GeneBe

MMP13

protein-coding

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

Gene summary

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

MANE transcript

NM_002427.4

Inheritance

AR, AD

ClinVar variants

P:34U:189B:68

Top phenotype

Spondyloepimetaphyseal dysplasia, Missouri type (Metaphyseal anadysplasia 1); Metaphyseal dysplasia, Spahr type

gnomAD constraint

pLI —, LoF o/e 1.09

Max pathogenic AF

—

Genomic locus

chr11:102,942,995-102,955,732

External References & Databases

Ensembl (ENSG00000137745)NCBI Gene (4322)OMIM (600108)HGNC:7159GenCCUniProt (P45452)AlphaFoldClinVar (MMP13)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~12.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

metaphyseal chondrodysplasia, Spahr typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009597

Submitter: Ambry Genetics

spondyloepimetaphyseal dysplasia, Missouri typeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011198

Submitter: G2P

spondyloepimetaphyseal dysplasia, Missouri typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011198

Submitter: PanelApp Australia

spondyloepimetaphyseal dysplasia, Missouri typeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0011198

Submitter: Ambry Genetics

spondyloepimetaphyseal dysplasia, Missouri typeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011198

Submitter: Orphanet

metaphyseal chondrodysplasia, Spahr typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009597

Submitter: Labcorp Genetics (formerly Invitae)

spondyloepimetaphyseal dysplasia, Missouri typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011198

Submitter: Labcorp Genetics (formerly Invitae)

metaphyseal chondrodysplasia, Spahr typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009597

Submitter: G2P

metaphyseal anadysplasiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015177

Submitter: Orphanet

metaphyseal chondrodysplasia, Spahr typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009597

Submitter: Orphanet

metaphyseal chondrodysplasia, Spahr typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009597

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spondyloepimetaphyseal dysplasia, Missouri type (Metaphyseal anadysplasia 1); Metaphyseal dysplasia, Spahr typeAD/AR

Manifestation: Musculoskeletal

Intervention: General

Rationale: 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

Refs: 13915518; 16167086; 19615667; 24648384; 24781753Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MMP13 variants in ClinVar

8 Conditions Cataloged
not providedTotal: 291
not specifiedTotal: 83
Spondyloepimetaphyseal dysplasia, Missouri typeTotal: 42
Metaphyseal anadysplasiaTotal: 27
Metaphyseal chondrodysplasia, Spahr typeTotal: 14
MMP13-related disorderTotal: 6
Metaphyseal anadysplasia 1, autosomal dominantTotal: 4
Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002427.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
56
clinvar
 59
missense
4
clinvar
7
clinvar
181
clinvar
12
clinvar
 204
nonsense
3
clinvar
2
clinvar
 5
start loss
1
clinvar
 1
frameshift
5
clinvar
3
clinvar
2
clinvar
 10
splice donor/acceptor (+/-2bp)
10
clinvar
2
clinvar
 12
Total1222189680291

Highest pathogenic variant AF is 0.00006197553

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002427.4RefSeqNP_002418.110MANE Select
ENST00000260302.8EnsemblENSP00000260302.310MANE Select
ENST00000340273.4EnsemblENSP00000339672.411Standard
ENST00000857540.1EnsemblENSP00000527599.110Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
mmp13aDanio rerio

Structure: caudal fin actinotrichium

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Relaxin signaling pathway - Homo sapiens (human)
  • IL-17 signaling pathway - Homo sapiens (human)
  • Matrix Metalloproteinases
  • AGE-RAGE pathway
  • Oncostatin M Signaling Pathway

Biological Process

  • endochondral ossification
  • growth plate cartilage development
  • proteolysis
  • extracellular matrix disassembly
  • extracellular matrix organization

Molecular Function

  • metalloendopeptidase activity
  • serine-type endopeptidase activity
  • calcium ion binding
  • collagen binding
  • zinc ion binding

Cellular Component

  • extracellular region
  • extracellular space
  • extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000260302
Coding exons
10
Length
12740
Individuals with no LoFs
125675
Homozygous LoFs
0
Heterozygous LoFs
71
Defined
125746
p
0.000282
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.2102682591.040.00001413141
Missense (PolyPhen)97109.040.889571284
Synonymous-0.1089795.71.010.00000587870
Loss of Function-0.4082522.91.090.00000123274

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000370.00037rare
Latino/Admixed American0.000380.00038rare
Ashkenazi Jewish00.0absent
East Asian0.000220.00022rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000360.00036rare
South Asian0.000160.00016rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.637

Intolerance Scores

LoFtool
0.858
RVIS EVS
-0.96
RVIS percentile EVS
9.17

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.659

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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