This gene encodes a member of the matrix metalloproteinase family. Proteins in this family are involved in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, and disease processes, such as asthma and tumor metastasis. The encoded protein may play an important role in embryogenesis, p... See more...

Aliases for MMP21 Gene

Aliases for MMP21 Gene

  • Matrix Metallopeptidase 21 2 3 5
  • Matrix Metalloproteinase 21 2 3
  • Matrix Metalloproteinase-21 3 4
  • MMP-21 3 4
  • EC 3.4.24.- 4
  • EC 3.4.24 50
  • MMP21 5
  • HTX7 3

External Ids for MMP21 Gene

Previous GeneCards Identifiers for MMP21 Gene

  • GC10M126430
  • GC10M126658
  • GC10M127496
  • GC10M127029
  • GC10M127445
  • GC10M121144
  • GC10M125766

Summaries for MMP21 Gene

Entrez Gene Summary for MMP21 Gene

  • This gene encodes a member of the matrix metalloproteinase family. Proteins in this family are involved in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, and disease processes, such as asthma and tumor metastasis. The encoded protein may play an important role in embryogenesis, particularly in neuronal cells, as well as in lymphocyte development and survival. [provided by RefSeq, May 2013]

GeneCards Summary for MMP21 Gene

MMP21 (Matrix Metallopeptidase 21) is a Protein Coding gene. Diseases associated with MMP21 include Heterotaxy, Visceral, 7, Autosomal and Visceral Heterotaxy. Among its related pathways are Integrin Pathway and GPCR Pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and metallopeptidase activity. An important paralog of this gene is MMP15.

UniProtKB/Swiss-Prot Summary for MMP21 Gene

  • Plays a specialized role in the generation of left-right asymmetry during embryogenesis. May act as a negative regulator of the NOTCH-signaling pathway (PubMed:26429889, PubMed:26437028). Cleaves alpha-1-antitrypsin (PubMed:12617721).

Tocris Summary for MMP21 Gene

  • Matrix metalloproteases (matrix metalloproteinase, MMPs), also called matrixins, are zinc-dependent endopeptidases and the major proteases in ECM degradation. MMPs are capable of degrading several extracellular molecules and a number of bioactive molecules.

Gene Wiki entry for MMP21 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MMP21 Gene

Genomics for MMP21 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MMP21 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10J125773 Promoter 0.5 Ensembl 250.7 +1.7 1720 0.6 ZBTB33 ZNF48 MMP21 UROS HSALNG0081419 EDRF1
GH10J125775 Promoter 0.3 EPDnew 250.7 +0.0 9 0.1 MMP21 HSALNG0081419 EDRF1
GH10J125816 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 11.4 -41.5 -41479 3 NCOR1 IKZF1 ZNF592 NFIC HES1 MBD2 ARNT NFATC3 NBN TAL1 UROS MMP21 EDRF1 FANK1 MIR4484 lnc-MMP21-2
GH10J125878 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 9.8 -104.4 -104360 3.9 ZNF600 JUND CEBPA ZNF10 CEBPB FOXA1 FEZF1 HOMEZ SIN3A FOXA2 DHX32 UROS MMP21 RF00004-018 ENSG00000277371 RNU2-42P FANK1 BCCIP
GH10J125895 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 4.7 -120.0 -119980 4 LARP7 ZNF600 POLR2A ZIC2 ZBTB10 YY1 MXD4 NONO SMAD5 MBD2 DHX32 FANK1 EDRF1 BCCIP EDRF1-AS1 CTBP2 UROS MMP21 RF00004-018 RNU2-42P
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MMP21 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MMP21

Top Transcription factor binding sites by QIAGEN in the MMP21 gene promoter:
  • GATA-1
  • GATA-2
  • GATA-3
  • HSF2
  • IRF-2
  • Meis-1
  • Meis-1a
  • Meis-1b
  • Oct-B1
  • SEF-1 (1)

Genomic Locations for MMP21 Gene

Latest Assembly
chr10:125,753,580-125,775,821
(GRCh38/hg38)
Size:
22,242 bases
Orientation:
Minus strand

Previous Assembly
chr10:127,455,022-127,464,390
(GRCh37/hg19 by Entrez Gene)
Size:
9,369 bases
Orientation:
Minus strand

chr10:127,455,022-127,464,390
(GRCh37/hg19 by Ensembl)
Size:
9,369 bases
Orientation:
Minus strand

Genomic View for MMP21 Gene

Genes around MMP21 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MMP21 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MMP21 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MMP21 Gene

Proteins for MMP21 Gene

  • Protein details for MMP21 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N119-MMP21_HUMAN
    Recommended name:
    Matrix metalloproteinase-21
    Protein Accession:
    Q8N119
    Secondary Accessions:
    • Q5VZP9
    • Q8NG02

    Protein attributes for MMP21 Gene

    Size:
    569 amino acids
    Molecular mass:
    65043 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Cofactor:
    Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
    Quaternary structure:
    No Data Available

neXtProt entry for MMP21 Gene

Selected DME Specific Peptides for MMP21 Gene

Q8N119:
  • NRTRYGDP
  • PRCGVPD
  • KLGFGRGRHLGC
  • WSEVTPL
  • GISLLKVA

Post-translational modifications for MMP21 Gene

Other Protein References for MMP21 Gene

Antibodies for research

  • Abcam antibodies for MMP21
  • Boster Bio Antibodies for MMP21
  • Santa Cruz Biotechnology (SCBT) Antibodies for MMP21

Domains & Families for MMP21 Gene

Gene Families for MMP21 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for MMP21 Gene

GenScript: Design optimal peptide antigens:
  • Matrix metalloproteinase-21 (MMP21_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N119

UniProtKB/Swiss-Prot:

MMP21_HUMAN :
  • The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
  • Belongs to the peptidase M10A family.
Domain:
  • The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Family:
  • Belongs to the peptidase M10A family.
genes like me logo Genes that share domains with MMP21: view

Function for MMP21 Gene

Molecular function for MMP21 Gene

UniProtKB/Swiss-Prot Function:
Plays a specialized role in the generation of left-right asymmetry during embryogenesis. May act as a negative regulator of the NOTCH-signaling pathway (PubMed:26429889, PubMed:26437028). Cleaves alpha-1-antitrypsin (PubMed:12617721).

Enzyme Numbers (IUBMB) for MMP21 Gene

Phenotypes From GWAS Catalog for MMP21 Gene

Gene Ontology (GO) - Molecular Function for MMP21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004222 metalloendopeptidase activity IBA 21873635
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IEA --
GO:0008270 zinc ion binding IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with MMP21: view
genes like me logo Genes that share phenotypes with MMP21: view

Human Phenotype Ontology for MMP21 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for research

  • Taconic Biosciences Mouse Models for MMP21

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MMP21

No data available for Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for MMP21 Gene

Localization for MMP21 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MMP21 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MMP21 gene
Compartment Confidence
extracellular 4
plasma membrane 2
mitochondrion 2
cytoskeleton 1
nucleus 1
endoplasmic reticulum 1
cytosol 1
golgi apparatus 1
lysosome 0

Gene Ontology (GO) - Cellular Components for MMP21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA 21873635
GO:0031012 extracellular matrix IEA --
genes like me logo Genes that share ontologies with MMP21: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MMP21 Gene

Pathways & Interactions for MMP21 Gene

PathCards logo

SuperPathways for MMP21 Gene

SuperPathway Contained pathways
1 Matrix Metalloproteinases
.69
2 Integrin Pathway
.56
.38
3 GPCR Pathway
.59
genes like me logo Genes that share pathways with MMP21: view

Pathways by source for MMP21 Gene

1 BioSystems pathway for MMP21 Gene
4 Qiagen pathways for MMP21 Gene
  • Inhibition of Matrix Metalloproteinases
  • Pancreatic Adenocarcinoma
  • Transendothelial Migration of Leukocytes
  • UPA-UPAR Pathway

Gene Ontology (GO) - Biological Process for MMP21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002244 hematopoietic progenitor cell differentiation IEA --
GO:0006508 proteolysis IEA --
GO:0007368 determination of left/right symmetry IEA,IMP 26429889
GO:0030198 extracellular matrix organization IBA 21873635
GO:0030574 collagen catabolic process IBA 21873635
genes like me logo Genes that share ontologies with MMP21: view

No data available for SIGNOR curated interactions for MMP21 Gene

Drugs & Compounds for MMP21 Gene

(5) Drugs for MMP21 Gene - From: DrugBank, HMDB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Marimastat Investigational Pharma Target, inhibitor MMPs inhibitor,board spectrum 4
Calcium Nutra 6959
ARP 100 Pharma Selective MMP-2 inhibitor, Selective inhibitor of MMP-2 0
ARP 101 Pharma MMP inhibitor,potent and selective, Inhibitor of MMP-2 0
PD 166793 Pharma MMP inhibitor, Broad spectrum MMP inhibitor 0

(3) Tocris Compounds for MMP21 Gene

Compound Action Cas Number
ARP 100 Selective inhibitor of MMP-2 704888-90-4
ARP 101 Inhibitor of MMP-2 849773-63-3
PD 166793 Broad spectrum MMP inhibitor 199850-67-4
genes like me logo Genes that share compounds with MMP21: view

Transcripts for MMP21 Gene

mRNA/cDNA for MMP21 Gene

1 REFSEQ mRNAs :
2 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MMP21

Alternative Splicing Database (ASD) splice patterns (SP) for MMP21 Gene

No ASD Table

Relevant External Links for MMP21 Gene

GeneLoc Exon Structure for
MMP21

Expression for MMP21 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MMP21 Gene

mRNA differential expression in normal tissues according to GTEx for MMP21 Gene

This gene is overexpressed in Ovary (x4.5).

Protein differential expression in normal tissues from HIPED for MMP21 Gene

This gene is overexpressed in Adipocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MMP21 Gene



Protein tissue co-expression partners for MMP21 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MMP21

SOURCE GeneReport for Unigene cluster for MMP21 Gene:

Hs.314141

mRNA Expression by UniProt/SwissProt for MMP21 Gene:

Q8N119-MMP21_HUMAN
Tissue specificity: Identified in fetal brain, kidney and liver. In adult tissues found primarily in ovary, kidney, liver, lung, placenta, brain and peripheral blood leukocytes. Expressed as well in various cancer cell lines.

Evidence on tissue expression from TISSUES for MMP21 Gene

  • Kidney(4.2)
genes like me logo Genes that share expression patterns with MMP21: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for MMP21 Gene

Orthologs for MMP21 Gene

This gene was present in the common ancestor of animals.

Orthologs for MMP21 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MMP21 29 30
  • 99.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MMP21 29 30
  • 82.69 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Mmp21 29 16 30
  • 78.78 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mmp21 29
  • 77.96 (n)
Oppossum
(Monodelphis domestica)
Mammalia MMP21 30
  • 62 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia MMP21 30
  • 59 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 21 (a)
ManyToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mmp21 29
  • 62.7 (n)
Str.5461 29
African clawed frog
(Xenopus laevis)
Amphibia mmp21-A 29
Zebrafish
(Danio rerio)
Actinopterygii LOC100003089 29
  • 58.79 (n)
MMP21 30
  • 49 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea zmp-1 30
  • 22 (a)
ManyToMany
C31B8.8 30
  • 21 (a)
ManyToMany
H19M22.3 30
  • 20 (a)
ManyToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 39 (a)
OneToOne
Species where no ortholog for MMP21 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for MMP21 Gene

ENSEMBL:
Gene Tree for MMP21 (if available)
TreeFam:
Gene Tree for MMP21 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MMP21: view image
Alliance of Genome Resources:
Additional Orthologs for MMP21

Paralogs for MMP21 Gene

genes like me logo Genes that share paralogs with MMP21: view

Variants for MMP21 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MMP21 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
1027776 Uncertain Significance: Heterotaxy, visceral, 7, autosomal 125,770,448(-) G/A
NM_147191.1(MMP21):c.1123C>T (p.Arg375Cys)
MISSENSE
1027777 Uncertain Significance: Heterotaxy, visceral, 7, autosomal 125,772,307(-) G/A
NM_147191.1(MMP21):c.890C>T (p.Thr297Met)
MISSENSE
976665 Likely Pathogenic: Heterotaxy, visceral, 7, autosomal 125,774,247(-) C/G
NM_147191.1(MMP21):c.281G>C (p.Arg94Pro)
MISSENSE
rs1312300020 Likely Pathogenic: Heterotaxy, visceral, 7, autosomal 125,773,971(-) C/A
NM_147191.1(MMP21):c.557G>T (p.Ser186Ile)
MISSENSE
rs137955225 Pathogenic/Likely Pathogenic: Heterotaxy, visceral, 7, autosomal; Heterotaxia; not provided 125,770,368(-) C/T
NM_147191.1(MMP21):c.1203G>A (p.Trp401Ter)
NONSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MMP21 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for MMP21 Gene

Variant ID Type Subtype PubMed ID
esv2759788 CNV gain 17122850
nsv428241 CNV loss 18775914
nsv832017 CNV loss 17160897

Variation tolerance for MMP21 Gene

Residual Variation Intolerance Score: 53.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.77; 58.04% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MMP21 Gene

Human Gene Mutation Database (HGMD)
MMP21
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MMP21
Leiden Open Variation Database (LOVD)
MMP21

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MMP21 Gene

Disorders for MMP21 Gene

MalaCards: The human disease database

(7) MalaCards diseases for MMP21 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
heterotaxy, visceral, 7, autosomal
  • htx7
visceral heterotaxy
  • heterotaxia
dextrocardia with situs inversus
  • situs inversus totalis
heterotaxy
  • heterotaxia
phonagnosia
- elite association - COSMIC cancer census association via MalaCards
Search MMP21 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MMP21_HUMAN
  • Heterotaxy, visceral, 7, autosomal (HTX7) [MIM:616749]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX7 inheritance is autosomal recessive. {ECO:0000269 PubMed:26429889, ECO:0000269 PubMed:26437028, ECO:0000269 PubMed:26437029}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for MMP21

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MMP21: view

No data available for Genatlas for MMP21 Gene

Publications for MMP21 Gene

  1. A human laterality disorder caused by a homozygous deleterious mutation in MMP21. (PMID: 26429889) Perles Z … Katsanis N (Journal of medical genetics 2015) 3 4 72
  2. MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates. (PMID: 26437028) Guimier A … Gordon CT (Nature genetics 2015) 3 4 72
  3. The matrix metalloproteinase-21 gene 572C/T polymorphism and the risk of breast cancer. (PMID: 15015597) Shagisultanova EI … Malkhosyan SR (Anticancer research 2004) 3 22 40
  4. Matrix metalloproteinase-21, the human orthologue for XMMP, is expressed during fetal development and in cancer. (PMID: 12490321) Ahokas K … Saarialho-Kere U (Gene 2002) 3 4 22
  5. Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families. (PMID: 26437029) Akawi N … DDD study (Nature genetics 2015) 4 72

Products for MMP21 Gene

Sources for MMP21 Gene