MMP3
protein-codingmatrix metallopeptidase 3, the group of M10 matrix metallopeptidases
Gene summary
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. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]
- STMY1
- STMY
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MMP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002422.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 6 | 10 | |||
| missense | 67 | 6 | 73 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 0 | 0 | 69 | 10 | 7 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002413.1 | 10 | MANE Select | |
| Ensembl | ENSP00000299855.5 | 10 | MANE Select | |
| Ensembl | ENSP00000398346.1 | 3 | Standard | |
| Ensembl | ENSP00000435255.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TNF signaling pathway - Homo sapiens (human)
- Prostate cancer - Homo sapiens (human)
- IL-17 signaling pathway - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Rheumatoid arthritis - Homo sapiens (human)
Biological Process
- proteolysis
- negative regulation of hydrogen peroxide metabolic process
- cytokine-mediated signaling pathway
- extracellular matrix disassembly
- extracellular matrix organization
Molecular Function
- endopeptidase activity
- metalloendopeptidase activity
- serine-type endopeptidase activity
- protein binding
- metallopeptidase activity
Cellular Component
- extracellular region
- extracellular space
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299855
- Coding exons
- 10
- Length
- 8003
- Individuals with no LoFs
- 125591
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 155
- Defined
- 125746
- p
- 0.000617
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.644 | 285 | 256 | 1.11 | 0.0000128 | 3136 |
| Missense (PolyPhen) | 94 | 80.177 | 1.1724 | 1004 | ||
| Synonymous | -1.38 | 114 | 96.8 | 1.18 | 0.00000515 | 920 |
| Loss of Function | 0.0341 | 22 | 22.2 | 0.992 | 0.00000112 | 275 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0013 | notable |
| Latino/Admixed American | 0.00090 | 0.00090 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00093 | 0.00092 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.0012 | 0.0011 | notable |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.;
- Disease
- DISEASE: Coronary heart disease 6 (CHDS6) [MIM:614466]: A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. {ECO:0000269|PubMed:12477941, ECO:0000269|PubMed:8662692}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.;
Recessive Scores
- pRec
- 0.866
Intolerance Scores
- LoFtool
- 0.898
- RVIS EVS
- -0.66
- RVIS percentile EVS
- 15.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.589
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |