GeneBe

MMP20

protein-coding

matrix metallopeptidase 20, the group of M10 matrix metallopeptidases

Gene summary

Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3. [provided by RefSeq, Aug 2011]

MANE transcript

NM_004771.4

Inheritance

AR

ClinVar variants

P:14U:119B:16

Top phenotype

Amelogenesis imperfecta, hypomaturation type, IIA2

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr11:102,576,832-102,625,332

External References & Databases

Ensembl (ENSG00000137674)NCBI Gene (9313)OMIM (604629)HGNC:7167GenCCUniProt (O60882)AlphaFoldClinVar (MMP20)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~48.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta hypomaturation type 2A2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012926

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015048

Submitter: Orphanet

amelogenesis imperfecta hypomaturation type 2A2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012926

Submitter: PanelApp Australia

amelogenesis imperfecta hypomaturation type 2A2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012926

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, hypomaturation type, IIA2AR

Manifestation: Dental

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: 3150442; 15744043; 21597265; 23355523Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MMP20 variants in ClinVar

7 Conditions Cataloged
Inborn genetic diseasesTotal: 88
Amelogenesis imperfecta hypomaturation type 2A2Total: 60
not providedTotal: 24
MMP20-related disorderTotal: 13
not specifiedTotal: 1
SchizophreniaTotal: 1
Intellectual disability, autosomal dominant 56Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004771.4. 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
14
clinvar
5
clinvar
1
clinvar
 20
missense
4
clinvar
3
clinvar
104
clinvar
9
clinvar
1
clinvar
 121
nonsense
1
clinvar
3
clinvar
 4
start loss
0
frameshift
1
clinvar
1
clinvar
 2
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total77119142149

Highest pathogenic variant AF is 0.0023370972

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004771.4RefSeqNP_004762.210MANE Select
ENST00000260228.3EnsemblENSP00000260228.210MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Matrix Metalloproteinases
  • Assembly of collagen fibrils and other multimeric structures
  • Collagen degradation
  • Collagen formation
  • Extracellular matrix organization

Biological Process

  • proteolysis
  • extracellular matrix disassembly
  • protein catabolic process
  • extracellular matrix organization
  • collagen catabolic process

Molecular Function

  • metalloendopeptidase activity
  • serine-type endopeptidase activity
  • protein 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
ENST00000260228
Coding exons
10
Length
48498
Individuals with no LoFs
125422
Homozygous LoFs
0
Heterozygous LoFs
326
Defined
125748
p
0.00130
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.5673012751.100.00001523172
Missense (PolyPhen)9694.9361.01121064
Synonymous-1.751261031.220.00000619930
Loss of Function0.2222122.10.9499.41e-7285

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000450.00043rare
Latino/Admixed American0.00140.0013notable
Ashkenazi Jewish00.0absent
East Asian0.000760.00076rare
Finnish0.000230.00023rare
European (Non-Finnish)0.00210.0020notable
South Asian0.000420.00042rare
Other0.00210.0020notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP). May play a central role in tooth enamel formation. Cleaves aggrecan at the '360-Asn-|-Phe-361' site. {ECO:0000269|PubMed:10922468, ECO:0000269|PubMed:9398237}.;
Disease
DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A2 (AI2A2) [MIM:612529]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. {ECO:0000269|PubMed:15744043}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.141

Intolerance Scores

LoFtool
0.714
RVIS EVS
1.42
RVIS percentile EVS
94.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0774

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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