MMP19
protein-codingmatrix metallopeptidase 19, the group of M10 matrix metallopeptidases
Gene summary
This gene encodes a member of a family of proteins that 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. The encoded protein is secreted as an inactive proprotein, which is activated upon cleavage by extracellular proteases. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]
- MMP18
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0012687
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0012687
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MMP19 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002429.6. 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 | 8 | 1 | 11 | ||
| missense | 69 | 12 | 2 | 83 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 72 | 22 | 3 | 97 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002420.1 | 9 | MANE Select | |
| Ensembl | ENSP00000313437.4 | 9 | MANE Select | |
| RefSeq | NP_001259030.1 | 6 | Standard | |
| RefSeq | NP_001401304.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Matrix Metalloproteinases
- Extracellular matrix organization
- Degradation of the extracellular matrix
Biological Process
- angiogenesis
- ovarian follicle development
- ovulation from ovarian follicle
- luteolysis
- proteolysis
Molecular Function
- metalloendopeptidase activity
- serine-type endopeptidase activity
- zinc ion binding
Cellular Component
- extracellular region
- extracellular space
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000322569
- Coding exons
- 9
- Length
- 7534
- Individuals with no LoFs
- 125411
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 337
- Defined
- 125748
- p
- 0.00134
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.363 | 284 | 302 | 0.941 | 0.0000173 | 3268 |
| Missense (PolyPhen) | 122 | 124.28 | 0.98164 | 1366 | ||
| Synonymous | 0.235 | 115 | 118 | 0.973 | 0.00000670 | 1024 |
| Loss of Function | -0.366 | 29 | 27.0 | 1.08 | 0.00000156 | 257 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.0012 | 0.0011 | notable |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.0025 | 0.0024 | notable |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.0018 | 0.0018 | notable |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis. Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin. {ECO:0000269|PubMed:10809722, ECO:0000269|PubMed:10922468}.;
- Disease
- DISEASE: Cavitary optic disc anomalies (CODA) [MIM:611543]: An ocular disease characterized by a profound excavation of the optic nerve. Clinical phenotype is variable and includes congenitally excavated optic nerves as well as other features of optic pit, optic nerve coloboma, and morning glory disk anomaly. Patients with CODA have a strong predilection for retinal detachment and/or separation of the retinal layers (retinoschisis) that lead to profound central vision loss. {ECO:0000269|PubMed:25581579}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.146
Intolerance Scores
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 44.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.206
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |