MMP8
protein-codingmatrix metallopeptidase 8, the group of M10 matrix metallopeptidases
Gene summary
This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
- CLG1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.3 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 MMP8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002424.3. 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 | 2 | 3 | 5 | |||
| missense | 66 | 7 | 3 | 76 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 66 | 9 | 6 | 81 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002415.1 | 10 | MANE Select | |
| Ensembl | ENSP00000236826.3 | 10 | MANE Select | |
| RefSeq | NP_001291370.1 | 10 | Standard | |
| RefSeq | NP_001291371.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Matrix Metalloproteinases
- Neutrophil degranulation
- Collagen degradation
- Extracellular matrix organization
- Innate Immune System
Biological Process
- proteolysis
- positive regulation of gene expression
- negative regulation of gene expression
- extracellular matrix disassembly
- extracellular matrix organization
Molecular Function
- endopeptidase activity
- metalloendopeptidase activity
- serine-type endopeptidase activity
- zinc ion binding
Cellular Component
- extracellular region
- extracellular space
- specific granule lumen
- collagen-containing extracellular matrix
- tertiary granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000236826
- Coding exons
- 10
- Length
- 15256
- Individuals with no LoFs
- 125459
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 286
- Defined
- 125746
- p
- 0.00114
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.613 | 277 | 250 | 1.11 | 0.0000123 | 3086 |
| Missense (PolyPhen) | 116 | 102.38 | 1.1331 | 1268 | ||
| Synonymous | -1.70 | 110 | 89.5 | 1.23 | 0.00000477 | 857 |
| Loss of Function | -1.49 | 32 | 24.1 | 1.33 | 0.00000127 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0028 | 0.0026 | notable |
| Latino/Admixed American | 0.0013 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.0014 | 0.0013 | notable |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.0022 | 0.0021 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Can degrade fibrillar type I, II, and III collagens.;
Recessive Scores
- pRec
- 0.283
Intolerance Scores
- LoFtool
- 0.938
- RVIS EVS
- 1.58
- RVIS percentile EVS
- 95.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.630
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |