MMP13

matrix metallopeptidase 13, the group of M10 matrix metallopeptidases|Receptor ligands

Basic information

Region (hg38): 11:102942994-102955732

Links

ENSG00000137745 ∙ NCBI:4322 ∙ OMIM:600108 ∙ HGNC:7159 ∙ Uniprot:P45452 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia, Missouri type (Definitive), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia, Missouri type (Definitive), mode of inheritance: AR
• metaphyseal anadysplasia (Supportive), mode of inheritance: AD
• metaphyseal chondrodysplasia, Spahr type (Supportive), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, Missouri type (Supportive), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia, Missouri type (Strong), mode of inheritance: AD
• metaphyseal chondrodysplasia, Spahr type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasia, Missouri type (Metaphyseal anadysplasia 1); Metaphyseal dysplasia, Spahr type	AD/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	13915518; 16167086; 19615667; 24648384; 24781753

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MMP13 gene.

• not provided (200 variants)
• Spondyloepimetaphyseal dysplasia, Missouri type (57 variants)
• Metaphyseal anadysplasia (53 variants)
• Inborn genetic diseases (14 variants)
• Metaphyseal chondrodysplasia, Spahr type (6 variants)
• not specified (3 variants)
• Spondyloepimetaphyseal dysplasia (3 variants)
• Metaphyseal anadysplasia 1, autosomal dominant (2 variants)
• MMP13-Related Disorders (2 variants)
• MMP13-related condition (1 variants)
• Spondyloepimetaphyseal dysplasia, Missouri type;Metaphyseal chondrodysplasia, Spahr type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMP13 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			1	28	1	30
missense	3	3	92	5		103
nonsense	3	1	1			5
start loss						0
frameshift	2	2	1			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)		7				7
splice region			1	5	2	8
non coding			16	24	25	65
Total	8	13	113	57	26

Highest pathogenic variant AF is 0.0000328

Variants in MMP13

This is a list of pathogenic ClinVar variants found in the MMP13 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-102943047-T-G		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-102943095-G-T		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Uncertain significance (Jan 13, 2018)
11-102943164-A-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 13, 2018)
11-102943214-A-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 13, 2018)
11-102943259-A-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 12, 2018)
11-102943268-T-TA		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia	Benign (May 19, 2021)
11-102943312-C-G		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Uncertain significance (Jan 13, 2018)
11-102943381-T-C		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Benign (Jan 12, 2018)
11-102943414-G-A		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 12, 2018)
11-102943416-T-TA		Spondyloepimetaphyseal dysplasia • Metaphyseal anadysplasia	Uncertain significance (Jun 14, 2016)
11-102943495-A-C		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Uncertain significance (Jan 13, 2018)
11-102943510-T-C		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 13, 2018)
11-102943543-T-A		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 13, 2018)
11-102943638-T-C		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Benign/Likely benign (Jan 13, 2018)
11-102943830-C-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 12, 2018)
11-102943840-T-C		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Benign/Likely benign (Jan 13, 2018)
11-102943889-A-AATG		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia	Uncertain significance (Jun 14, 2016)
11-102943952-A-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Benign/Likely benign (Apr 12, 2019)
11-102943991-A-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 13, 2018)
11-102944002-G-A		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Uncertain significance (Jan 12, 2018)
11-102944106-C-T		Metaphyseal anadysplasia • Spondyloepimetaphyseal dysplasia, Missouri type	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-102944110-T-C		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-102944212-A-G		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Uncertain significance (Jan 13, 2018)
11-102944253-T-A		Spondyloepimetaphyseal dysplasia, Missouri type • Metaphyseal anadysplasia	Conflicting classifications of pathogenicity (Jan 12, 2018)
11-102944265-CTT-C		Metaphyseal chondrodysplasia, Spahr type	Uncertain significance (Mar 05, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MMP13	protein_coding	protein_coding	ENST00000260302	10	12740

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.88e-18	0.00216	125675	0	71	125746	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.210	268	259	1.04	0.0000141	3141
Missense in Polyphen		97	109.04	0.88957		1284
Synonymous	-0.108	97	95.7	1.01	0.00000587	870
Loss of Function	-0.408	25	22.9	1.09	0.00000123	274

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000746	0.000746
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000363	0.000360
Middle Eastern	0.000218	0.000217
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion. {ECO:0000269|PubMed:16167086, ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229, ECO:0000269|PubMed:19615667, ECO:0000269|PubMed:20726512, ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497, ECO:0000269|PubMed:8207000, ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:8603731, ECO:0000269|PubMed:8663255, ECO:0000269|PubMed:9065415}.
• Disease: DISEASE: Spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:602111]: A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age. {ECO:0000269|PubMed:16167086}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111]: 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.; DISEASE: Metaphyseal dysplasia, Spahr type (MDST) [MIM:250400]: An autosomal recessive, rare disease characterized by moderate short stature, mild genua vara, and radiographic signs of metaphyseal dysplasia, but no biochemical signs of rickets. {ECO:0000269|PubMed:24648384, ECO:0000269|PubMed:24781753}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Matrix Metalloproteinases;AGE-RAGE pathway;Oncostatin M Signaling Pathway;Endochondral Ossification;RUNX2 regulates genes involved in cell migration;Transcriptional regulation by RUNX2;Assembly of collagen fibrils and other multimeric structures;Gene expression (Transcription);Generic Transcription Pathway;Collagen degradation;RNA Polymerase II Transcription;Collagen formation;Extracellular matrix organization;Activation of Matrix Metalloproteinases;Degradation of the extracellular matrix;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.637

Intolerance Scores

• loftool: 0.858
• rvis_EVS: -0.96
• rvis_percentile_EVS: 9.17

Haploinsufficiency Scores

• pHI: 0.373
• hipred: N
• hipred_score: 0.451
• ghis: 0.398

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.659

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mmp13
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; skeleton phenotype; limbs/digits/tail 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)

Zebrafish Information Network

• Gene name: mmp13a
• Affected structure: caudal fin actinotrichium
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: endochondral ossification;growth plate cartilage development;proteolysis;extracellular matrix disassembly;extracellular matrix organization;bone mineralization;collagen catabolic process;cellular protein metabolic process;bone morphogenesis
• Cellular component: extracellular region;extracellular space;extracellular matrix
• Molecular function: metalloendopeptidase activity;serine-type endopeptidase activity;calcium ion binding;collagen binding;zinc ion binding