MMP14

matrix metallopeptidase 14, the group of M10 matrix metallopeptidases

Basic information

Region (hg38): 14:22836559-22849041

Links

ENSG00000157227 ∙ NCBI:4323 ∙ OMIM:600754 ∙ HGNC:7160 ∙ Uniprot:P50281 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Winchester syndrome (Limited), mode of inheritance: AR
• Winchester syndrome (Moderate), mode of inheritance: AR
• multicentric osteolysis-nodulosis-arthropathy spectrum (Supportive), mode of inheritance: AR
• Winchester syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
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	Biochemical; Craniofacial; Musculoskeletal	4238825; 22922033

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MMP14 gene.

• not provided (188 variants)
• Inborn genetic diseases (28 variants)
• Winchester syndrome (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMP14 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				40	8	48
missense			101	3	6	110
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			2	6		8
non coding			1	14	22	37
Total	0	0	109	57	36

Variants in MMP14

This is a list of pathogenic ClinVar variants found in the MMP14 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-22836774-G-C			Benign (May 13, 2021)
14-22836827-G-A			Benign (Jan 18, 2024)
14-22836833-A-AG			Uncertain significance (Jul 18, 2022)
14-22836839-C-T		MMP14-related disorder	Benign (Jan 31, 2024)
14-22836842-C-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
14-22836843-G-A			Uncertain significance (Mar 13, 2022)
14-22836853-G-C			Likely benign (Dec 14, 2023)
14-22836867-C-G		Winchester syndrome	Pathogenic (Sep 07, 2012)
14-22836878-G-A			Uncertain significance (Jan 07, 2024)
14-22836879-C-T			Uncertain significance (Jul 09, 2023)
14-22836890-C-T		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)
14-22836893-G-A			Uncertain significance (Mar 26, 2022)
14-22836894-G-T		Inborn genetic diseases	Uncertain significance (Jan 20, 2023)
14-22836898-G-C			Likely benign (Jun 20, 2023)
14-22836908-A-T			Uncertain significance (Aug 19, 2021)
14-22836910-C-T			Likely benign (Jul 30, 2021)
14-22836941-G-C			Likely benign (May 26, 2023)
14-22836945-C-A			Likely benign (Jul 18, 2022)
14-22837127-TGC-T			Benign (May 24, 2021)
14-22837130-C-T			Benign (May 24, 2021)
14-22837133-C-A			Benign (May 24, 2021)
14-22841276-C-T			Benign (May 14, 2021)
14-22841473-A-G			Likely benign (Nov 14, 2023)
14-22841477-C-T			Likely benign (Feb 06, 2023)
14-22841491-G-C			Likely benign (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MMP14	protein_coding	protein_coding	ENST00000311852	10	12471

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00478	125458	0	290	125748	0.00115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	290	370	0.783	0.0000229	3797
Missense in Polyphen		109	171.81	0.63441		1736
Synonymous	0.244	152	156	0.975	0.0000107	1153
Loss of Function	4.48	3	29.1	0.103	0.00000156	299

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00163	0.00158
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.00535	0.00529
Finnish	0.00147	0.00143
European (Non-Finnish)	0.00102	0.00100
Middle Eastern	0.00535	0.00529
South Asian	0.000262	0.000261
Other	0.00117	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (By similarity). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (PubMed:20837484). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2 (PubMed:12714657). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (PubMed:22330140). {ECO:0000250|UniProtKB:P53690, ECO:0000269|PubMed:12714657, ECO:0000269|PubMed:20837484, ECO:0000269|PubMed:22065321, ECO:0000269|PubMed:22330140}.
• Disease: DISEASE: Winchester syndrome (WNCHRS) [MIM:277950]: A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. {ECO:0000269|PubMed:22922033}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: GnRH signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Matrix Metalloproteinases;Angiogenesis overview;AGE-RAGE pathway;VEGFA-VEGFR2 Signaling Pathway;Senescence and Autophagy in Cancer;inhibition of matrix metalloproteinases;Collagen degradation;Extracellular matrix organization;HIF-2-alpha transcription factor network;Activation of Matrix Metalloproteinases;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.557

Intolerance Scores

• loftool: 0.0497
• rvis_EVS: 0.05
• rvis_percentile_EVS: 57.48

Haploinsufficiency Scores

• pHI: 0.549
• hipred: Y
• hipred_score: 0.785
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.587

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mmp14
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; hearing/vestibular/ear 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); limbs/digits/tail phenotype; digestive/alimentary phenotype; muscle phenotype; reproductive 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); normal phenotype; 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: mmp14b
• Affected structure: auditory capsule
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: skeletal system development;angiogenesis;ovarian follicle development;response to hypoxia;endothelial cell proliferation;endochondral ossification;proteolysis;response to oxidative stress;male gonad development;response to mechanical stimulus;response to hormone;positive regulation of myotube differentiation;positive regulation of protein processing;response to organic cyclic compound;protein processing;extracellular matrix disassembly;extracellular matrix organization;positive regulation of cell growth;lung development;positive regulation of cell migration;collagen catabolic process;zymogen activation;endodermal cell differentiation;chondrocyte proliferation;astrocyte cell migration;response to estrogen;positive regulation of B cell differentiation;negative regulation of Notch signaling pathway;embryonic cranial skeleton morphogenesis;branching morphogenesis of an epithelial tube;tissue remodeling;cell motility;negative regulation of focal adhesion assembly;head development;craniofacial suture morphogenesis;regulation of protein localization to plasma membrane;positive regulation of macrophage migration;response to odorant
• Cellular component: extracellular space;nucleus;cytoplasm;Golgi lumen;cytosol;plasma membrane;integral component of plasma membrane;focal adhesion;extracellular matrix;cytoplasmic vesicle;melanosome;macropinosome;intermediate filament cytoskeleton
• Molecular function: endopeptidase activity;metalloendopeptidase activity;serine-type endopeptidase activity;integrin binding;protein binding;zinc ion binding;metalloaminopeptidase activity