MMP21

Summary

MMP21 (matrix metallopeptidase 21, HGNC:14357) is a protein-coding gene on chromosome 10q26.2, encoding Matrix metalloproteinase-21 (Q8N119). Plays a specialized role in the generation of left-right asymmetry during embryogenesis.

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.

Source: NCBI Gene 118856 — RefSeq curated summary.

At a glance

• Gene–disease (curated): heterotaxy, visceral, 7, autosomal (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 176 total — 11 pathogenic, 9 likely-pathogenic
• MANE Select transcript: NM_147191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14357
Approved symbol	MMP21
Name	matrix metallopeptidase 21
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000154485
Ensembl biotype	protein_coding
OMIM	608416
Entrez	118856

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000368808, ENST00000651834, ENST00000651977, ENST00000652044

RefSeq mRNA: 1 — MANE Select: NM_147191 NM_147191

CCDS: CCDS7647

Canonical transcript exons

ENST00000368808 — 7 exons

Exon	Start	End
ENSE00001016161	125772611	125772750
ENSE00001016164	125772218	125772359
ENSE00001016165	125770334	125770591
ENSE00001016168	125767532	125767704
ENSE00001448003	125766453	125766961
ENSE00001448004	125775660	125775821
ENSE00003843060	125773831	125774365

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 88.02.

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.02	gold quality
corpus epididymis	UBERON:0004359	81.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.21	gold quality
left ovary	UBERON:0002119	73.25	gold quality
right ovary	UBERON:0002118	71.65	gold quality
body of pancreas	UBERON:0001150	68.81	gold quality
ovary	UBERON:0000992	68.02	gold quality
minor salivary gland	UBERON:0001830	66.90	gold quality
ectocervix	UBERON:0012249	65.71	gold quality
right atrium auricular region	UBERON:0006631	65.53	gold quality
right uterine tube	UBERON:0001302	65.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.39	gold quality
body of uterus	UBERON:0009853	65.27	gold quality
cardiac atrium	UBERON:0002081	64.89	gold quality
endocervix	UBERON:0000458	64.83	gold quality
cerebellar hemisphere	UBERON:0002245	64.76	gold quality
cerebellar cortex	UBERON:0002129	64.72	gold quality
metanephros cortex	UBERON:0010533	64.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.73	gold quality
lower esophagus	UBERON:0013473	63.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	63.64	gold quality
ventricular zone	UBERON:0003053	63.57	gold quality
mouth mucosa	UBERON:0003729	63.47	gold quality
right lobe of thyroid gland	UBERON:0001119	63.36	gold quality
saliva-secreting gland	UBERON:0001044	63.29	gold quality
tibial nerve	UBERON:0001323	63.26	gold quality
body of stomach	UBERON:0001161	63.18	gold quality
left lobe of thyroid gland	UBERON:0001120	63.05	gold quality
pancreas	UBERON:0001264	62.85	gold quality
cerebellum	UBERON:0002037	62.82	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting MMP21, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-361-5P	98.95	70.16	1340

Literature-anchored findings (GeneRIF, showing 18)

• The MMP-21 gene 572C/T polymorphism has no significant effect on the development and progression of breast cancer. (PMID:15015597)
• During esophageal tumorigenesis, MMP-21 and MMP-26 have different, unique expression patterns. (PMID:16641547)
• results suggest that MMP-21 and MMP-26 are not only associated with cancer but may be important in connective tissue remodelling and pathobiology of various benign skin disorde (PMID:16984259)
• MMP-21 is not a marker of invasiveness, but rather of differentiation, in pancreatic cancer (PMID:17873896)
• MMP-21 may be an important protease in the terminal differentiation of keratinocytes (PMID:18633436)
• A nonsynchronous polymorphism in the MMP-21 promoter does not significantly confer susceptibility to hepatocellular carcinoma in a southern Chinese population. (PMID:18768525)
• MMP-21 does not associate with invasion of squamous cell cancer but may be involved in keratinocyte differentiation. (PMID:19601983)
• MMP-21 was expressed by Merkel cell carcinoma cells in 13/43 cases and in eight samples by stromal neutrophils. None of the samples with MMP-21-expressing neutrophils had metastasized to the lymph nodes (PMID:19921252)
• MMP-21 expression is elevated in primary CRC and related to tumor invasion and metastasis. MMP-21 was also proved to be an independent prognostic factor for patients with stage II and stage III colorectal cancer. (PMID:21656525)
• analysis proved MMP-21 to be an independent prognostic factor for overall survival of gastric cancer patients (PMID:23275114)
• These results suggest that high MMP-21 expression in lymph node metastatic foci can be used to predict survival in OSCC patients with LNM (PMID:24700287)
• Increased MMP-21 expression in esophageal squamous cell carcinoma is associated with progression and lymph node metastasis. (PMID:25015395)
• loss of MMP21 as a cause of heterotaxy in humans with concomitant defects in Notch signaling. (PMID:26429889)
• Data show that MMP21 (encoding matrix metallopeptidase 21) point mutations were verified by Sanger sequencing, and segregation analysis indicated recessive inheritance. (PMID:26437028)
• MMP-21 572TT genotype increased the risk for the HIV-associated neurocognitive disorder. (PMID:29575199)
• TWIST1, MMP-21, and HLAG-1 co-overexpression is associated with ESCC aggressiveness. (PMID:31016793)
• A novel miRNA-4484 is up-regulated on microarray and associated with increased MMP-21 expression in serum of systemic sclerosis patients. (PMID:31582779)
• De novo disruptive heterozygous MMP21 variants are potential predisposing genetic risk factors in Chinese Han heterotaxy children. (PMID:36123719)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp21	ENSDARG00000112495
mus_musculus	Mmp21	ENSMUSG00000030981
rattus_norvegicus	Mmp21	ENSRNOG00000017756
caenorhabditis_elegans		WBGENE00010423

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-21 — Q8N119 (reviewed: Q8N119)

All UniProt accessions (4): Q8N119, A0A494C0E5, A0A494C1E5, A0A494C1J6

UniProt curated annotations — full annotation on UniProt →

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. Cleaves alpha-1-antitrypsin.

Subcellular location. Secreted.

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.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. 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.

Similarity. Belongs to the peptidase M10A family.

RefSeq proteins (1): NP_671724* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR002477	Peptidoglycan-bd-like	Domain
IPR006026	Peptidase_Metallo	Domain
IPR018487	Hemopexin-like_repeat	Repeat
IPR021190	Pept_M10A	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471

UniProt features (35 total): sequence variant 17, binding site 4, repeat 4, compositionally biased region 2, signal peptide 1, propeptide 1, active site 1, glycosylation site 1, disulfide bond 1, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N119-F1	84.44	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 284

Ligand- & substrate-binding residues (4): 117 (in inhibited form); 283; 287; 293

Disulfide bonds (1): 329–560

Glycosylation sites (1): 372

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_SPECIFICATION_OF_SYMMETRY, TCF4_Q5, LEF1_Q6, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, ROVERSI_GLIOMA_COPY_NUMBER_DN, GOBP_COLLAGEN_CATABOLIC_PROCESS, GOBP_COLLAGEN_METABOLIC_PROCESS, GOCC_EXTERNAL_ENCAPSULATING_STRUCTURE, MIR551B_5P, MIR6844

GO Biological Process (7): hematopoietic progenitor cell differentiation (GO:0002244), proteolysis (GO:0006508), determination of left/right symmetry (GO:0007368), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), coronary vasculature development (GO:0060976), determination of heart left/right asymmetry (GO:0061371)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
heart development	2
hemopoiesis	1
cell differentiation	1
protein metabolic process	1
determination of bilateral symmetry	1
left/right pattern formation	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
blood vessel development	1
determination of left/right symmetry	1
endopeptidase activity	1
metallopeptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP21	CDK13	Q14004	848
MMP21	CDK11A	Q9UQ88	767
MMP21	CDK11B	P21127	763
MMP21	HPX	P02790	720
MMP21	FURIN	P09958	610
MMP21	CFAP52	Q8N1V2	529
MMP21	CFAP53	Q96M91	501
MMP21	PKD1L1	Q8TDX9	493
MMP21	LLGL2	Q6P1M3	410
MMP21	ZIC3	O60481	400
MMP21	CFC1	P0CG37	394
MMP21	GAPDHS	O14556	360
MMP21	ACVR2B	Q13705	348
MMP21	TIMP3	P35625	345
MMP21	TIMP2	P16035	340

IntAct

0 interactions, top by confidence:

BioGRID (2): MMP21 (Affinity Capture-MS), MMP21 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0N9E2K8, A0A1D5NSK0, A0A8M9PFP2, G5ECS8, G5EFD9, O15072, O18767, O43909, O60882, O62806, O77656, O93470, P07152, P22003, P23097, P28825, P29788, P33435, P49003, P57748, P79287, Q10835, Q11005, Q14703, Q16819, Q16820, Q19791, Q24025, Q3U435, Q568B8, Q61847, Q64230, Q6GQB9, Q6NP60, Q8CGD2, Q8K3F2, Q8N119, Q8R4K8, Q8VDA1, Q90YC2

Diamond homologs: A0A0N9E2K8, D0EM77, G5EBU3, O04529, O54732, O55761, O75900, O88272, O88676, O93470, P04004, P22458, P22757, P41245, P48819, P50280, P51511, P53690, P55032, Q02853, Q10739, Q196W5, Q2TBM7, Q499S5, Q5XF51, Q8K3F2, Q8N119, Q90YC2, Q99542, Q9NRE1, A4KX75, O18733, O18767, O18927, O23507, O55123, O60882, O62806, O77656, P03956

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MMP21	up-regulates	ECM_disassembly
MMP21	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

176 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	9
Uncertain significance	116
Likely benign	22
Benign	7

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1275820	NM_147191.1(MMP21):c.937G>T (p.Glu313Ter)	Pathogenic
3235109	NM_147191.1(MMP21):c.1025_1026del (p.Lys342fs)	Pathogenic
3235111	NM_147191.1(MMP21):c.677T>C (p.Ile226Thr)	Pathogenic
3235112	NM_147191.1(MMP21):c.365del (p.Met122fs)	Pathogenic
3235113	NC_000010.11:g.125772345_125778250del	Pathogenic
3235115	NM_147191.1(MMP21):c.961G>C (p.Ala321Pro)	Pathogenic
3235117	NM_147191.1(MMP21):c.847C>T (p.His283Tyr)	Pathogenic
3235118	NM_147191.1(MMP21):c.947G>A (p.Trp316Ter)	Pathogenic
3235119	NM_147191.1(MMP21):c.854T>C (p.Ile285Thr)	Pathogenic
3235120	NM_147191.1(MMP21):c.1380_1381del (p.Lys461fs)	Pathogenic
4075076	NM_147191.1(MMP21):c.1260C>G (p.Asp420Glu)	Pathogenic
1197221	NM_147191.1(MMP21):c.356T>G (p.Val119Gly)	Likely pathogenic
2507421	NM_147191.1(MMP21):c.1303del (p.Ser435fs)	Likely pathogenic
2632338	NM_147191.1(MMP21):c.738del (p.Gln247fs)	Likely pathogenic
3054546	NM_147191.1(MMP21):c.401del (p.Pro134fs)	Likely pathogenic
3062262	NM_147191.1(MMP21):c.614G>A (p.Trp205Ter)	Likely pathogenic
3779882	NM_147191.1(MMP21):c.765dup (p.Gly256fs)	Likely pathogenic
504278	NM_147191.1(MMP21):c.1539T>G (p.Tyr513Ter)	Likely pathogenic
545547	NM_147191.1(MMP21):c.643G>A (p.Glu215Lys)	Likely pathogenic
545548	NM_147191.1(MMP21):c.557G>T (p.Ser186Ile)	Likely pathogenic

SpliceAI

1276 predictions. Top by Δscore:

Variant	Effect	Δscore
10:125753689:TTTA:T	acceptor_loss	1.0000
10:125753690:TTA:T	acceptor_loss	1.0000
10:125753691:TAGCC:T	acceptor_loss	1.0000
10:125753692:A:AG	acceptor_gain	1.0000
10:125753692:AGCCT:A	acceptor_loss	1.0000
10:125753693:G:GA	acceptor_gain	1.0000
10:125753693:GC:G	acceptor_gain	1.0000
10:125753693:GCCTA:G	acceptor_gain	1.0000
10:125753843:AAGG:A	donor_loss	1.0000
10:125753845:GGTAA:G	donor_loss	1.0000
10:125753846:GTAA:G	donor_loss	1.0000
10:125753847:T:A	donor_loss	1.0000
10:125763293:A:AG	acceptor_gain	1.0000
10:125763294:A:G	acceptor_gain	1.0000
10:125763298:TAGC:T	acceptor_loss	1.0000
10:125763299:A:AG	acceptor_gain	1.0000
10:125763299:A:G	acceptor_loss	1.0000
10:125763300:G:GG	acceptor_gain	1.0000
10:125763300:GC:G	acceptor_gain	1.0000
10:125763300:GCA:G	acceptor_gain	1.0000
10:125763300:GCAAT:G	acceptor_gain	1.0000
10:125767701:TTTC:T	acceptor_gain	1.0000
10:125767705:C:CA	acceptor_loss	1.0000
10:125767706:T:G	acceptor_loss	1.0000
10:125770593:T:C	acceptor_gain	1.0000
10:125773825:TCTTA:T	donor_loss	1.0000
10:125773826:CTTA:C	donor_loss	1.0000
10:125773827:TTA:T	donor_loss	1.0000
10:125773828:TACCT:T	donor_loss	1.0000
10:125773829:ACC:A	donor_loss	1.0000

AlphaMissense

3727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:125773838:A:C	F230L	0.997
10:125773838:A:T	F230L	0.997
10:125773840:A:G	F230L	0.997
10:125773915:A:G	W205R	0.997
10:125773915:A:T	W205R	0.997
10:125772350:G:C	H283D	0.996
10:125772722:G:C	F242L	0.996
10:125772722:G:T	F242L	0.996
10:125772723:A:C	F242C	0.996
10:125772724:A:G	F242L	0.996
10:125772669:A:G	F260S	0.995
10:125773890:A:G	F213S	0.995
10:125773913:C:A	W205C	0.995
10:125773913:C:G	W205C	0.995
10:125773839:A:C	F230C	0.994
10:125772345:T:A	E284D	0.993
10:125772345:T:G	E284D	0.993
10:125772346:T:A	E284V	0.993
10:125772352:A:T	V282D	0.993
10:125772356:C:G	A281P	0.993
10:125772651:A:G	F266S	0.992
10:125772697:G:C	H251D	0.992
10:125773839:A:G	F230S	0.992
10:125772318:G:C	H293Q	0.991
10:125772318:G:T	H293Q	0.991
10:125772336:A:C	H287Q	0.991
10:125772336:A:T	H287Q	0.991
10:125772338:G:C	H287D	0.991
10:125772340:C:T	G286D	0.991
10:125772294:C:A	M301I	0.990

dbSNP variants (sampled 300 via entrez): RS1000529565 (10:125776565 G>A), RS1000826686 (10:125776951 C>A,T), RS1000878981 (10:125776785 T>C), RS1001669636 (10:125767839 G>A,T), RS1001830297 (10:125773495 C>T), RS1002000093 (10:125766301 C>A,G,T), RS1002203966 (10:125774982 G>A,C), RS1002415019 (10:125769713 C>G,T), RS1002453606 (10:125769416 C>T), RS1002565708 (10:125772227 T>G), RS1002633825 (10:125773814 G>A,T), RS1002711601 (10:125775246 T>A), RS1002723302 (10:125769168 G>T), RS1002730672 (10:125768013 G>C), RS1002882850 (10:125774174 C>A,G,T)

Disease associations

OMIM: gene MIM:608416 | disease phenotypes: MIM:616749, MIM:306955

GenCC curated gene-disease

Disease	Classification	Inheritance
heterotaxy, visceral, 7, autosomal	Definitive	Autosomal recessive
situs inversus	Supportive	Autosomal dominant

Mondo (4): heterotaxy, visceral, 7, autosomal (MONDO:0014762), visceral heterotaxy (MONDO:0018677), congenital heart disease (MONDO:0005453), situs inversus (MONDO:0010029)

Orphanet (2): Visceral heterotaxy (Orphanet:450), Situs ambiguus (Orphanet:157769)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_209	Metabolite levels	2.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D012857	Situs Inversus	C16.131.810

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M10: Matrix metallopeptidase

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
aristolochic acid I	increases expression	1
tebuconazole	decreases expression	1
Tetradecanoylphorbol Acetate	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE