MMP26

Summary

MMP26 (matrix metallopeptidase 26, HGNC:14249) is a protein-coding gene on chromosome 11p15.4, encoding Matrix metalloproteinase-26 (Q9NRE1). May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor.

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. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers.

Source: NCBI Gene 56547 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 606 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14249
Approved symbol	MMP26
Name	matrix metallopeptidase 26
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	endometase, MGC126590, MGC126592
Ensembl gene	ENSG00000167346
Ensembl biotype	protein_coding
OMIM	605470
Entrez	56547

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000300762, ENST00000380390, ENST00000690848

RefSeq mRNA: 2 — MANE Select: NM_021801 NM_001384608, NM_021801

CCDS: CCDS7752, CCDS91424

Canonical transcript exons

ENST00000380390 — 8 exons

Exon	Start	End
ENSE00001112210	4989648	4989868
ENSE00001112212	4991371	4991496
ENSE00001112213	4991964	4992125
ENSE00001112215	4990598	4990746
ENSE00001484767	4992214	4992429
ENSE00001484812	4988068	4988310
ENSE00001484815	4767270	4767341
ENSE00003920592	4704784	4705045

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 96.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0446 / max 51.2106, expressed in 6 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112779	0.0306	6
112780	0.0102	3
206169	0.0039	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.91	gold quality
endometrium	UBERON:0001295	77.69	gold quality
tibialis anterior	UBERON:0001385	59.41	silver quality
pancreatic ductal cell	CL:0002079	58.93	silver quality
oviduct epithelium	UBERON:0004804	57.19	silver quality
uterus	UBERON:0000995	55.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.92	gold quality
ileal mucosa	UBERON:0000331	54.14	silver quality
upper leg skin	UBERON:0004262	53.78	silver quality
deltoid	UBERON:0001476	52.47	gold quality
epithelial cell of pancreas	CL:0000083	51.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
quadriceps femoris	UBERON:0001377	49.28	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	45.01
E-ENAD-17	no	47.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CTNNB1, ESR1, JUN, SSRP1, TCF7L2

miRNA regulators (miRDB)

6 targeting MMP26, 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-520F-3P	99.82	71.32	1216
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6080	99.43	69.43	373
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-2909	96.36	67.30	562

Literature-anchored findings (GeneRIF, showing 37)

• role of histidine(81) in mechanism of activation (PMID:11889136)
• Promoter characterization of the novel human matrix metalloproteinase-26 gene: regulation by the T-cell factor-4 implies specific expression of the gene in cancer cells of epithelial origin. (PMID:11931652)
• substrate specificity and protein cleavage sites (PMID:12119297)
• Details of cleavage of pro-MMP-9 by MMP-26, facilitating the efficient cleavage of fibronectin by MMP-9, and promoting invasiveness of ARCaP cells across fibronectin or type IV collagen (PMID:12586837)
• Present throughout menstrual cycle. Elevated during early to mid-luteal phase. Elevations in users of levonorgestrel implants experiencing irregular uterine bleeding. Seems to play role in hormonal regulation and endometrial tissue remodeling. (PMID:12969699)
• distinguish shallow, intermediate, and deep S1’ pocket characteristics (PMID:14532275)
• MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in breast cancer cells. (PMID:14744773)
• Results suggest a functional relationship between TIMP-4 mRNA and MMP-26 mRNA, and possibly a role in human implantation. (PMID:15273280)
• Matrilysin-2 overexpression is associated with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma (PMID:15333466)
• The expression patterns of MMP26 in human placenta suggests complicated roles for MMP26 during the processes of placentation and hematopoiesis (PMID:15601912)
• During esophageal tumorigenesis, MMP-21 and MMP-26 have different, unique expression patterns. (PMID:16641547)
• Maximal expression of MMP-26, in the early and mid-secretory phase suggests its role during implantation and results show it is stored in epithelial cells, is not released spontaneously, and is controlled by TIMP-4 in both stroma and uterine fluid. (PMID:16809379)
• Results indicate that MMP-26 and TIMP-4 may play an integral role during the conversion of high-grade prostatic intraepithelial neoplasia to invasive cancer and may also serve as markers for early prostate cancer diagnosis. (PMID:16940965)
• 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)
• A human breast cancer cell linetransfected with wild-type MMP-26 cDNA showed a calcium-dependent invasive potential when compared with controls. (PMID:17176253)
• The putative role of MMP-26 as a marker of metastasesin pancreatic cancer warrants further studies (PMID:17873896)
• expression of transmembrane 4 superfamily member 4 (TM4SF4) and matrix metalloproteinase 26 (MMP26) was found to be significantly decreased during the implantation window in patients with polycystic ovary syndrome. (PMID:18765015)
• MMP-26 may be served as a tumor marker in monitoring progression and predicting prognosis of non-small cell lung cancer. (PMID:19448419)
• MMP-26 and MMP-9 may contribute to the more aggressive behavior of squamous cell carcinomas in organ transplant recipients (PMID:19674198)
• MMP-26 expression may be associated with multiple human carcinomas. MMP-26 may also contribute to smooth muscle function in the human prostate and cardiovascular system. (PMID:19895737)
• MMP-26 expression in stroma is associated with larger Merkel cell carcinoma with poor prognosis. (PMID:19921252)
• MMP-26 contributes to tumor cell invasion, migration and angiogenesis (PMID:19956866)
• GnRH I and II could up-regulate MMP-26 expression through the JNK signaling pathway in human trophoblast-like/trophoblast cells. (PMID:20074375)
• role of these proteins in the process of invasion and metastasis cannot be ruled out since their presence is more marked along the tumor invasion front compared to more central areas of squamous cell carcinoma of the tongue (PMID:20491537)
• direct association observed between morphological scores of malignancy and MMP immunoreactivity, with the association being significant for MMP-26. present results demonstrate important role of MMPs in development of SCCs of lower lip and tongue. (PMID:21255765)
• MMP-26 plays an important role in local invasion at least in part through coordination with MMP-9. (PMID:21805034)
• Molecular analyses showed significant downregulation of expression of MMP-26 (p=0.03), and significant 9.8-fold upregulation of TGF-beta (p=0.01) in more degenerated discs vs. healthier discs. (PMID:21945733)
• expression of MMP-26 protein was predominantly located in pre- and early-invasive areas suggesting MMP-26 expression as an early event in promoting GM-CSF dependent tumor invasion. (PMID:23634280)
• The MMP-26 promoter region contains a putative ER response element. (PMID:23754174)
• matrilysin-2 was an independent prognostic marker for patients with colorectal cancer (PMID:24318970)
• These results demonstrate that the HOXA10-mediated expression of MMP-26 promotes embryo adhesion during the process of embryonic implantation. (PMID:24565841)
• The binding of MMP-26 to GDF15 was responsible for the processing and maturation of pro-GDF15, and the process was dependent on enzymatic activity of MMP-26. In human placental trophoblast cells, MMP-26 could facilitate the pro-apoptotic effect of GDF15. (PMID:25093616)
• Overexpression of MMP26 in SW1353 cells increased cell invasiveness, while inhibition of MMP26 decreased cell invasiveness. (PMID:25262277)
• We found that only inhibition of JNK significantly decreased the activation of MMP26 in response to FGF1 stimulation, suggesting that activation of FGFR1 signaling may activate JNK to activate MMP26 in non-small-cell lung cancer (PMID:25566961)
• MMP26+CXCR4+ cells may be circulating tumor cells in hepatocellular carcinoma. (PMID:26279442)
• The luciferase report assay demonstrated that MMP26 is a target gene of miR-125b. And the expression profile of MMP26 showed an inverse relationship with miR-125b in vivo and in vitro. (PMID:27143441)
• MMP26 is overexpressed in prostatic neoplasms patients, and can serve as a serum disease biomarker. (PMID:29270749)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp23bb	ENSDARG00000009825
danio_rerio	mmp25b	ENSDARG00000010556
danio_rerio	hpxa	ENSDARG00000012609
danio_rerio	mmp30	ENSDARG00000045887
danio_rerio	mmp25a	ENSDARG00000077290
danio_rerio	mmp13b	ENSDARG00000100794
drosophila_melanogaster	Mmp1	FBGN0035049
caenorhabditis_elegans		WBGENE00006987
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00020646
caenorhabditis_elegans		WBGENE00194737

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), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-26 — Q9NRE1 (reviewed: Q9NRE1)

Alternative names: Endometase, Matrilysin-2

All UniProt accessions (2): A0A8J8YUH5, Q9NRE1

UniProt curated annotations — full annotation on UniProt →

Function. May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor. Is also able to activate progelatinase B.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed specifically in uterus and placenta. Is also widely expressed in malignant tumors from different sources as well as in diverse tumor cell lines.

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 (2): NP_001371537, NP_068573* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001818	Pept_M10_metallopeptidase	Domain
IPR006026	Peptidase_Metallo	Domain
IPR021190	Pept_M10A	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain

Pfam: PF00413

Enzyme classification (BRENDA):

• EC 3.4.24.B7 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (14 total): binding site 4, glycosylation site 2, sequence variant 2, signal peptide 1, propeptide 1, sequence conflict 1, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRE1-F1	79.33	0.58

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): 209

Ligand- & substrate-binding residues (4): 82 (in inhibited form); 208; 212; 218

Glycosylation sites (2): 221, 64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOBP_COLLAGEN_CATABOLIC_PROCESS, GOBP_COLLAGEN_METABOLIC_PROCESS, GOCC_EXTERNAL_ENCAPSULATING_STRUCTURE, ZNF274_TARGET_GENES

GO Biological Process (4): proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), negative regulation of inflammatory response (GO:0050728)

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 (3): obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	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
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP26	HPX	P02790	836
MMP26	TIMP4	Q99727	715
MMP26	TIMP1	P01033	426
MMP26	TIMP3	P35625	401
MMP26	TIMP2	P16035	382
MMP26	MMP24OS	A0A0U1RRL7	349
MMP26	ALB	P02768	344
MMP26	ELN	P15502	320
MMP26	FN1	P02751	308
MMP26	MAGEB10	Q96LZ2	288
MMP26	FURIN	P09958	283
MMP26	LRRC17	Q8N6Y2	264
MMP26	PCSK6	P29122	258
MMP26	VTN	P01141	246
MMP26	MROH7	Q68CQ1	244

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MMP26	SLC25A20	psi-mi:“MI:0914”(association)	0.530
MMP26	NME4	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): MMP26 (Two-hybrid), FECH (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), CNTNAP3B (Affinity Capture-MS), EFR3A (Affinity Capture-MS), GNB2 (Affinity Capture-MS), PTPRK (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), PDF (Affinity Capture-MS), LPHN3 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), EPHA4 (Affinity Capture-MS), UQCC3 (Affinity Capture-MS), NME4 (Affinity Capture-MS)

ESM2 similar proteins: A0A509AST0, A4KX75, B3A0P5, B3A0P7, B5AJT2, G5EDW5, G5EF33, G5EGM1, H2A0L6, H2A0L7, O16977, O35548, O45201, O55761, P12799, P22856, P45442, P51512, P53940, P55114, P55115, P91137, Q06VC5, Q11133, Q20942, Q21179, Q21180, Q21252, Q21388, Q21432, Q25197, Q54BH5, Q54H45, Q54JC9, Q54LH8, Q55CA5, Q5UNW8, Q5UPK9, Q5UQG0, Q5UQZ1

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
MMP26	up-regulates	ECM_disassembly
MMP26	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	548
Likely benign	54
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4852 predictions. Top by Δscore:

Variant	Effect	Δscore
11:4989832:G:GT	donor_gain	1.0000
11:4989845:GAA:G	donor_gain	1.0000
11:4767340:GG:G	donor_gain	0.9900
11:4767341:GG:G	donor_gain	0.9900
11:4842519:G:GT	donor_gain	0.9900
11:4842519:G:T	donor_gain	0.9900
11:4989844:GGAA:G	donor_gain	0.9900
11:4990742:GTGGG:G	donor_gain	0.9900
11:4988251:T:TA	acceptor_gain	0.9800
11:4989847:A:AG	donor_gain	0.9800
11:4991369:A:AG	acceptor_gain	0.9800
11:4991370:G:GG	acceptor_gain	0.9800
11:4802564:A:G	donor_gain	0.9600
11:4904766:G:GT	donor_gain	0.9600
11:4992208:CCATA:C	acceptor_loss	0.9600
11:4992209:CATA:C	acceptor_loss	0.9600
11:4992211:TA:T	acceptor_loss	0.9600
11:4992212:A:C	acceptor_loss	0.9600
11:4992213:G:GA	acceptor_loss	0.9600
11:4882033:G:GG	donor_gain	0.9500
11:4990581:G:C	acceptor_gain	0.9500
11:4991370:GCCC:G	acceptor_gain	0.9500
11:4783555:C:G	donor_gain	0.9400
11:4989839:C:T	donor_gain	0.9400
11:4991482:C:A	donor_gain	0.9400
11:4821499:G:GG	donor_gain	0.9300
11:4896967:T:TA	donor_gain	0.9200
11:4896968:A:AA	donor_gain	0.9200
11:4915609:G:C	donor_gain	0.9200
11:4989835:GAT:G	donor_gain	0.9200

AlphaMissense

1737 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:4990734:T:C	F153L	0.975
11:4990736:C:A	F153L	0.975
11:4990736:C:G	F153L	0.975
11:4991391:T:C	F164L	0.950
11:4991393:T:A	F164L	0.950
11:4991393:T:G	F164L	0.950
11:4991424:T:C	F175L	0.927
11:4991426:T:A	F175L	0.927
11:4991426:T:G	F175L	0.927
11:4990692:T:C	F139L	0.925
11:4990694:C:A	F139L	0.925
11:4990694:C:G	F139L	0.925
11:4991480:G:C	W193C	0.904
11:4991480:G:T	W193C	0.904
11:4990668:T:A	W131R	0.895
11:4990668:T:C	W131R	0.895
11:4990693:T:C	F139S	0.895
11:4989845:G:C	W99C	0.893
11:4989845:G:T	W99C	0.893
11:4992080:T:C	F238L	0.893
11:4992082:C:A	F238L	0.893
11:4992082:C:G	F238L	0.893
11:4991984:G:C	A206P	0.885
11:4991478:T:A	W193R	0.881
11:4991478:T:C	W193R	0.881
11:4990670:G:C	W131C	0.880
11:4990670:G:T	W131C	0.880
11:4992046:G:A	M226I	0.878
11:4992046:G:C	M226I	0.878
11:4992046:G:T	M226I	0.878

dbSNP variants (sampled 300 via entrez): RS1000001542 (11:4744610 C>T), RS1000004189 (11:4801919 A>G), RS1000005288 (11:4963250 G>C,T), RS1000009141 (11:4760668 T>C), RS1000011522 (11:4837686 T>C), RS1000034796 (11:4923187 C>T), RS1000040047 (11:4966668 G>A,C,T), RS1000041870 (11:4879804 A>G), RS1000048069 (11:4729412 A>T), RS1000050956 (11:4918911 A>G), RS1000070909 (11:4877789 T>C,G), RS1000071831 (11:4984867 T>C), RS1000086793 (11:4807329 C>G,T), RS1000094380 (11:4751031 A>C), RS1000110681 (11:4884014 T>C,G)

Disease associations

OMIM: gene MIM:605470 | disease phenotypes: MIM:600057

GenCC curated gene-disease

Mondo (2): myoepithelial tumor (MONDO:0002380), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039)

Orphanet (1): Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003523_16	Coenzyme Q10 levels	2.000000e-06
GCST004335_15	Mean corpuscular volume	9.000000e-11
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007836	coenzyme Q10 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4707 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,512 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL279785	MARIMASTAT	3	29,447
CHEMBL19611	ILOMASTAT	2	12,065

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
ilomastat	Inhibition	7.77	pIC50

ChEMBL bioactivities

15 potent at pChembl≥5 of 16 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.77	IC50	17	nM	ILOMASTAT
7.07	IC50	86	nM	CHEMBL148214
7.01	IC50	97	nM	CHEMBL147882
6.84	IC50	146	nM	CHEMBL148171
6.31	IC50	492	nM	CHEMBL148406
6.13	IC50	744	nM	CHEMBL358539
6.10	IC50	791	nM	CHEMBL147489
6.07	IC50	858	nM	CHEMBL146289
5.84	IC50	1453	nM	CHEMBL147881
5.69	IC50	2046	nM	CHEMBL146718
5.12	IC50	7508	nM	CHEMBL356124
5.10	IC50	7903	nM	CHEMBL424130
5.00	IC50	1e+04	nM	MARIMASTAT

PubChem BioAssay actives

15 with measured affinity, of 25 total; 13 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
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.0170	uM
N,6-dihydroxy-7-methoxy-2-(4-methoxyphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.0860	uM
N,6-dihydroxy-2-(4-methylphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.0970	uM
2-(benzenesulfonyl)-N,6-dihydroxy-7-methoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.1460	uM
2-(4-aminophenyl)sulfonyl-N,6-dihydroxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.4920	uM
N-hydroxy-2-(4-methoxyphenyl)sulfonyl-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.7440	uM
N,6-dihydroxy-2-(4-nitrophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.7910	uM
2-(benzenesulfonyl)-N,6-dihydroxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	0.8580	uM
2-(benzenesulfonyl)-N-hydroxy-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	1.4530	uM
N-hydroxy-2-(4-methylphenyl)sulfonyl-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	2.0460	uM
N,6-dihydroxy-2-(4-methoxyphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	7.5080	uM
2-(2,5-dichlorophenyl)sulfonyl-N,6-dihydroxy-3,4-dihydro-1H-isoquinoline-1-carboxamide	107348: Inhibition of matrix metalloprotease-26 (MMP-26)	ic50	7.9030	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	1274677: Inhibition of full length human recombinant MMP26 using MCA-Arg-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-Glu-Arg-NH2 as substrate preincubated for 60 mins followed by substrate addition by fluorescence assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, increases mutagenesis, affects methylation	4
Hydrogen Peroxide	affects expression	1
Immunosuppressive Agents	decreases expression	1
Methotrexate	decreases expression	1
Progesterone	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069318	Binding	Inhibition of MMP26	Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis