MMP9

matrix metallopeptidase 9, the group of M10 matrix metallopeptidases

Basic information

Region (hg38): 20:46008908-46016561

Previous symbols: [ "CLG4B" ]

Links

ENSG00000100985 ∙ NCBI:4318 ∙ OMIM:120361 ∙ HGNC:7176 ∙ Uniprot:P14780 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• metaphyseal anadysplasia (Supportive), mode of inheritance: AD
• metaphyseal anadysplasia 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Metaphyseal anadysplasia 2	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	Musculoskeletal	4252978; 1867263; 19615667

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MMP9 gene.

• Metaphyseal anadysplasia 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMP9 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			2	68	5	75
missense		1	173	5	4	183
nonsense	1		4			5
start loss			1			1
frameshift		1	3	1		5
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)			4			4
splice region			8	6	3	17
non coding			5	31	16	52
Total	1	2	194	106	25

Variants in MMP9

This is a list of pathogenic ClinVar variants found in the MMP9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-46008928-T-A		Metaphyseal anadysplasia 2	Uncertain significance (Jan 18, 2024)
20-46008939-C-A		not specified	Uncertain significance (Apr 29, 2024)
20-46008941-G-A			Likely benign (Oct 23, 2018)
20-46008953-G-T			Likely benign (Oct 05, 2023)
20-46008954-G-A			Uncertain significance (Nov 16, 2022)
20-46008965-G-T			Likely benign (Apr 15, 2022)
20-46008971-C-A			Likely benign (Aug 16, 2022)
20-46008971-C-T		Metaphyseal anadysplasia 2	Benign/Likely benign (Jan 25, 2024)
20-46008974-C-T			Likely benign (Dec 22, 2023)
20-46008984-G-A		Metaphyseal anadysplasia 2	Uncertain significance (Jan 12, 2018)
20-46008985-C-T		Metaphyseal anadysplasia 2	Benign/Likely benign (Jan 29, 2024)
20-46008996-C-T		Metaphyseal anadysplasia 2 • MMP9-related disorder	Benign/Likely benign (Jan 14, 2024)
20-46008997-G-A			Uncertain significance (Jun 11, 2023)
20-46009001-G-A			Likely benign (Aug 19, 2022)
20-46009006-C-T		Metaphyseal anadysplasia 2	Uncertain significance (Nov 28, 2022)
20-46009007-C-T		Metaphyseal anadysplasia 2	Conflicting classifications of pathogenicity (Jul 23, 2022)
20-46009013-G-T			Likely benign (May 27, 2022)
20-46009019-C-T			Likely benign (Aug 01, 2022)
20-46009020-C-T		not specified	Uncertain significance (Mar 07, 2024)
20-46009035-A-G			Uncertain significance (Apr 20, 2020)
20-46009039-A-G		Metaphyseal anadysplasia 2	Benign (Feb 01, 2024)
20-46009046-C-T			Likely benign (Mar 15, 2021)
20-46009047-G-A		not specified	Uncertain significance (Jan 17, 2024)
20-46009055-G-T			Uncertain significance (May 07, 2024)
20-46009713-A-G			Likely benign (Mar 06, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MMP9	protein_coding	protein_coding	ENST00000372330	13	7654

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.89e-17	0.0256	125514	2	232	125748	0.000931

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.415	416	441	0.944	0.0000290	4518
Missense in Polyphen		144	147.63	0.97539		1572
Synonymous	0.147	196	199	0.987	0.0000152	1452
Loss of Function	0.631	28	31.8	0.879	0.00000148	344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000681	0.000680
Ashkenazi Jewish	0.0101	0.0101
East Asian	0.000762	0.000761
Finnish	0.00	0.00
European (Non-Finnish)	0.000740	0.000721
Middle Eastern	0.000762	0.000761
South Asian	0.000458	0.000457
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide. {ECO:0000269|PubMed:1480034}.
• Disease: DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. {ECO:0000269|PubMed:18455130}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Metaphyseal anadysplasia 2 (MANDP2) [MIM:613073]: A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia. {ECO:0000269|PubMed:19615667}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);Bladder cancer - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Matrix Metalloproteinases;Osteopontin Signaling;Angiogenesis;Angiogenesis overview;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;AGE-RAGE pathway;Spinal Cord Injury;Mammary gland development pathway - Involution (Stage 4 of 4);IL1 and megakaryocytes in obesity;Photodynamic therapy-induced NF-kB survival signaling;Lung fibrosis;Interleukin-4 and 13 signaling;EMT transition in Colorectal Cancer;Endochondral Ossification;Neutrophil degranulation;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;inhibition of matrix metalloproteinases;Collagen degradation;Collagen formation;Extracellular matrix organization;Innate Immune System;Immune System;Activation of Matrix Metalloproteinases;CXCR4-mediated signaling events;Degradation of the extracellular matrix;Signaling by SCF-KIT;Signaling by Receptor Tyrosine Kinases;Osteopontin-mediated events;Regulation of nuclear beta catenin signaling and target gene transcription;LPA receptor mediated events;Validated targets of C-MYC transcriptional activation;AP-1 transcription factor network;Syndecan-1-mediated signaling events;amb2 Integrin signaling;Plasma membrane estrogen receptor signaling;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Syndecan-4-mediated signaling events;FGF signaling pathway (Consensus)

Recessive Scores

• pRec: 0.972

Intolerance Scores

• loftool: 0.926
• rvis_EVS: 0.67
• rvis_percentile_EVS: 84.68

Haploinsufficiency Scores

• pHI: 0.240
• hipred: N
• hipred_score: 0.382
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.556

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Mmp9
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); neoplasm; 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; 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype

Zebrafish Information Network

• Gene name: mmp9
• Affected structure: mandibular arch skeleton
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: skeletal system development;ossification;positive regulation of protein phosphorylation;proteolysis;embryo implantation;cytokine-mediated signaling pathway;extracellular matrix disassembly;extracellular matrix organization;macrophage differentiation;positive regulation of cell migration;collagen catabolic process;cellular response to reactive oxygen species;endodermal cell differentiation;negative regulation of apoptotic process;neutrophil degranulation;positive regulation of DNA binding;positive regulation of epidermal growth factor receptor signaling pathway;ephrin receptor signaling pathway;leukocyte migration;positive regulation of keratinocyte migration;cellular response to cadmium ion;positive regulation of release of cytochrome c from mitochondria;regulation of neuroinflammatory response;positive regulation of receptor binding;positive regulation of vascular smooth muscle cell proliferation;negative regulation of intrinsic apoptotic signaling pathway;negative regulation of cation channel activity;negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
• Cellular component: extracellular region;extracellular space;collagen-containing extracellular matrix;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: endopeptidase activity;metalloendopeptidase activity;serine-type endopeptidase activity;protein binding;collagen binding;metallopeptidase activity;zinc ion binding;identical protein binding