%
GOF
0.74top 25%
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic11
VUS130
Likely Benign5
Benign3
43
Pathogenic
11
Likely Pathogenic
130
VUS
5
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
11
0
11
VUS
0
87
43
0
130
Likely Benign
0
4
1
0
5
Benign
0
0
1
2
3
Total091992192

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

View in ClinVar →

MMP11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients