MMP2
matrix metallopeptidase 2, the group of M10 matrix metallopeptidases
Basic information
Region (hg38): 16:55389699-55506691
Previous symbols: [ "CLG4", "CLG4A" ]
Links
Phenotypes
GenCC
Source:
- multicentric osteolysis, nodulosis, and arthropathy (Strong), mode of inheritance: AR
- multicentric osteolysis, nodulosis, and arthropathy (Strong), mode of inheritance: AR
- multicentric osteolysis-nodulosis-arthropathy spectrum (Supportive), mode of inheritance: AR
- Winchester syndrome (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Multicentric osteolysis, nodulosis, and arthropathy (Torg-Winchester syndrome) | AR | General | 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 | Dermatologic; Musculoskeletal | 5795345; 2625626; 9843039; 10861676; 10861675; 11431697; 15691365; 16542393; 17059372; 20720557; 20865259; 22876575 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (228 variants)
- Multicentric osteolysis nodulosis arthropathy spectrum (106 variants)
- Inborn genetic diseases (31 variants)
- not specified (5 variants)
- Multicentric osteolysis, nodulosis, and arthropathy (3 variants)
- Multicentric Osteolysis-Nodulosis-Arthropathy (MONA) Spectrum Disorders (2 variants)
- MMP2-related condition (1 variants)
- Lip and oral cavity carcinoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMP2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 52 | 65 | ||||
| missense | 91 | 98 | ||||
| nonsense | 7 | |||||
| start loss | 1 | |||||
| frameshift | 5 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| splice region ? | 2 | 4 | 1 | 7 | ||
| non coding ? | 29 | 21 | 50 | 100 | ||
| Total | 10 | 5 | 127 | 75 | 63 |
Highest pathogenic variant AF is 0.00000658
Variants in MMP2
This is a list of pathogenic ClinVar variants found in the MMP2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MMP2 | protein_coding | protein_coding | ENST00000219070 | 13 | 116992 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.839 | 0.161 | 125726 | 0 | 22 | 125748 | 0.0000875 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.710 | 351 | 390 | 0.899 | 0.0000246 | 4364 |
| Missense in Polyphen | 146 | 173.35 | 0.84223 | 1850 | ||
| Synonymous | -1.27 | 178 | 158 | 1.13 | 0.0000106 | 1242 |
| Loss of Function | 4.30 | 6 | 32.4 | 0.185 | 0.00000168 | 364 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.000168 | 0.000163 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.0000530 | 0.0000527 |
| Middle Eastern | 0.000168 | 0.000163 |
| South Asian | 0.000229 | 0.000229 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; FUNCTION: Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro- inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.;
- Disease
- DISEASE: Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600]: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. {ECO:0000269|PubMed:11431697, ECO:0000269|PubMed:15691365, ECO:0000269|PubMed:16542393}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Relaxin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Bladder cancer - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Matrix Metalloproteinases;Angiogenesis overview;AGE-RAGE pathway;MAPK6-MAPK4 signaling;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NF-kB survival signaling;Lung fibrosis;VEGFA-VEGFR2 Signaling Pathway;Protein alkylation leading to liver fibrosis;Interleukin-4 and 13 signaling;EMT transition in Colorectal Cancer;Signal Transduction;inhibition of matrix metalloproteinases;MAPK6/MAPK4 signaling;Collagen degradation;Metabolism of proteins;Extracellular matrix organization;ATF-2 transcription factor network;Activation of Matrix Metalloproteinases;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);MAPK family signaling cascades;Degradation of the extracellular matrix;Angiopoietin receptor Tie2-mediated signaling;Direct p53 effectors;Osteopontin-mediated events;Regulation of nuclear beta catenin signaling and target gene transcription;LPA receptor mediated events;amb2 Integrin signaling;Plasma membrane estrogen receptor signaling;FOXM1 transcription factor network;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Syndecan-2-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.962
Intolerance Scores
- loftool
- 0.202
- rvis_EVS
- -0.06
- rvis_percentile_EVS
- 48.84
Haploinsufficiency Scores
- pHI
- 0.878
- hipred
- Y
- hipred_score
- 0.749
- ghis
- 0.562
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.725
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mmp2
- Phenotype
- growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; neoplasm; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; respiratory system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype;
Zebrafish Information Network
- Gene name
- mmp2
- Affected structure
- interrenal angiogenic sprout
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- angiogenesis;response to hypoxia;blood vessel maturation;intramembranous ossification;proteolysis;embryo implantation;cytokine-mediated signaling pathway;extracellular matrix disassembly;extracellular matrix organization;collagen catabolic process;endodermal cell differentiation;cellular protein metabolic process;ephrin receptor signaling pathway;tissue remodeling;face morphogenesis;bone trabecula formation;cellular response to amino acid stimulus;positive regulation of vascular smooth muscle cell proliferation
- Cellular component
- extracellular region;extracellular space;nucleus;mitochondrion;plasma membrane;sarcomere;collagen-containing extracellular matrix
- Molecular function
- metalloendopeptidase activity;serine-type endopeptidase activity;protein binding;metallopeptidase activity;zinc ion binding