MMP10

Summary

MMP10 (matrix metallopeptidase 10, HGNC:7156) is a protein-coding gene on chromosome 11q22.2, encoding Stromelysin-2 (P09238). Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V.

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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 protease. This secreted protease breaks down fibronectin, laminin, elastin, proteoglycan core protein, gelatins, and several types of collagen. The gene is part of a cluster of MMP genes on chromosome 11.

Source: NCBI Gene 4319 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 92 total — 1 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7156
Approved symbol	MMP10
Name	matrix metallopeptidase 10
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166670
Ensembl biotype	protein_coding
OMIM	185260
Entrez	4319

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000279441, ENST00000539681

RefSeq mRNA: 1 — MANE Select: NM_002425 NM_002425

CCDS: CCDS8321

Canonical transcript exons

ENST00000279441 — 10 exons

Exon	Start	End
ENSE00000993181	102772012	102772115
ENSE00000993192	102778624	102778749
ENSE00000993200	102779504	102779745
ENSE00000993208	102770502	102770893
ENSE00000993209	102775188	102775321
ENSE00000993214	102780487	102780628
ENSE00000993219	102776280	102776424
ENSE00002472195	102779213	102779361
ENSE00002482072	102772847	102773006
ENSE00002498265	102776612	102776776

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 98.47.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9263 / max 2611.7244, expressed in 411 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121988	5.9263	411

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	98.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.23	gold quality
palpebral conjunctiva	UBERON:0001812	97.48	gold quality
nasal cavity epithelium	UBERON:0005384	94.48	gold quality
cartilage tissue	UBERON:0002418	94.05	gold quality
nasal cavity mucosa	UBERON:0001826	90.84	gold quality
islet of Langerhans	UBERON:0000006	87.86	gold quality
epithelium of nasopharynx	UBERON:0001951	80.88	gold quality
stromal cell of endometrium	CL:0002255	80.40	gold quality
epithelial cell of pancreas	CL:0000083	76.22	gold quality
decidua	UBERON:0002450	73.51	gold quality
calcaneal tendon	UBERON:0003701	73.39	gold quality
pancreatic ductal cell	CL:0002079	69.76	silver quality
vermiform appendix	UBERON:0001154	69.67	gold quality
amniotic fluid	UBERON:0000173	69.62	gold quality
epithelium of bronchus	UBERON:0002031	69.56	gold quality
bronchus	UBERON:0002185	69.45	gold quality
periodontal ligament	UBERON:0008266	66.68	silver quality
caecum	UBERON:0001153	64.98	gold quality
bronchial epithelial cell	CL:0002328	64.15	gold quality
endometrium epithelium	UBERON:0004811	64.04	gold quality
trachea	UBERON:0003126	62.24	gold quality
tendon	UBERON:0000043	61.92	gold quality
gall bladder	UBERON:0002110	61.11	gold quality
mucosa of urinary bladder	UBERON:0001259	60.05	gold quality
minor salivary gland	UBERON:0001830	57.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.87	gold quality
pancreas	UBERON:0001264	56.79	gold quality
mouth mucosa	UBERON:0003729	55.64	gold quality
gingival epithelium	UBERON:0001949	55.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	2135.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, CEBPB, CTCF, ELK3, ETS1, FOXO1, FOXO3, GLI2, HDAC7, HEY2, MEF2A, MYC, NCOA3, NFKB, SSRP1, STAT3, USP6, ZNF267, ZNF362

miRNA regulators (miRDB)

31 targeting MMP10, 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-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-496	98.66	69.80	931
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-4722-5P	98.46	66.34	1611

Literature-anchored findings (GeneRIF, showing 40)

• The catalytic domain of human matrix metalloproteinase-10 (MMP-10) has been expressed in Escherichia coli and its crystal structure solved at 2.1 angstroms resolution. (PMID:15095982)
• Beta-carotene suppresses UVA-induction of MMP-10. (PMID:15288123)
• a tightly regulated expression level of stromelysin-2 is required for limited matrix degradation at the wound site (PMID:15371548)
• Overexpression of MMP-10 is associated with non-small cell lung cancer (PMID:15375490)
• identified significant interactions between MMP10 (nt+180) polymorphisms and gender in abdominal aortic aneurysm (PMID:15944607)
• zinc finger protein 267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis (PMID:16054593)
• Increased levels of MMP-10 is associated with gastric cancer (PMID:16331256)
• Finally, we found that induction of mmp-3 and mmp-10 gene expression by hypomethylation was cell-specific, suggesting that epigenetic changes may predispose cells to express stromelysin genes. (PMID:16516860)
• C-reactive protein augmented MMP-1 and -10 messenger ribonucleic acid expression in vascular endothelial cells. Might provide a link between inflammation and plaque vulnerability. (PMID:16580524)
• The ability of MMP-10 to superactivate procollagenases that are relevant to cartilage degradation suggests that this activation represents an important mechanism by which this MMP contributes to tissue destruction in arthritis. (PMID:17009259)
• Primary colorectal cancers and metastatic liver lesions showed highly significant differences in MMP-1, -10, -11, and TIMP-1. (PMID:17543340)
• MMP-10 protein levels were higher in the lung tumor tissues than in the adjacent normal tissues. (PMID:17695449)
• Knockdown of MMP-10 expression blocks anchorage-independent growth and invasion of NSCLC cells and addition of catalytically active MMP-10 to PKCiota- or Par6alpha-deficient cells restores anchorage-independent growth and invasion (PMID:18427549)
• VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating MT-MMP1/MMP10 expression and angiogenesis. (PMID:18617643)
• Study showed that MMP-9 and TIMP-2 were highly produced in brain microvessels while MMP-10 was notably increased in neurons of the ischemic brain but not in healthy areas. (PMID:19317417)
• MMP1 and MMP10 were suitable markers for cancer detection with gingiva and margin as controls. Using neck tissue as the control, only MMP10 was suitable for cancer detection (PMID:19489686)
• Results suggest that MMP-10 may be important in the initial stages of squamous cell cancer progression and induced in the stroma relating to the general host-response reaction to skin cancer. (PMID:19601983)
• MMP-10 expression is increased in the symptomatic degenerate intervertebral disc (PMID:19695094)
• circulating MMP-10 levels (P<0.01) were augmented in patients with endothelial activation associated with high (disseminated intravascular coagulation) and moderate (previous acute myocardial infarction) systemic thrombin generation (PMID:19762781)
• MMP-10 and MMP-26, in particular, may associate with aggressive Merkel cell carcinoma. (PMID:19921252)
• TGF-beta transcriptionally upregulated MMP-10 through activation of MEF2A, concomitant with acetylation of core histones increasing around the promoter, as a consequence of degradation of the class IIa HDACs. (PMID:19935709)
• changes in the extracellular matrix metabolism during the ageing process influence the level of circulating MMP-3 and MMP-10, as well as their tissue inhibitors TIMP-1 and TIMP-2, in a healthy population (PMID:20215736)
• MMP-10 and -7 abundance increased, accompanied by decreased TIMP-4 in dilated cardiomyopathy failing hearts compared with non-failing hearts. (PMID:20219015)
• Data demonstrate induction of MMP-10 by VEGF in HUVEC and support an angiogenic role for MMP-10 in response to VEGF stimulation in vitro and in vivo. (PMID:20432469)
• Enhanced expression of MMP-10 is associated with progression from non-dysplastic Barrett’s oesophagus to adenocarcinoma. (PMID:20584750)
• Immunocytochemistry also revealed protein expression for MMP-2, 3, 8, 9 and 10 in cultured HUVEC. (PMID:20936527)
• No association was found between MMP10 C/T rs486055 variants and anterior cruciate ligament rupture. (PMID:21410539)
• genetic variations are associated with increased risk of ulcerative colitis in Caucasians of New Zealand (PMID:21925226)
• the roles of MMP-10 in the invasion of head and neck squamous cell carcinoma cells in vitro (PMID:21998657)
• Mmp10 is overexpressed in lung tumors induced by either the smoke carcinogen urethane or oncogenic Kras. (PMID:22022614)
• MMP-10 was capable of enhancing tissue plasminogen activator-induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation-mediated mechanism. (PMID:22104553)
• Findings suggest that MMP10 plays an important role in esophageal squamous cell carcinoma progression in the early stage, and overexpression of MMP10 in tumor tissues could be used as a potential prognostic marker in the early clinical stage of ESCC. (PMID:22121946)
• Data show that TIMP-1 inhibits the MMP-10 with a K(i) of 1.1 x 10(-9) M, and TIMP-2 inhibits the MMP-10 with a K(i) of 5.8 x 10(-9) M. (PMID:22427646)
• Thrombin/CD40L elicited a strong synergistic effect on endothelial MMP-10 expression and microparticles containing MMP-10 in vitro and in vivo, which may represent a new link between inflammation/thrombosis with prognostic implications. (PMID:22492089)
• High MMP-10 is associated with malignant pleural effusion. (PMID:22524815)
• Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. (PMID:22545096)
• COOH truncation of the hepatitis B virus X protein, plays a role in enhancing cell invasiveness and metastasis in hepatocellular carcinoma by activating MMP10 through C-Jun. (PMID:22821423)
• Variants in MMP1 through MMP10 and MMP2 regions seem to affect population variation in ocular refraction in environmental conditions less favorable for myopia development. (PMID:23098370)
• serum proMMP-10 after acute ischemic stroke is associated with TNFalpha and may have a role in brain damage and poor outcome (PMID:23742289)
• Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells. (PMID:24009192)

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), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Stromelysin-2 — P09238 (reviewed: P09238)

Alternative names: Matrix metalloproteinase-10, Transin-2

All UniProt accessions (2): P09238, F5GYX7

UniProt curated annotations — full annotation on UniProt →

Function. Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V. Activates procollagenase.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Cofactor. 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_002416* (*=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
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
IPR036365	PGBD-like_sf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily

Pfam: PF00045, PF00413, PF01471

Enzyme classification (BRENDA):

• EC 3.4.24.22 — stromelysin 2 (BRENDA: 3 organisms, 37 substrates, 21 inhibitors, 2 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(7-METHOXYCOUMARIN-4-YL)ACETYL-ARG-PRO-LYS-PRO-V	0.023	1

UniProt features (42 total): strand 11, binding site 8, sequence variant 8, helix 4, repeat 4, signal peptide 1, propeptide 1, disulfide bond 1, chain 1, turn 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9CSX	X-RAY DIFFRACTION	1.67
3V96	X-RAY DIFFRACTION	1.9
1Q3A	X-RAY DIFFRACTION	2.1
4ILW	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09238-F1	86.55	0.63

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): 218

Ligand- & substrate-binding residues (8): 167; 169; 182; 195; 217; 221; 227; 91 (in inhibited form)

Disulfide bonds (1): 289–476

Function

Pathways and Gene Ontology

Reactome pathways

5 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-5687128	MAPK6/MAPK4 signaling
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 195 (showing top): LI_CISPLATIN_RESISTANCE_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, chr11q22, DAZARD_UV_RESPONSE_CLUSTER_G4, ONDER_CDH1_TARGETS_3_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, FREDERICK_PRKCI_TARGETS, MODULE_210, HUPER_BREAST_BASAL_VS_LUMINAL_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, TATA_C

GO Biological Process (4): proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574)

GO Molecular Function (8): metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), zinc ion binding (GO:0008270), endopeptidase activity (GO:0004175), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Extracellular matrix organization	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endopeptidase activity	2
peptidase activity	2
protein metabolic process	1
cellular component disassembly	1
extracellular matrix organization	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
metallopeptidase activity	1
serine-type peptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP10	SNRPA	P09012	892
MMP10	FN1	P02751	844
MMP10	TIMP1	P01033	839
MMP10	HDAC7	Q8WUI4	803
MMP10	TIMP2	P16035	791
MMP10	MMP11	P24347	728
MMP10	EPHA2	P29317	692
MMP10	ELN	P15502	660
MMP10	MMP7	P09237	653
MMP10	SERPINE1	P05121	646
MMP10	COL7A1	Q02388	633
MMP10	CXCL8	P10145	624
MMP10	TIMP4	Q99727	613
MMP10	EFNA1	P20827	602
MMP10	TIMP3	P35625	593

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MMP10	TIMP1	psi-mi:“MI:0914”(association)	0.530
MMP3	APOE	psi-mi:“MI:0914”(association)	0.530
MMP3	MMP10	psi-mi:“MI:0914”(association)	0.530
MAPT	LANCL1	psi-mi:“MI:0914”(association)	0.350
MMP10	HS3ST1	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): MMP10 (Affinity Capture-MS), MMP10 (Affinity Capture-MS), GAL (Affinity Capture-MS), PCSK1N (Affinity Capture-MS), APOE (Affinity Capture-MS), TIMP1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), MAN1A1 (Affinity Capture-MS), EMILIN3 (Affinity Capture-MS), NUCB1 (Affinity Capture-MS), TNFSF9 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), MMP10 (Affinity Capture-MS)

ESM2 similar proteins: F1RWC3, F7A4A7, O02668, O08523, O18733, O55123, O60494, O70244, O75443, O88923, P03957, P07152, P08253, P08254, P09238, P14780, P28862, P28863, P33434, P33436, P50757, P52176, P56677, P57999, P97435, P98072, P98073, P98074, P98092, Q0IIH7, Q29RU2, Q2PC93, Q3ZCN5, Q5ZQU0, Q62635, Q6V0K7, Q6ZRI0, Q70E20, Q8BG22, Q8R4U0

Diamond homologs: A4KX75, D0EM77, G5EBU3, O04529, O18733, O18767, O18927, O23507, O55123, O55761, O60882, O62806, O77656, P03956, P03957, P07152, P08253, P08254, P09237, P09238, P13943, P14780, P21692, P22757, P23097, P28862, P28863, P29136, P33434, P33435, P33436, P34960, P39900, P41245, P41246, P45452, P50280, P50281, P50282, P50757

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
USP6	“up-regulates quantity by expression”	MMP10	“transcriptional regulation”
“Vincristine sulfate”	“down-regulates activity”	MMP10	“chemical inhibition”
ZNF267	“down-regulates quantity by repression”	MMP10	“transcriptional regulation”
WNT7A	“up-regulates quantity by expression”	MMP10	“transcriptional regulation”
MMP10	“down-regulates quantity by destabilization”	HAPLN1	cleavage
MMP10	up-regulates	ECM_disassembly
MMP10	down-regulates	ECM
FOXC1	“up-regulates quantity by expression”	MMP10	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	74
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1455268	NC_000011.9:g.(?101323686)(103349981_?)del	Pathogenic

SpliceAI

745 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102772006:TCTTA:T	donor_loss	1.0000
11:102772007:CTTAC:C	donor_loss	1.0000
11:102772008:TTA:T	donor_loss	1.0000
11:102772009:TACCA:T	donor_loss	1.0000
11:102772010:A:AC	donor_gain	1.0000
11:102772011:C:A	donor_loss	1.0000
11:102772011:C:CC	donor_gain	1.0000
11:102772014:AATG:A	donor_gain	1.0000
11:102772111:CAAAT:C	acceptor_gain	1.0000
11:102772113:AAT:A	acceptor_gain	1.0000
11:102772115:TC:T	acceptor_loss	1.0000
11:102772116:C:CA	acceptor_loss	1.0000
11:102772116:C:CC	acceptor_gain	1.0000
11:102772117:T:A	acceptor_loss	1.0000
11:102772122:C:CT	acceptor_gain	1.0000
11:102772841:TCTCA:T	donor_loss	1.0000
11:102772842:CTCA:C	donor_loss	1.0000
11:102772843:TCACC:T	donor_loss	1.0000
11:102772844:CA:C	donor_loss	1.0000
11:102772845:ACCT:A	donor_gain	1.0000
11:102772846:C:CG	donor_loss	1.0000
11:102772846:CCT:C	donor_gain	1.0000
11:102772846:CCTC:C	donor_gain	1.0000
11:102772848:T:TA	donor_gain	1.0000
11:102773003:TTTC:T	acceptor_gain	1.0000
11:102773006:CC:C	acceptor_loss	1.0000
11:102773006:CCTAT:C	acceptor_gain	1.0000
11:102773007:C:CA	acceptor_loss	1.0000
11:102773008:T:G	acceptor_loss	1.0000
11:102773010:T:TC	acceptor_gain	1.0000

AlphaMissense

3158 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102779223:A:C	F162L	0.988
11:102779223:A:T	F162L	0.988
11:102779225:A:G	F162L	0.988
11:102779527:C:A	W108C	0.988
11:102779527:C:G	W108C	0.988
11:102779291:A:G	W140R	0.983
11:102779291:A:T	W140R	0.983
11:102779529:A:G	W108R	0.980
11:102779529:A:T	W108R	0.980
11:102772908:C:G	A389P	0.979
11:102776323:C:G	A297P	0.978
11:102778640:C:A	W202C	0.978
11:102778640:C:G	W202C	0.978
11:102778642:A:G	W202R	0.978
11:102778642:A:T	W202R	0.978
11:102779289:C:A	W140C	0.978
11:102779289:C:G	W140C	0.978
11:102776315:G:C	S299R	0.977
11:102776315:G:T	S299R	0.977
11:102776317:T:G	S299R	0.977
11:102779650:C:A	Q67H	0.975
11:102779650:C:G	Q67H	0.975
11:102778727:A:C	F173L	0.974
11:102778727:A:T	F173L	0.974
11:102778729:A:G	F173L	0.974
11:102775233:C:G	A341P	0.973
11:102770853:A:C	F457L	0.970
11:102770853:A:T	F457L	0.970
11:102770855:A:G	F457L	0.970
11:102772030:C:G	A438P	0.969

dbSNP variants (sampled 300 via entrez): RS1000374763 (11:102775575 A>G), RS1000427322 (11:102775760 C>T), RS1000581070 (11:102771161 C>A,T), RS1000781216 (11:102774926 T>C), RS1001036545 (11:102771424 T>C), RS1001124672 (11:102776315 G>C), RS1001508289 (11:102782298 C>G), RS1001958822 (11:102782096 G>A), RS1002592698 (11:102773890 C>A,G,T), RS1002686394 (11:102779025 G>A,C,T), RS1002848862 (11:102777365 C>T), RS1003055023 (11:102774125 T>C), RS1003180493 (11:102778533 T>C), RS1003700240 (11:102772207 T>C), RS1004013440 (11:102770671 A>G)

Disease associations

OMIM: gene MIM:185260 | disease phenotypes: MIM:190300, MIM:208500

GenCC curated gene-disease

Mondo (2): essential tremor (MONDO:0003233), Jeune syndrome (MONDO:0018770)

Orphanet (2): Jeune syndrome (Orphanet:474), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001860_5	Multiple sclerosis	1.000000e-06
GCST001942_2	Prostate cancer	2.000000e-11
GCST006585_2316	Blood protein levels	1.000000e-42
GCST006585_348	Blood protein levels	3.000000e-15
GCST006585_589	Blood protein levels	4.000000e-21

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350
C537571	Jeune syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4270 (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: 30,062 (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
CHEMBL440498	CTS-1027	2	615

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2071230	MMP1, MMP10		0.00	0
rs7945189	MMP1, MMP10		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
CM-352	Inhibition	7.82	pIC50
marimastat	Inhibition	7.16	pIC50
MMP13 tracer [18F]5j	Inhibition	5.51	pIC50

Binding affinities (BindingDB)

70 measured of 112 human assays (112 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(4S)-5-[3-(carboxymethyl)piperidin-1-yl]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	12 nM	US-8691753
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	18.1 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	31 nM	US-8691753
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	39 nM	US-8691753
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]pentanoic acid	KI	39.3 nM	US-8691753
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	45 nM	US-8691753
Inhibitor, 18	KI	47 nM
(4S)-5-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	49 nM	US-8691753
(3S)-4-amino-3-[[(2S)-3-carboxy-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-4-oxobutanoic acid	KI	52 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-carboxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	55 nM	US-8691753
Inhibitor, 17	KI	57 nM
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	65 nM	US-8691753
(4S)-5-[[1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	68 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	73 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	76 nM	US-8691753
(4S)-5-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-oxo-4-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]pentanoic acid	KI	78 nM	US-8691753
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]pentanoic acid	KI	83 nM	US-8691753
(3S)-4-amino-3-[[(2S)-3-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-4-oxobutanoic acid	KI	86 nM	US-8691753
(4S)-5-amino-4-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]-5-oxopentanoic acid	KI	90 nM	US-8691753
(4S)-5-amino-4-[[(2S)-3-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]propanoyl]amino]-5-oxopentanoic acid	KI	91 nM	US-8691753
(3S)-4-amino-4-oxo-3-[[(2S)-2-[3-[3-(4-phenylphenyl)-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]butanoic acid	KI	93 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[4-(5-methylthiophen-2-yl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	97 nM	US-8691753
(4S)-5-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	110 nM	US-8691753
(4R)-5-amino-4-[[(2S)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	112 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-carboxy-1-oxopropan-2-yl]amino]-4-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]-5-oxopentanoic acid	KI	112 nM	US-8691753
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	116 nM	US-8691753
Inhibitor, 16	KI	127 nM
(4S)-5-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	140 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-(4-thiophen-2-ylphenyl)propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	142 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	147 nM	US-8691753
(5S)-6-amino-5-[[(2S)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-6-oxohexanoic acid	KI	150 nM	US-8691753
(4S)-5-amino-4-[[(2S)-2-[3-[4-(1,3-benzothiazol-2-yl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	151 nM	US-8691753
RXP470, Compound 4	KI	192 nM
(4S)-5-[[(2S)-1,5-diamino-1,5-dioxopentan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	204 nM	US-8691753
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-(4-thiophen-3-ylphenyl)propanoylamino]butanoyl]amino]pentanoic acid	KI	225 nM	US-8691753
(4S)-5-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	234 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[4-(5-phenylthiophen-2-yl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	279 nM	US-8691753
(4S)-5-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	298 nM	US-8691753
(2S)-2-[[(2S)-2-[3-(4-phenylphenyl)propanoylamino]butanoyl]amino]butanamide	KI	319 nM	US-8691753
(4S)-5-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	KI	332 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-carboxy-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	334 nM	US-8691753
(4S)-5-[3-(carboxymethyl)anilino]-5-oxo-4-[3-[4-(4-phenylthiophen-2-yl)phenyl]propanoylamino]pentanoic acid	KI	339 nM	US-8691753
(4S)-5-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	348 nM	US-8691753
(4S)-5-[[(2S)-1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxo-4-[3-(4-thiophen-2-ylphenyl)propanoylamino]pentanoic acid	KI	371 nM	US-8691753
(4S)-5-amino-5-oxo-4-[3-[4-(4-phenylthiophen-2-yl)phenyl]propanoylamino]pentanoic acid	KI	377 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	386 nM	US-8691753
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[[(2R)-2-(carboxymethyl)-3-[4-(4-phenylthiophen-2-yl)phenyl]propanoyl]amino]butanoyl]amino]-5-oxopentanoic acid	KI	401 nM	US-8691753
(4S)-5-amino-4-[[(2R)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	KI	403 nM	US-8691753
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-[4-(thiadiazol-4-yl)phenyl]propanoylamino]butanoyl]amino]pentanoic acid	KI	442 nM	US-8691753
(4S)-5-amino-5-oxo-4-[[(2S)-2-[3-(4-phenylphenyl)propanoylamino]butanoyl]amino]pentanoic acid	KI	445 nM	US-8691753

ChEMBL bioactivities

183 potent at pChembl≥5 of 197 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL3932562
9.46	IC50	0.35	nM	CHEMBL3889936
9.27	IC50	0.54	nM	CTS-1027
8.85	Ki	1.4	nM	CHEMBL4096462
8.62	IC50	2.4	nM	CHEMBL3971135
8.59	IC50	2.6	nM	CHEMBL3958969
8.52	IC50	3	nM	CHEMBL3417750
8.40	IC50	4	nM	CHEMBL3417745
8.21	IC50	6.2	nM	CHEMBL3955430
8.15	IC50	7	nM	CHEMBL3417748
8.11	Ki	7.7	nM	CHEMBL3675573
8.11	IC50	7.8	nM	CHEMBL5199189
8.05	IC50	9	nM	CHEMBL3417766
7.92	IC50	12	nM	CHEMBL3417770
7.92	IC50	12	nM	CHEMBL3417742
7.89	IC50	13	nM	CHEMBL3417752
7.89	IC50	13	nM	BAY-7598
7.85	IC50	14	nM	CHEMBL3417755
7.80	IC50	16	nM	CHEMBL3417765
7.77	IC50	17	nM	CHEMBL3417769
7.77	IC50	17	nM	CHEMBL3417764
7.75	IC50	18	nM	CHEMBL3417767
7.68	IC50	21	nM	CHEMBL3417751
7.62	IC50	24	nM	CHEMBL5278446
7.62	IC50	24	nM	CHEMBL5556387
7.53	IC50	29.51	nM	CHEMBL4071820
7.52	IC50	30	nM	CHEMBL4068241
7.51	IC50	31	nM	CHEMBL4071820
7.50	IC50	32	nM	CHEMBL3417746
7.47	IC50	34	nM	CHEMBL3900916
7.46	Ki	35	nM	CHEMBL3675566
7.46	Ki	35	nM	CHEMBL3670695
7.41	Ki	38.8	nM	CHEMBL3675594
7.38	IC50	42	nM	CHEMBL3417749
7.36	Ki	44	nM	CHEMBL3670692
7.35	IC50	44.5	nM	CHEMBL5176328
7.33	Ki	47	nM	CHEMBL1232487
7.32	Ki	48	nM	CHEMBL3670693
7.29	Ki	51	nM	CHEMBL3670698
7.29	IC50	51	nM	CHEMBL5198463
7.28	IC50	53	nM	CHEMBL5562384
7.27	IC50	54	nM	CHEMBL3417760
7.26	IC50	55	nM	CHEMBL4068176
7.21	IC50	62	nM	CHEMBL3417754
7.19	IC50	64	nM	CHEMBL3907007
7.17	IC50	68	nM	CHEMBL3417761
7.16	IC50	69	nM	MARIMASTAT
7.15	Ki	71	nM	CHEMBL3675570
7.12	Ki	76	nM	CHEMBL3675563
7.10	Ki	80	nM	CHEMBL3675605

PubChem BioAssay actives

148 with measured affinity, of 277 total; 50 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
N-[[3-[4-[2-[formyl(hydroxy)amino]-3-methylbutyl]sulfonylphenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0003	uM
N-[[3-[4-[[(2S)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]phenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0003	uM
4-[[4-(4-chlorophenoxy)phenyl]sulfonylmethyl]-N-hydroxyoxane-4-carboxamide	1162790: Inhibition of human recombinant MMP10 using fluorescence peptide Cy3-PLGLK(Cy5Q)AR-NH2 substrate by fluorescence assay	ic50	0.0005	uM
(4S)-5-amino-4-[[(2S)-4-carboxy-2-[[(2R)-2-[[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]methyl]-4-(hydroxyamino)-4-oxobutanoyl]amino]butanoyl]amino]-5-oxopentanoic acid	1460166: Inhibition of human MMP10 catalytic domain using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 fluorogenic substrate by spectrophotometric analysis	ki	0.0014	uM
(2S)-3-methyl-2-[[4-[3-[[(4-oxo-3H-quinazoline-2-carbonyl)amino]methyl]phenyl]phenyl]sulfonylamino]butanoic acid	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0024	uM
N-[[3-[3-[2-(hydroxycarbamoyl)piperidin-1-yl]sulfonylpropoxy]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0026	uM
3-[4-[4-(difluoromethoxy)phenoxy]phenyl]sulfonyl-N-hydroxy-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0030	uM
N-hydroxy-3-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0040	uM
4-oxo-N-[[3-[4-[2-(5-oxo-1,4-dihydro-1,2,4-triazol-3-yl)acetyl]piperazin-1-yl]phenyl]methyl]-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0062	uM
N-hydroxy-3-[4-(4-methylphenoxy)phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0070	uM
N-hydroxy-4-[4-[4-(4-methoxyphenyl)triazol-1-yl]phenyl]sulfonyloxane-4-carboxamide	1863973: Inhibition of MMP-10 (unknown origin)	ic50	0.0078	uM
(4R)-5-amino-4-[[(2S)-2-[[2-[[(4-bromophenyl)-hydroxyphosphoryl]methyl]-3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoic acid	1799769: Enzyme Assay from Article 10.1074/jbc.M112.380782: “Simple Pseudo-dipeptides with a P2’ Glutamate: A NOVEL INHIBITOR FAMILY OF MATRIX METALLOPROTEASES AND OTHER METZINCINS.”	ki	0.0080	uM
8-acetyl-N-hydroxy-3-[4-(4-methoxyphenoxy)phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0090	uM
4-oxo-N-[[3-[4-[2-(5-oxo-1,2-dihydropyrazol-3-yl)acetyl]piperazin-1-yl]phenyl]methyl]-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0100	uM
N-[[3-[4-[2-[carbamoyl(hydroxy)amino]-3-methylbutyl]sulfonylphenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0100	uM
N-[[3-[4-[2-(2,5-dioxoimidazolidin-4-yl)acetyl]piperazin-1-yl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0100	uM
N-hydroxy-3-[4-(4-methoxyphenoxy)phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0120	uM
(3R)-N-hydroxy-3-[4-[4-(methylcarbamoyl)phenoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0120	uM
N-hydroxy-3-[4-[4-(pyrrolidine-1-carbonyl)phenoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0130	uM
N-hydroxy-3-[4-(3-methoxyphenoxy)phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0140	uM
N-hydroxy-3-[4-(4-methoxyphenoxy)phenyl]sulfonyl-8-(3,3,3-trifluoropropyl)-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0160	uM
(3S)-N-hydroxy-3-[4-[4-(methylcarbamoyl)phenoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0170	uM
N-hydroxy-3-[4-(4-methoxyphenoxy)phenyl]sulfonyl-8-methyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0170	uM
[4-[[3-(hydroxycarbamoyl)-8-azaspiro[4.5]decan-3-yl]sulfonyl]phenyl] 4-methoxybenzoate	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0180	uM
N-hydroxy-3-[4-[4-(methylcarbamoyl)phenoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0210	uM
(3S)-1,2-diacetyl-3-(4-bromophenyl)-7-methyl-3H-[1,2,4]triazolo[4,3-a]pyrimidin-5-one	1938638: Inhibition of MMP-10 (unknown origin)	ic50	0.0240	uM
1,2-diacetyl-3-(4-bromophenyl)-7-methyl-8,8a-dihydro-3H-[1,2,4]triazolo[4,3-a]pyrimidin-5-one	2073909: Inhibition of MMP-10 (unknown origin) using 5-FAM-Pro-Leu-OH as substrate by fluorimetric assay	ic50	0.0240	uM
N-[(4-fluoro-3-methoxyphenyl)methyl]-3-[1-[[4-(1,3-oxazol-5-yl)phenyl]methyl]-2,4-dioxopyrimidin-5-yl]prop-2-ynamide	1476191: Inhibition of MMP10 (unknown origin) assessed using (5-FAM/QX) FRET peptide as substrate by fluorescence assay	ic50	0.0295	uM
5-methyl-4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433729: Inhibition of APMA-activated recombinant human MMP-10 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0300	uM
N-hydroxy-3-[4-[[4-(trifluoromethoxy)phenyl]methoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0320	uM
5-(3-chlorophenyl)-4-oxo-N-[[3-[4-[(5-oxo-1,4-dihydro-1,2,4-triazol-3-yl)methylsulfonylmethyl]phenyl]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0340	uM
3-[4-(4-tert-butylphenoxy)phenyl]sulfonyl-N-hydroxy-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0420	uM
4-[4-[4-[4-(dimethylamino)phenyl]triazol-1-yl]phenyl]sulfonyl-N-hydroxyoxane-4-carboxamide	1863973: Inhibition of MMP-10 (unknown origin)	ic50	0.0445	uM
(4S)-5-amino-4-[[(2R)-4-carboxy-2-[3-[3-[4-(3-chlorophenyl)phenyl]-1,2-oxazol-5-yl]propanoylamino]butanoyl]amino]-5-oxopentanoic acid	1863958: Inhibition of human MMP-10 expressed in Escherichia coli BL21(DE3) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 30 mins followed by susbstrate addition by photon-counter spectrophotometer analysis	ki	0.0480	uM
N-hydroxy-4-[4-[4-(4-phenylphenyl)triazol-1-yl]phenyl]sulfonyloxane-4-carboxamide	1863973: Inhibition of MMP-10 (unknown origin)	ic50	0.0510	uM
2-[(2E)-2-[(4-methoxyphenyl)methylidene]hydrazinyl]-4-methyl-1H-pyrimidin-6-one	2073909: Inhibition of MMP-10 (unknown origin) using 5-FAM-Pro-Leu-OH as substrate by fluorimetric assay	ic50	0.0530	uM
N-hydroxy-3-(4-phenylmethoxyphenyl)sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0540	uM
(4S)-5-amino-5-oxo-4-[3-[4-(4-phenylphenyl)phenyl]propanoylamino]pentanoic acid	1799769: Enzyme Assay from Article 10.1074/jbc.M112.380782: “Simple Pseudo-dipeptides with a P2’ Glutamate: A NOVEL INHIBITOR FAMILY OF MATRIX METALLOPROTEASES AND OTHER METZINCINS.”	ki	0.0540	uM
5-(3-fluorophenyl)-4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide	1433729: Inhibition of APMA-activated recombinant human MMP-10 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0550	uM
N-hydroxy-3-[4-[(6-methoxy-3-pyridinyl)oxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0620	uM
N-[[3-[4-[2-[acetyl(hydroxy)amino]-3-methylbutyl]sulfonylphenyl]phenyl]methyl]-4-oxo-3H-quinazoline-2-carboxamide	1328781: Inhibition of recombinant human AMPA-activated MMP10 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.0640	uM
N-hydroxy-3-[4-[[4-(methylcarbamoyl)phenyl]methoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0680	uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	1989135: Inhibition of human recombinant MMP-10 using Mca-Aug-Pro-Lys-Pro-Val-Glu-Nval-Trp-Arg-Lys(Dnp)-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence based analysis	ic50	0.0690	uM
N-hydroxy-3-(4-methoxyphenyl)sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0840	uM
N-hydroxy-3-[4-[3-(methylcarbamoyl)phenoxy]phenyl]sulfonyl-8-azaspiro[4.5]decane-3-carboxamide	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.0890	uM
(3R,4R)-N-hydroxy-4-[[4-[(2-methylquinolin-4-yl)methoxy]benzoyl]amino]oxane-3-carboxamide	313567: Inhibition of MMP10	ki	0.1000	uM
[4-[[3-(hydroxycarbamoyl)-8-azaspiro[4.5]decan-3-yl]sulfonyl]phenyl] 4-(methylcarbamoyl)benzoate	1200506: Inhibition of MMP-10 (unknown origin) measured every minute for 1 hr by fluorescence assay	ic50	0.1030	uM
3-[1-[[4-(cyclopropylsulfamoyl)phenyl]methyl]-2,4-dioxopyrimidin-5-yl]-N-[(4-fluoro-3-methoxyphenyl)methyl]prop-2-ynamide	1476191: Inhibition of MMP10 (unknown origin) assessed using (5-FAM/QX) FRET peptide as substrate by fluorescence assay	ic50	0.1100	uM
3-[1-[[4-(tert-butylsulfamoyl)phenyl]methyl]-2,4-dioxopyrimidin-5-yl]-N-[(4-fluoro-3-methoxyphenyl)methyl]prop-2-ynamide	1476191: Inhibition of MMP10 (unknown origin) assessed using (5-FAM/QX) FRET peptide as substrate by fluorescence assay	ic50	0.1310	uM
4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-ylsulfanyl)ethoxy]phenyl]methyl]-3H-quinazoline-2-carboxamide	1433729: Inhibition of APMA-activated recombinant human MMP-10 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	ic50	0.1400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression, decreases secretion	8
sodium arsenite	decreases expression, increases expression	3
Acetaminophen	affects cotreatment, increases expression	3
Aerosols	decreases secretion, increases expression	3
Cannabidiol	increases expression, affects cotreatment, decreases expression	3
Copper	decreases expression, increases expression, affects binding	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Ethinyl Estradiol	affects expression, decreases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
2-methyl-4-isothiazolin-3-one	increases expression	2
chloropicrin	increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Lipopolysaccharides	increases expression, affects response to substance	2
Methotrexate	decreases expression, increases expression	2
Nickel	increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Quercetin	decreases expression, increases expression	2
Silicon Dioxide	increases expression	2
Sodium Dodecyl Sulfate	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases expression	2
4-oxoretinoic acid	decreases expression	1
urushiol	increases expression	1
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects expression	1
citral	affects expression	1
titanium dioxide	increases expression	1

ChEMBL screening assays

52 unique, capped per target: 48 binding, 3 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005437	Binding	Inhibition of MMP10	Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. — Bioorg Med Chem
CHEMBL4000927	ADMET	Inhibition of APMA-activated recombinant human MMP-10 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method	Discovery of Novel, Highly Potent, and Selective Matrix Metalloproteinase (MMP)-13 Inhibitors with a 1,2,4-Triazol-3-yl Moiety as a Zinc Binding Group Using a Structure-Based Design Approach. — J Med Chem
CHEMBL813244	Functional	Tested for the inhibition of prostromelysin activation with no preincubation period	Heteroaryl-fused 2-phenylisothiazolone inhibitors of cartilage breakdown. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT04880616	PHASE2	COMPLETED	Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor
NCT05021978	PHASE2	COMPLETED	A Clinical Trial of PRAX-944 in Participants With Essential Tremor
NCT05021991	PHASE2	COMPLETED	A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor
NCT05122650	PHASE2	COMPLETED	A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)
NCT05173012	PHASE2	COMPLETED	Study to Evaluate SAGE-324 in Participants With Essential Tremor
NCT05387642	PHASE2	WITHDRAWN	A Clinical Trial of PRAX-114 in Participants With Essential Tremor
NCT06312800	PHASE2	WITHDRAWN	Acamprosate and Methazolamide for Essential Tremor
NCT06821906	PHASE2	RECRUITING	Stereotactic Radiosurgery in the Treatment of Essential Tremor
NCT07074002	PHASE2	RECRUITING	Proof of Concept Study on BP1.4979 Effect on Essential Tremor
NCT07103265	PHASE2	NOT_YET_RECRUITING	Developing a New LIFU Neuromodulation Method to Suppress Tremor
NCT00001986	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT00016679	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT01304758	PHASE1	COMPLETED	ExAblate Transcranial MR Guided Focused Ultrasound in the Treatment of Essential Tremor