MMP11

Summary

MMP11 (matrix metallopeptidase 11, HGNC:7157) is a protein-coding gene on chromosome 22q11.23, encoding Stromelysin-3 (P24347). May play an important role in the progression of epithelial malignancies.

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. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP’s, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix.

Source: NCBI Gene 4320 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 102 total
• Druggable target: yes
• MANE Select transcript: NM_005940

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7157
Approved symbol	MMP11
Name	matrix metallopeptidase 11
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099953
Ensembl biotype	protein_coding
OMIM	185261
Entrez	4320

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 6 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000215743, ENST00000428253, ENST00000434318, ENST00000437086, ENST00000460352, ENST00000465385, ENST00000465730, ENST00000477567, ENST00000480185, ENST00000488363, ENST00000489582, ENST00000492464, ENST00000493132, ENST00000872483, ENST00000872484, ENST00000872485, ENST00000872486, ENST00000872487

RefSeq mRNA: 1 — MANE Select: NM_005940 NM_005940

CCDS: CCDS13816

Canonical transcript exons

ENST00000215743 — 8 exons

Exon	Start	End
ENSE00000879475	23772849	23772978
ENSE00003502030	23779187	23779416
ENSE00003510640	23780859	23781100
ENSE00003523555	23781193	23781409
ENSE00003600315	23780582	23780715
ENSE00003636030	23783411	23784316
ENSE00003649425	23780359	23780502
ENSE00003692704	23782226	23782483

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 90.59.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6975 / max 306.9597, expressed in 799 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191319	3.6975	799

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	90.59	gold quality
apex of heart	UBERON:0002098	86.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.55	gold quality
endocervix	UBERON:0000458	84.32	gold quality
right uterine tube	UBERON:0001302	82.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.22	gold quality
smooth muscle tissue	UBERON:0001135	80.94	gold quality
ectocervix	UBERON:0012249	80.07	gold quality
left ovary	UBERON:0002119	79.75	gold quality
cortical plate	UBERON:0005343	79.57	gold quality
gall bladder	UBERON:0002110	78.55	gold quality
right ovary	UBERON:0002118	78.12	gold quality
heart left ventricle	UBERON:0002084	78.00	gold quality
right testis	UBERON:0004534	77.81	gold quality
kidney epithelium	UBERON:0004819	77.76	gold quality
mucosa of transverse colon	UBERON:0004991	77.69	gold quality
cardiac ventricle	UBERON:0002082	77.44	gold quality
embryo	UBERON:0000922	77.25	gold quality
ganglionic eminence	UBERON:0004023	77.25	gold quality
left testis	UBERON:0004533	77.24	gold quality
right coronary artery	UBERON:0001625	77.09	gold quality
body of uterus	UBERON:0009853	76.77	gold quality
uterine cervix	UBERON:0000002	76.62	gold quality
right atrium auricular region	UBERON:0006631	75.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.63	gold quality
testis	UBERON:0000473	74.59	gold quality
heart	UBERON:0000948	74.46	gold quality
left uterine tube	UBERON:0001303	74.30	gold quality
cardiac atrium	UBERON:0002081	74.28	gold quality
metanephros cortex	UBERON:0010533	73.85	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	2351.26
E-HCAD-13	yes	1127.83
E-MTAB-8410	yes	32.55
E-MTAB-10855	yes	29.05
E-HCAD-31	yes	19.64
E-MTAB-6678	yes	16.59
E-MTAB-6142	no	27.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPB, CEBPG, JUN, RARB, RARG, SP1

miRNA regulators (miRDB)

52 targeting MMP11, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 40)

• We found that neither S6K-dependent cell growth nor S6K-Thr-398 phosphorylation was affected in rictor-null mutants. (PMID:17462592)
• REPTOR and REPTOR-BP play critical roles in maintaining energy homeostasis and promoting animal survival upon nutrient restriction (PMID:25920570)
• may play role in meningioma invasiveness (PMID:11857311)
• alternative splicing and promoter usage generates an intracellular stromelysin 3 isoform directly translated as an active matrix metalloproteinase (PMID:12006591)
• Data confirmed stromelysin-3’s contribution to breast cancer progression and its expression was shown to have a direct negative effect on patients’ survival. (PMID:12429794)
• MMP11 may have a role in the pathogenesis of papillary thyroid carcinoma (PMID:12538453)
• Active stromelysin-3 increases breast cancer cell survival in three-dimensional Matrigel culture via activation of p42/p44 MAP-kinase (PMID:12845673)
• ST3 protein was more involved in the pathway of colorectal cancer development in females, distal locations, infiltrative growth patterns and microsatellite stability. (PMID:15459498)
• central role of PKC isoforms and the negative regulatory function of c-Src in the control of ST3 expression (PMID:15509588)
• colony formation of MMP11 deficient cells was dramatically inhibited in soft agar and tumorigenicity was reduced in nude mice, respectively (PMID:15582574)
• cathepsin F, matrix metalloproteinases 11 and 12 are upregulated in cervical cancer (PMID:15989693)
• MMP-11, like an inflammatory mediator, may exert a chemotactic influence on macrophages which aggregate in the mesangium; MMP-11 is not likely to have a parallel mitogenic or antifibrotic effect in diseased glomeruli (PMID:17085465)
• MMP11 (metalloproteinase 11) gene shows increased expression in papillary thyroid cancer. (PMID:17091452)
• proposes that ST-3 induction in tumour fibroblasts leads to the stimulation of the IGF-1R pathway in carcinoma cells, thus enhancing their proliferative capacity (PMID:17233884)
• Primary colorectal cancers and metastatic liver lesions showed highly significant differences in MMP-1, -10, -11, and TIMP-1. (PMID:17543340)
• Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy. (PMID:17980449)
• MMP11 may play an important role in carcinogenesis and has potential implication as a biomarker for the diagnosis and prognosis of human cancers including gastric cancer. (PMID:18172255)
• These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells. (PMID:18208802)
• The expression of stromelysin-3 was closely associated with the invasion and metastasis of laryngeal carcinoma. (PMID:18476627)
• MMP11 exhibits collagenolytic function against collagen VI under malignant conditions. (PMID:18622425)
• MMP-11 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. (PMID:19159011)
• Mutational analysis of the cleavage of the cancer-associated laminin receptor by stromelysin-3 reveals the contribution of flanking sequences to site recognition and cleavage efficiency. (PMID:19212658)
• Our study describes the identification of MMP11 as a novel broadly expressed tumor associated antigen as target candidate for cancer immunotherapy. (PMID:19509157)
• MMP-11 and CK-20 are probable prognostic markers whose expression reflects the stages of tumor differentiation and LNM of breast cancer. (PMID:19914229)
• matrix metalloproteinase 11 is a novel factor in the development and progression of gastric cancer and suggest that matrix metalloproteinase 11 is a marker for advanced gastric cancer. (PMID:20060156)
• High expression of MMP-11 or -13, or cluster thereof, were significantly associated with higher probability of biochemical recurrence in prostate cancer (PMID:20160732)
• the results of this study indicate that MMP11 polymorphism may be associated with Kawasaki disease in the Korean population (PMID:20230842)
• The MMP-11 is up-regulated by Gli1 and mediates the migration and invasion induced by Gli1 in MDA-MB-231. (PMID:21442356)
• Serum levels in Chinese patients with advanced gastric carcinoma are not associated with the response to chemotherapy, but play role in lymph node metastasis and prognosis (PMID:21513571)
• MMP-11 is overexpressed in many lobular carcinoma cells, and it may play role in lobular carcinogenesis through increasing resistance to anoikis. (PMID:21773755)
• Report MMP11/12 expression in cervical scrapes cells from cervical precursor lesions. (PMID:22076168)
• Results describe MMP-11 expression in human epithelial colon adenocarcinoma cell lines (Caco-2, HT-29 and BCS-TC2). (PMID:22227581)
• Between two of the tested metalloproteinases (MMP-2 and MMP-11) only MMP-2 appears to have prognostic significance in early forms of breast cancer, and its strong expression is associated with shorter survival. (PMID:22286800)
• expression by fibroblasts associated with poor prognosis in colorectal cancer (PMID:22488635)
• MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF-A. (PMID:22768249)
• Data suggest that intra- and extracellular tracking of MMP-11-overexpressing cancer cells might contribute to the understanding of the activation pathways leading to MMP-11-mediated invasive processes. (PMID:22927434)
• MMP-11 expression was significantly related to clinicopathological parameters, which may be essential to the prediction of disease outcome in patients with invasive ductal carcinoma of the breast. (PMID:23115007)
• Findings define a regulatory role of miR-98 in tumor angiogenesis and invasion through repressed ALK4 and MMP11 expression. (PMID:23211491)
• Knockdown of MMP11 expression could inhibit the proliferation and invasion of gastric adenocarcinoma cells probably through down-regulation of the IGF-1 signaling pathway. (PMID:23755751)
• These findings further suggest MMP11 as a promising biomarker for breast and prostate cabcer. (PMID:24564996)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp11b	ENSDARG00000016718
danio_rerio	mmp11a	ENSDARG00000026325
mus_musculus	Mmp11	ENSMUSG00000000901
rattus_norvegicus	Mmp11	ENSRNOG00000028344
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Stromelysin-3 — P24347 (reviewed: P24347)

Alternative names: Matrix metalloproteinase-11

All UniProt accessions (3): E9PED7, P24347, H7C3I7

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in the progression of epithelial malignancies.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Specifically expressed in stromal cells of breast carcinomas.

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

Cofactor. Binds 1 Ca(2+) ion per subunit. Binds 2 Zn(2+) ions 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_005931* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR006026	Peptidase_Metallo	Domain
IPR018486	Hemopexin_CS	Conserved_site
IPR018487	Hemopexin-like_repeat	Repeat
IPR021158	Pept_M10A_Zn_BS	Binding_site
IPR021190	Pept_M10A	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413

Enzyme classification (BRENDA):

• EC 3.4.24.B3 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (29 total): binding site 11, sequence variant 6, repeat 4, signal peptide 1, propeptide 1, active site 1, chain 1, disulfide bond 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24347-F1	78.07	0.48

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): 216

Ligand- & substrate-binding residues (11): 80 (in inhibited form); 166; 171; 172; 174; 176; 179; 192; 215; 219; 225

Disulfide bonds (1): 294–480

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 204 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, MODULE_172, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, CHIBA_RESPONSE_TO_TSA_UP, PAX4_01, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, ATACCTC_MIR202, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, YOKOE_CANCER_TESTIS_ANTIGENS, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION, FREAC3_01, MODULE_210, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_LOBULAR_NORMAL_DN

GO Biological Process (7): proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), collagen fibril organization (GO:0030199), collagen catabolic process (GO:0030574), negative regulation of fat cell differentiation (GO:0045599), basement membrane organization (GO:0071711)

GO Molecular Function (7): metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), 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 (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular matrix organization	3
endopeptidase activity	2
protein metabolic process	1
cellular component disassembly	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
metallopeptidase activity	1
serine-type peptidase 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
Golgi apparatus	1
intracellular organelle lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP11	SDCBP	O00560	814
MMP11	DENND2B	P78523	772
MMP11	CRYBG1	Q9Y4K1	764
MMP11	MMP10	P09238	728
MMP11	COL10A1	Q03692	618
MMP11	COL11A1	P12107	617
MMP11	COL1A1	P02452	599
MMP11	FURIN	P09958	590
MMP11	FN1	P02751	579
MMP11	SCUBE2	Q9NQ36	578
MMP11	TIMP1	P01033	566
MMP11	TIMP2	P16035	565
MMP11	CTSV	O60911	554
MMP11	THBS2	P35442	533
MMP11	TIMP3	P35625	519

IntAct

0 interactions, top by confidence:

BioGRID (10): MMP25 (Negative Genetic), MMP24 (Negative Genetic), MMP9 (Negative Genetic), MMP16 (Negative Genetic), MMP11 (Negative Genetic), MMP13 (Negative Genetic), MMP8 (Negative Genetic), MMP11 (Affinity Capture-MS), MMP11 (Protein-peptide), MMP11 (Affinity Capture-MS)

ESM2 similar proteins: A6NE02, A8MY62, A8T672, A8T677, A8T695, C9JR72, D3Z7H8, O08644, O15197, O19179, O62763, O94766, P0C0K6, P0C0K7, P21836, P22303, P24347, P35475, P50427, P51839, P51840, P52785, P54760, P55203, Q01634, Q02846, Q04912, Q29499, Q2KHV9, Q2T9T9, Q3UH93, Q5JZY3, Q69ZQ1, Q6NSJ0, Q6ZPS2, Q80W65, Q8BH02, Q8BYG9, Q8CG64, Q8IUL8

Diamond homologs: D0EM77, G5EBU3, O04529, O13065, O18733, O18767, O18927, O23507, O35548, O44836, O54732, O55123, O55761, O60882, O62806, O70138, O75900, O77656, O88272, O88676, O88766, O93470, P03956, P03957, P07152, P08253, P08254, P09237, P09238, P13943, P14780, P21692, P22757, P22894, P23097, P24347, P28053, P28862, P28863, P29136

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MMP11	up-regulates	ECM_disassembly
MMP11	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1879 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23772975:GCCG:G	donor_gain	1.0000
22:23780686:A:G	donor_gain	1.0000
22:23780706:G:T	donor_gain	1.0000
22:23780714:GG:G	donor_gain	1.0000
22:23780715:GG:G	donor_gain	1.0000
22:23781191:A:AG	acceptor_gain	1.0000
22:23781192:G:GC	acceptor_gain	1.0000
22:23781192:GCC:G	acceptor_gain	1.0000
22:23781192:GCCA:G	acceptor_gain	1.0000
22:23781406:CAAGG:C	donor_loss	1.0000
22:23781408:AGGTG:A	donor_loss	1.0000
22:23781409:GGTG:G	donor_loss	1.0000
22:23781410:G:C	donor_loss	1.0000
22:23782474:G:GT	donor_gain	1.0000
22:23772976:CCGGT:C	donor_loss	0.9900
22:23772977:CGG:C	donor_loss	0.9900
22:23772978:GGTG:G	donor_loss	0.9900
22:23772979:G:GG	donor_gain	0.9900
22:23772980:TGAG:T	donor_loss	0.9900
22:23772981:GA:G	donor_loss	0.9900
22:23780576:CTGTA:C	acceptor_loss	0.9900
22:23780577:TGTAG:T	acceptor_loss	0.9900
22:23780578:GTA:G	acceptor_loss	0.9900
22:23780579:TA:T	acceptor_loss	0.9900
22:23780696:G:GT	donor_gain	0.9900
22:23780706:G:GT	donor_gain	0.9900
22:23780713:AGG:A	donor_loss	0.9900
22:23780714:GGGTA:G	donor_loss	0.9900
22:23780716:GTAT:G	donor_loss	0.9900
22:23780717:T:G	donor_loss	0.9900

AlphaMissense

3179 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23782437:G:C	W429C	0.995
22:23782437:G:T	W429C	0.995
22:23780495:T:C	F159L	0.991
22:23780497:C:A	F159L	0.991
22:23780497:C:G	F159L	0.991
22:23780429:T:A	W137R	0.989
22:23780429:T:C	W137R	0.989
22:23780607:T:C	F170L	0.989
22:23780609:T:A	F170L	0.989
22:23780609:T:G	F170L	0.989
22:23780640:T:C	F181L	0.989
22:23780642:C:A	F181L	0.989
22:23780642:C:G	F181L	0.989
22:23780694:T:A	W199R	0.988
22:23780694:T:C	W199R	0.988
22:23780696:G:C	W199C	0.987
22:23780696:G:T	W199C	0.987
22:23780677:T:C	F193S	0.985
22:23781342:G:C	W336C	0.985
22:23781342:G:T	W336C	0.985
22:23782435:T:A	W429R	0.985
22:23782435:T:C	W429R	0.985
22:23783423:T:C	F449S	0.985
22:23783440:T:G	Y455D	0.985
22:23779412:T:G	Y112D	0.984
22:23780431:G:C	W137C	0.984
22:23780431:G:T	W137C	0.984
22:23780496:T:G	F159C	0.980
22:23779370:T:C	F98L	0.979
22:23779372:C:A	F98L	0.979

dbSNP variants (sampled 300 via entrez): RS1000194693 (22:23777549 A>AGAGC), RS1000210893 (22:23780767 A>G,T), RS1000885618 (22:23772748 C>A,G,T), RS1001071597 (22:23771682 C>T), RS1001173025 (22:23779781 A>G), RS1001518356 (22:23784002 A>G), RS1001570865 (22:23784283 A>T), RS1001736254 (22:23774501 G>A), RS1001779561 (22:23778386 G>A), RS1001885508 (22:23771094 G>A), RS1002325470 (22:23771409 C>G,T), RS1002531771 (22:23781422 T>G), RS1002647912 (22:23781646 T>C), RS1002679832 (22:23776356 A>G), RS1002909751 (22:23773144 CA>C)

Disease associations

OMIM: gene MIM:185261 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012099_25	Hypertrophic cardiomyopathy (sarcomere negative)	2.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2867 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 10 [PMID: 18790648]	Inhibition	6.64	pKi

ChEMBL bioactivities

5 potent at pChembl≥5 of 6 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.64	Ki	0.23	nM	CHEMBL447457
8.30	Ki	5	nM	CHEMBL2153737
8.30	Ki	5	nM	CHEMBL115774
6.39	Ki	410	nM	CHEMBL2153738
5.30	IC50	5000	nM	GRASSYSTATIN A

PubChem BioAssay actives

5 with measured affinity, of 16 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(2S)-3-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-[(2-methoxyphenyl)sulfanylmethyl]-3-oxopropyl]-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid	349384: Inhibition of MMP11	ki	0.0002	uM
[2-[[1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-5-phenylpentyl]-[2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid	259192: Binding affinity to MMP11	ki	0.0050	uM
[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-4-phenylbutyl]-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid	689972: Inhibition of MMP-11	ki	0.0050	uM
[(2S)-3-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-oxo-2-[2-(trifluoromethoxy)phenyl]sulfanylpropyl]-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid	689972: Inhibition of MMP-11	ki	0.4100	uM
methyl (2S)-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-2-[[(3S,4S)-4-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[(2S)-2-[(2S)-2-(dimethylamino)-3-methylbutanoyl]oxy-3-methylbutanoyl]oxy-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxy-6-methylheptanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]-methylamino]-3-phenylpropanoyl]pyrrolidine-2-carboxylate	448899: Inhibition of MMP11 catalytic domain after 10 to 15 mins by fluorescence assay	ic50	5.0000	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression	6
Estradiol	increases expression, decreases reaction, affects cotreatment, decreases expression	5
Progesterone	affects cotreatment, decreases expression, increases expression, decreases reaction	5
Benzo(a)pyrene	affects methylation, decreases expression	4
Cadmium	decreases expression, increases abundance	2
Tretinoin	increases expression	2
bisphenol F	increases expression, affects cotreatment	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
periodate-oxidized adenosine	affects expression	1
aflatoxin B2	increases methylation	1
benazol P	affects expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cirsimarin	decreases expression	1
(4-(4-hydroxy-3-isopropyl-5-(4-nitrophenylethynyl)benzyl)-3,5-dimethylphenoxy)acetic acid	decreases reaction, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
SJ 000311413	decreases reaction, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaldehyde	increases expression, increases reaction	1
Camptothecin	increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Dexamethasone	increases expression, affects cotreatment, decreases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002954	Binding	Inhibition of MMP11	Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9KH	Ubigene HEK293 MMP11 KO	Transformed cell line	Female
CVCL_SY58	HAP1 MMP11 (-) 1	Cancer cell line	Male
CVCL_SY59	HAP1 MMP11 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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