MMP2

Chr 16AR

matrix metallopeptidase 2

Also known as: CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1

This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

Multicentric osteolysis, nodulosis, and arthropathyMIM #259600
AR
7
Active trials
27
Pathogenic / LP
280
ClinVar variants
6
Pubs (1 yr)
0.7
Missense Z
0.36
LOEUF
Clinical SummaryMMP2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 113 VUS of 280 total submissions
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — MMP2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.36LOEUF
pLI 0.839
Z-score 4.30
OE 0.19 (0.100.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.71Z-score
OE missense 0.90 (0.820.98)
351 obs / 390.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.100.36)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.820.98)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
01.21.6
LoF obs/exp: 6 / 32.4Missense obs/exp: 351 / 390.5Syn Z: -1.27

ClinVar Variant Classifications

280 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic7
VUS113
Likely Benign88
Benign44
Conflicting8
20
Pathogenic
7
Likely Pathogenic
113
VUS
88
Likely Benign
44
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
16
0
20
Likely Pathogenic
1
1
5
0
7
VUS
2
92
18
1
113
Likely Benign
0
0
36
52
88
Benign
0
2
41
1
44
Conflicting
8
Total69611654280

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

View in ClinVar →

Protein Context — Lollipop Plot

MMP2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MMP2-related Winchester syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Aortic Aneurysm and Dissection

MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta

ACTIVE NOT RECRUITING
NCT05434481Phase NAUniversity Hospital, AngersStarted 2022-09-07
Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases
Knee Osteoarthritis

Dietary Supplementation With Blueberry in OA

ACTIVE NOT RECRUITING
NCT05784545Phase NAUniversity of ExeterStarted 2023-05-22
Blueberry powder supplementMaltodextrin supplementation
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet
Recurrent GlioblastomaRecurrent Malignant GliomaRecurrent WHO Grade II Glioma

Chimeric Antigen Receptor (CAR) T Cells With a Chlorotoxin Tumor-Targeting Domain for the Treatment of MMP2+ Recurrent or Progressive Glioblastoma

ACTIVE NOT RECRUITING
NCT04214392Phase PHASE1City of Hope Medical CenterStarted 2020-02-26
Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT delivery)Chlorotoxin (EQ)-CD28-CD3zeta-CD19t-expressing CAR T-lymphocytes (via ICT/ICV dual delivery)
Pelvic Organ ProlapseFemale Urogenital Diseases

Pelvic Organs Prolapse Treatment Using Neodymium Laser

ACTIVE NOT RECRUITING
NCT05000957Phase NAMeLSyTech, LtdStarted 2021-10-03
Laser TreatmentBlood analysisСlinical urine test
Heart Failure

The Impact of Genetic Polymorphism on the Echocardiographic Parameters and Cardiac Fibrosis Markers in Response to Empagliflozin Treatment Among Patients With Heart Failure

ACTIVE NOT RECRUITING
NCT06503601Ain Shams UniversityStarted 2023-07-30
COL4A1\2COL4A1-Related Brain Small Vessel Disease With Haemorrhage

COL4A1COL4A2: Study of Pathological Conditions Involving Multiple Organs Caused by Mutations in the COL4A1 and COL4A2 Genes

RECRUITING
NCT07374913Phase NAMeyer Children's Hospital IRCCSStarted 2021-05-01
Ophtalmological and cardiological screening
Clinical Literature
Landmark / reviewRecent case evidence