MMP25
protein-codingmatrix metallopeptidase 25, 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 MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily, attached to the plasma membrane via a glycosylphosphatidyl inositol anchor. In response to bacterial infection or inflammation, the encoded protein is thought to inactivate alpha-1 proteinase inhibitor, a major tissue protectant against proteolytic enzymes released by activated neutrophils, facilitating the transendothelial migration of neutrophils to inflammatory sites. The encoded protein may also play a role in tumor invasion and metastasis through activation of MMP2. The gene has previously been referred to as MMP20 but has been renamed MMP25. [provided by RefSeq, Jul 2008]
- MMPL1
- MMP20
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.7 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 MMP25 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022468.5. 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 | 0 | |||||
| missense | 135 | 2 | 137 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 139 | 2 | 0 | 141 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071913.1 | 10 | MANE Select | |
| Ensembl | ENSP00000337816.4 | 10 | MANE Select | |
| Ensembl | ENSP00000482854.2 | 5 | Standard | |
| Ensembl | ENSP00000520889.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mmp25b | Danio rerio | Structure: trigeminal sensory neuron Quality: decreased process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Matrix Metalloproteinases
- Neutrophil degranulation
- Extracellular matrix organization
- Innate Immune System
- Immune System
Biological Process
- proteolysis
- inflammatory response
- extracellular matrix organization
- collagen catabolic process
- neutrophil degranulation
Molecular Function
- metalloendopeptidase activity
- zinc ion binding
Cellular Component
- extracellular space
- plasma membrane
- membrane
- integral component of membrane
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336577
- Coding exons
- 10
- Length
- 14046
- Individuals with no LoFs
- 125601
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 146
- Defined
- 125748
- p
- 0.000585
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.879 | 387 | 341 | 1.13 | 0.0000199 | 3534 |
| Missense (PolyPhen) | 159 | 143.56 | 1.1075 | 1490 | ||
| Synonymous | -1.97 | 183 | 152 | 1.20 | 0.00000929 | 1198 |
| Loss of Function | 0.595 | 22 | 25.2 | 0.872 | 0.00000137 | 238 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00061 | 0.00055 | rare |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00083 | 0.00076 | rare |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.00076 | 0.00073 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May activate progelatinase A.;
Recessive Scores
- pRec
- 0.310
Intolerance Scores
- LoFtool
- 0.859
- RVIS EVS
- -0.22
- RVIS percentile EVS
- 37.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.392
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |