MMP21 (matrix metallopeptidase 21)

Gene

• Entrez ID: 118856
• Gene name: Matrix metallopeptidase 21
• Gene symbol: MMP21
• Synonyms (NCBI Gene): HTX7, MMP-21
• Chromosome: 10
• Chromosome location: 10q26.2
• Summary: 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, a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137955225	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs145119918	G>A,C	Pathogenic, likely-pathogenic	Stop gained, missense variant, coding sequence variant
rs145789868	C>T	Pathogenic	Coding sequence variant, missense variant
rs886041273	->G	Pathogenic	Coding sequence variant, frameshift variant
rs948481222	A>C	Likely-pathogenic	Coding sequence variant, stop gained
rs1312300020	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT733695	hsa-miR-4484	qRT-PCR	31582779
MIRT733695	hsa-miR-4484	qRT-PCR	31582779
MIRT733695	hsa-miR-4484	Microarray, qRT-PCR	31582779

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002244	Process	Hematopoietic progenitor cell differentiation	IEA
GO:0004222	Function	Metalloendopeptidase activity	IBA
GO:0004222	Function	Metalloendopeptidase activity	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0006508	Process	Proteolysis	IEA
GO:0007368	Process	Determination of left/right symmetry	IEA
GO:0007368	Process	Determination of left/right symmetry	IEA
GO:0007368	Process	Determination of left/right symmetry	IMP	26429889, 26437028
GO:0008233	Function	Peptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030198	Process	Extracellular matrix organization	IBA
GO:0030574	Process	Collagen catabolic process	IBA
GO:0031012	Component	Extracellular matrix	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060976	Process	Coronary vasculature development	IEA
GO:0061371	Process	Determination of heart left/right asymmetry	IEA
GO:0061371	Process	Determination of heart left/right asymmetry	ISS

Other IDs

• MIM: 608416
• HGNC: 14357
• e!Ensembl: ENSG00000154485

Protein

• UniProt ID: Q8N119
• Protein name: Matrix metalloproteinase-21 (MMP-21) (EC 3.4.24.-)
• Protein 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). {ECO:00002
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01471	PG_binding_1	46 → 112	Putative peptidoglycan binding domain	Domain
  PF00413	Peptidase_M10	170 → 327	Matrixin	Domain
  PF00045	Hemopexin	353 → 391	Hemopexin	Repeat
  PF00045	Hemopexin	400 → 449	Hemopexin	Repeat
  PF00045	Hemopexin	451 → 496	Hemopexin	Repeat

• Tissue specificity: 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. {ECO:0000269|PubMed:12490321,
• Sequence:

  MLAASIFRPTLLLCWLAAPWPTQPESLFHSRDRSDLEPSPLRQAKPIADLHAAQRFLSRY
  GWSGVWAAWGPSPEGPPETPKGAALAEAVRRFQRANALPASGELDAATLAAMNRPRCGVP
  DMRPPPPSAPPSPPGPPPRARSRRSPRAPLSLSRRGWQPRGYPDGGAAQAFSKRTLSWRL
  LGEALSSQLSVADQRRIVALAFRMWSEVTPLDFREDLAAPGAAVDIKLGFGRGRHLGCPR
  AFDGSGQEFAHAWRLGDIHFDDDEHFTPPTSDTGISLLKVAVHEIGHVLGLPHTYRTGSI
  MQPNYIPQEPAFELDWSDRKAIQKLYGSCEGSFDTAFDWIRKERNQYGEVMVRFSTYFFR
  NSWYWLYENRNNRTRYGDPIQILTGWPGIPTHNIDAFVHIWTWKRDERYFFQGNQYWRYD
  SDKDQALTEDEQGKSYPKLISEGFPGIPSPLDTAFYDRRQKLIYFFKESLVFAFDVNRNR
  VLNSYPKRITEVFPAVIPQNHPFRNIDSAYYSYAYNSIFFFKGNAYWKVVNDKDKQQNSW
  LPANGLFPKKFISEKWFDVCDVHISTLNM

• Sequence length: 569

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Heterotaxy, visceral, 7, autosomal	Likely pathogenic; Pathogenic	rs145119918, rs886041273, rs1795441247, rs137955225, rs2493742377, rs1487834487, rs781127723, rs1850488424, rs773125891, rs1434829861, rs1432707846, rs747668147, rs777088158, rs145789868, rs1312300020	RCV001254033 RCV001782764 RCV003239332 RCV004543121 RCV003985984 RCV004544237 RCV004544238 RCV004544239 RCV004544241 RCV004544242 RCV004544243 RCV004544244 RCV004544245 RCV000754882 RCV000754883	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MMP21-related disorder	Likely pathogenic; Pathogenic	rs886041273, rs2493740568, rs2493743195	RCV003409394 RCV003406106 RCV003969485	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Visceral heterotaxy	Likely pathogenic; Pathogenic	rs145119918, rs137955225	RCV000826118 RCV000600696	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
DERMATOLOGIC DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HETEROTAXY SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SITUS AMBIGUUS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SITUS INVERSUS	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SITUS INVERSUS TOTALIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES, GENETIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TETRALOGY OF FALLOT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Asplenia Syndrome	Asplenia	CTD_human_DG	26437028		★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	15015597		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	15015597	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	16641547	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	12490321		★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	Pubtator	16641547	Associate	★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	39976347	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	21656525		★☆☆☆☆ Found in Text Mining only
Congenital atresia of pulmonary artery	Congenital Atresia Of Pulmonary Artery	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital malrotation of intestine	Congenital malrotation of intestine	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cutaneous Fibrous Histiocytoma	Fibrous Histiocytoma	BEFREE	16984259		★☆☆☆☆ Found in Text Mining only
Cutaneous Fibrous Histiocytoma	Fibrous Histiocytoma	CTD_human_DG	16984259		★☆☆☆☆ Found in Text Mining only
Delirium, Dementia, Amnestic, Cognitive Disorders	Delirium, Dementia, Amnestic, Cognitive Disorders	BEFREE	29575199		★☆☆☆☆ Found in Text Mining only
Dermatologic disorders	Dermatologic Disorders	CTD_human_DG	16984259		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	16641547, 36437782	Associate	★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	39976347	Associate	★☆☆☆☆ Found in Text Mining only
Heart Septal Defects Ventricular	Congenital heart septal defect	Pubtator	39976347	Associate	★☆☆☆☆ Found in Text Mining only
Heterotaxy Syndrome	Heterotaxia	CLINVAR_DG	26437028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heterotaxy Syndrome	Heterotaxia	CTD_human_DG	26437028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HETEROTAXY, VISCERAL, 7, AUTOSOMAL	Heterotaxy, Visceral	GENOMICS_ENGLAND_DG	26429889, 26437028		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
HETEROTAXY, VISCERAL, 7, AUTOSOMAL	Heterotaxy, Visceral	UNIPROT_DG	26429889, 26437028, 26437029		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
HETEROTAXY, VISCERAL, 7, AUTOSOMAL	Heterotaxy, Visceral	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
HETEROTAXY, VISCERAL, 7, AUTOSOMAL	Heterotaxy, Visceral	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Histiocytoma, Benign Fibrous	Benign fibrous histiocytoma	CTD_human_DG	16984259		★☆☆☆☆ Found in Text Mining only
Interrupted aortic arch	Interrupted aortic arch	HPO_DG			★☆☆☆☆ Found in Text Mining only
Interrupted inferior vena cava with azygous continuation	Interrupted inferior vena cava with azygous continuation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Left Atrial Isomerism	Left atrial isomerism	CTD_human_DG	26437028		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	18768525		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	LHGDN	18768525		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic Metastasis	BEFREE	24700287		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	15015597		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	29731903		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	12490321, 14691307		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	14691307		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	39976347	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16641547, 19921252		★☆☆☆☆ Found in Text Mining only
Neurocognitive Disorders	Neurocognitive Disorders	BEFREE	29575199		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	17873896	Associate	★☆☆☆☆ Found in Text Mining only
Polysplenia	Polysplenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polysplenia Syndrome	Polysplenia	CTD_human_DG	26437028		★☆☆☆☆ Found in Text Mining only
Right Atrial Isomerism	Atrial Isomerism	CTD_human_DG	26437028		★☆☆☆☆ Found in Text Mining only
Situs ambiguous	Situs ambiguus	ORPHANET_DG	26437029		★☆☆☆☆ Found in Text Mining only
Situs ambiguus	Situs ambiguus	BEFREE	26429889, 26437028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs ambiguus	Situs ambiguus	CTD_human_DG	26437028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs ambiguus	Situs ambiguus	ORPHANET_DG	26437029		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs ambiguus	Situs ambiguus	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs Inversus	Situs Inversus	ORPHANET_DG	26429889, 26437028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs inversus totalis	Situs Inversus	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Skin lesion	Skin Lesion	BEFREE	16984259		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	24700287		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	16641547, 31016793		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	29731903		★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	31582779		★☆☆☆☆ Found in Text Mining only
Total anomalous pulmonary venous return	Pulmonary Venous Return Anomaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uhl anomaly	Uhl anomaly	HPO_DG			★☆☆☆☆ Found in Text Mining only