MMP2

matrix metallopeptidase 2, the group of M10 matrix metallopeptidases

Basic information

Region (hg38): 16:55389700-55506691

Previous symbols: [ "CLG4", "CLG4A" ]

Links

ENSG00000087245

∙ NCBI:4313 ∙ OMIM:120360 ∙ HGNC:7166 ∙ Uniprot:P08253 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the MMP2 gene.

not_provided (231 variants)
Inborn_genetic_diseases (80 variants)
Multicentric_osteolysis_nodulosis_arthropathy_spectrum (63 variants)
Multicentric_osteolysis,_nodulosis,_and_arthropathy (17 variants)
MMP2-related_disorder (8 variants)
not_specified (3 variants)
Intellectual_disability (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. These statistics are base on transcript: NM_000004530.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	83 clinvar	4 clinvar	89
missense	2 clinvar	4 clinvar	142 clinvar	6 clinvar	4 clinvar	158
nonsense	9 clinvar	2 clinvar	1 clinvar			12
start loss			1			1
frameshift	7 clinvar	2 clinvar	2 clinvar			11
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	18	11	149	89	8

Highest pathogenic variant AF is 0.000055757868

Loading clinvar variants...

GnomAD

Source: gnomAD

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: dbNSFP

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