MMP16

gene
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Also known as MT3-MMPDKFZp761D112

Summary

MMP16 (matrix metallopeptidase 16, HGNC:7162) is a protein-coding gene on chromosome 8q21.3, encoding Matrix metalloproteinase-16 (P51512). Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin.

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. The encoded protein activates MMP2 by cleavage. This gene was once referred to as MT-MMP2, but was renamed as MT-MMP3 or MMP16.

Source: NCBI Gene 4325 — RefSeq curated summary.

At a glance

  • GWAS associations: 29
  • Clinical variants (ClinVar): 65 total
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_005941

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7162
Approved symbolMMP16
Namematrix metallopeptidase 16
Location8q21.3
Locus typegene with protein product
StatusApproved
AliasesMT3-MMP, DKFZp761D112
Ensembl geneENSG00000156103
Ensembl biotypeprotein_coding
OMIM602262
Entrez4325

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000286614, ENST00000520568, ENST00000522726, ENST00000544227

RefSeq mRNA: 1 — MANE Select: NM_005941 NM_005941

CCDS: CCDS6246

Canonical transcript exons

ENST00000286614 — 10 exons

ExonStartEnd
ENSE000010884028804666988046784
ENSE000010884088805612888056278
ENSE000012600178803201188041795
ENSE000013992038832707588327483
ENSE000034868058818647688186598
ENSE000034956028819715888197306
ENSE000035556998811870088118861
ENSE000036079758811650788116718
ENSE000036245528816766988167973
ENSE000036944728807460588074743

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 93.48.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2630 / max 65.6523, expressed in 881 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
938441.1805482
938430.9571463
938420.5846315
938410.3298173
938450.2110101

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
endothelial cellCL:000011593.48gold quality
tibiaUBERON:000097992.70gold quality
Brodmann (1909) area 23UBERON:001355490.61gold quality
cartilage tissueUBERON:000241890.34gold quality
postcentral gyrusUBERON:000258189.04gold quality
middle temporal gyrusUBERON:000277188.20gold quality
parietal lobeUBERON:000187288.13gold quality
entorhinal cortexUBERON:000272886.86gold quality
cortical plateUBERON:000534386.81gold quality
superior frontal gyrusUBERON:000266186.76gold quality
stromal cell of endometriumCL:000225586.19gold quality
ventricular zoneUBERON:000305382.55gold quality
primary visual cortexUBERON:000243682.17gold quality
occipital lobeUBERON:000202182.11gold quality
cerebellar vermisUBERON:000472081.98gold quality
ganglionic eminenceUBERON:000402381.46gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047381.41gold quality
mammary ductUBERON:000176580.75gold quality
corpus callosumUBERON:000233680.72gold quality
substantia nigra pars reticulataUBERON:000196679.22gold quality
medial globus pallidusUBERON:000247778.94gold quality
substantia nigra pars compactaUBERON:000196578.83gold quality
buccal mucosa cellCL:000233678.49gold quality
epithelium of mammary glandUBERON:000324478.24gold quality
skin of hipUBERON:000155477.67gold quality
globus pallidusUBERON:000187577.63gold quality
superior vestibular nucleusUBERON:000722777.19gold quality
temporal lobeUBERON:000187177.13gold quality
adrenal tissueUBERON:001830376.97gold quality
subthalamic nucleusUBERON:000190676.28gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-GEOD-100618yes2311.31
E-HCAD-35yes91.02
E-HCAD-25yes27.90
E-GEOD-84465yes25.55
E-ENAD-27yes8.15
E-ANND-3yes6.08
E-GEOD-93593yes5.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

290 targeting MMP16, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-126-5P100.0072.713180
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-340-5P100.0072.504437
HSA-MIR-9-5P100.0072.282361
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-450A-1-3P100.0069.331837
HSA-MIR-574-5P100.0066.01989
HSA-MIR-3646100.0073.565283
HSA-MIR-4776-3P100.0068.731340
HSA-MIR-3924100.0072.092394
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-366299.9973.825684
HSA-MIR-6759-5P99.9966.54785
HSA-MIR-453199.9969.703181
HSA-MIR-223-3P99.9970.141140
HSA-MIR-428299.9975.366408
HSA-MIR-511-3P99.9968.851467
HSA-MIR-453499.9966.581907
HSA-MIR-150-5P99.9966.691976
HSA-MIR-548P99.9872.253784
HSA-MIR-806899.9873.852376
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-569699.9872.364487
HSA-MIR-32-5P99.9875.211964
HSA-MIR-92A-3P99.9875.211960
HSA-MIR-92B-3P99.9875.251955
HSA-MIR-25-3P99.9874.601817

Literature-anchored findings (GeneRIF, showing 35)

  • down-regulation of most MT-MMPs is typical for prostate carcinoma; seems to occur mainly in epithelial cells (PMID:12661033)
  • Results report the structure of the catalytic domain (cd) of the membrane-type matrix metalloproteinase MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. (PMID:14741217)
  • MT3-MMP is not only important in matrix degradation but also may affect the function of focal adhesions through FAK cleavage. (PMID:15044209)
  • Type-3 metalloproteinases, are identified as the triggering agents that independently confer cancer cells with the ability to proteolytically efface the BM scaffolding, initiate the assembly of invasive pseudopodia, and propagate transmigration. (PMID:16983145)
  • Chondroitin-4-sulfate, which is expressed on tumour cell surface, can function to bind to pro-MMP-2 and facilitate its activation by MT3-MMP-expressing tumour cells to enhance invasion and metastasis (PMID:17217338)
  • We have demonstrated the expression of MT3-MMP in hepatocellular carcinoma tissues (HCC) and that the expression in HCC significantly correlates with capsular invasion. (PMID:17419254)
  • MMP16 polymorphisms appear to influence not only the pulmonary expression and function of MMP16 but also the risk of bronchopulmonary dysplasia (PMID:18784838)
  • miR-146b is involved in glioma cell migration and invasion by targeting MMP16; implicating miR-146b as a metastasis-inhibiting miRNA in glioma (PMID:19265686)
  • Matrix metalloproteinase 16 (MMP16) was a downstream target of miR-146b-5p. (PMID:21823013)
  • MT3-MMP is a matrix-dependent modifier of the invasive tumor cell functions during melanoma progression (PMID:22164270)
  • Data show that MMP16 is regulated by miR-146a in spontaneously differentiated Caco-2 cells. (PMID:22348245)
  • The overexpression of miR-146b-5p in glioblastoma cell lines led to MMP16 mRNA silencing, MMP2 inactivation, and the inhibition of tumour cell migration and invasion. (PMID:23796692)
  • E2F1 acts as a transcriptional activator for MMPs and directly enhances MMP transcription by binding to E2F1 binding sequences in the promoter, or indirectly activates MMPs (MMP-9 and MMP-16)through enhanced Sp1 and NF-kappa B (PMID:24755270)
  • the results support a role for MMP16 in promoting invasive properties of the meningioma tumours (PMID:24989599)
  • Expression of MMP-16 in HTB9 and T24 cells increases following transforming growth factorbeta1 treatment. (PMID:25017509)
  • MMP16 is a putative indicator of adverse melanoma prognosis. (PMID:25808867)
  • These results demonstrate that the MT3-MMP promoter is frequently hypermethylated in colorectal cancer and that downregulation of MT3-MMP may be important for cell migration in colorectal cancer. (PMID:26002729)
  • results suggest that miR-145 functions as a tumor metastasis suppressor gene by down-regulating MMP16 and may be a potential target in osteosarcoma treatment (PMID:26605780)
  • more severe intervertebral disc degeneration is correlated with higher matrix metallopeptidase 16 (PMID:27227700)
  • the present findings indicate that MT3-MMP is down-regulated in ESCC, which correlates to lymph node metastasis and poor survival of patients with this disease. (PMID:27292876)
  • MMP16 was highly expressed and correlated with poor prognosis in gastric cancer patients by promoting proliferation and invasion of gastric cancer cells (PMID:27340864)
  • Findings suggest that these MMP16 rs10090371, ADAMTS3 rs788935, TLL2 rs10882807 and MMP9 rs3918251 may be promising prognostic biomarkers for cutaneous melanoma specific survival (CMSS). (PMID:28796414)
  • Overexpression of MMP2 and MMP16 in endometrial cancerous tissues corresponded to down-regulation of miR-377, miR-382 and miR-410, while decreased expression of TIMP2 was associated with miR-200b up-regulation. (PMID:28871006)
  • HOXA11-AS could promote renal cancer cells growth and invasion by modulating miR-146b-5p-MMP16 axis. (PMID:29953617)
  • A protective polymorphism in MMP16, improved blood gas levels, and chronic obstructive pulmonary diseases: Family and two population-based studies. (PMID:32196811)
  • LINC01121 induced intervertebral disc degeneration via modulating miR-150-5p/MMP16 axis. (PMID:32436632)
  • Role of lncRNA NEAT1 mediated by YY1 in the development of diabetic cataract via targeting the microRNA-205-3p/MMP16 axis. (PMID:32572898)
  • Knockdown of MMP16 inhibits cell proliferation and invasion in chordoma in vitro. (PMID:33210500)
  • Association between MMP16 rs60298754 and clinical phenotypes of Parkinson’s disease in southern Chinese. (PMID:33241532)
  • microRNA-4429-5p suppresses the malignant development of colon cancer by targeting matrix metalloproteinase 16. (PMID:34448115)
  • LncRNA NEAT1 regulates MMP-16 by targeting miR-200a/b to aggravate inflammation in asthma. (PMID:34448644)
  • Circular RNA hsa_circ_0002360 promotes non-small cell lung cancer progression through upregulating matrix metalloproteinase 16 and sponging multiple micorRNAs. (PMID:34747300)
  • Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC). (PMID:35062057)
  • MMP16 as NSCL +/- P Susceptible Gene in Western Han Chinese. (PMID:36120833)
  • M1 macrophage-derived exosomes containing miR-150 inhibit glioma progression by targeting MMP16. (PMID:37244635)

Cross-species orthologs

9 orthologs

OrganismSymbolGene ID
danio_reriommp16bENSDARG00000058876
danio_rerioENSDARG00000116438
mus_musculusMmp16ENSMUSG00000028226
rattus_norvegicusMmp16ENSRNOG00000005708
caenorhabditis_elegansWBGENE00010524
caenorhabditis_elegansWBGENE00012185
caenorhabditis_elegansWBGENE00012364
caenorhabditis_elegansWBGENE00016283
caenorhabditis_elegansWBGENE00194737

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), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-16P51512 (reviewed: P51512)

Alternative names: MMP-X2, Membrane-type matrix metalloproteinase 3, Membrane-type-3 matrix metalloproteinase

All UniProt accessions (2): P51512, E5RJA7

UniProt curated annotations — full annotation on UniProt →

Function. Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin. Activates progelatinase A. Involved in the matrix remodeling of blood vessels. Isoform short cleaves fibronectin and also collagen type III, but at lower rate. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells.

Subunit / interactions. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan.

Subcellular location. Cell membrane Secreted. Extracellular space. Extracellular matrix. Cell surface.

Tissue specificity. Expressed in heart, brain, placenta, ovary and small intestine. Isoform Short is found in the ovary.

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

Activity regulation. TIMP-2 shows little inhibitory activity compared to TIMP-1. TIMP-1 seems to have less binding affinity than TIMP-2 for the short isoform.

Cofactor. Binds 2 zinc 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.

Isoforms (2)

UniProt IDNamesCanonical?
P51512-1Longyes
P51512-2Short, SM3

RefSeq proteins (1): NP_005932* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000585Hemopexin-like_domDomain
IPR001818Pept_M10_metallopeptidaseDomain
IPR002477Peptidoglycan-bd-likeDomain
IPR006026Peptidase_MetalloDomain
IPR018486Hemopexin_CSConserved_site
IPR018487Hemopexin-like_repeatRepeat
IPR021158Pept_M10A_Zn_BSBinding_site
IPR021190Pept_M10AFamily
IPR021805Pept_M10A_metallopeptidase_CDomain
IPR024079MetalloPept_cat_dom_sfHomologous_superfamily
IPR033739M10A_MMPDomain
IPR036365PGBD-like_sfHomologous_superfamily
IPR036375Hemopexin-like_dom_sfHomologous_superfamily

Pfam: PF00045, PF00413, PF01471, PF11857

UniProt features (53 total): binding site 18, strand 11, repeat 4, helix 3, topological domain 2, splice variant 2, turn 2, signal peptide 1, propeptide 1, region of interest 1, short sequence motif 1, compositionally biased region 1, active site 1, chain 1, glycosylation site 1, disulfide bond 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
1RM8X-RAY DIFFRACTION1.8

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P51512-F177.060.38

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): 247

Ligand- & substrate-binding residues (18): 101 (in inhibited form); 183; 193; 195; 200; 201; 203; 205; 208; 215; 217; 219

Disulfide bonds (1): 343–532

Glycosylation sites (1): 83

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

IDPathway
R-HSA-1592389Activation of Matrix Metalloproteinases
R-HSA-9839383TGFBR3 PTM regulation
R-HSA-1474228Degradation of the extracellular matrix
R-HSA-1474244Extracellular matrix organization
R-HSA-162582Signal Transduction
R-HSA-9006936Signaling by TGFB family members
R-HSA-9839373Signaling by TGFBR3

MSigDB gene sets: 251 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, AAGCAAT_MIR137, TAATAAT_MIR126, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, AREB6_03, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOZGIT_ESR1_TARGETS_DN, GOCC_CELL_SURFACE, CERVERA_SDHB_TARGETS_1_DN, LIEN_BREAST_CARCINOMA_METAPLASTIC, GOBP_REPLACEMENT_OSSIFICATION, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (11): skeletal system development (GO:0001501), endochondral ossification (GO:0001958), proteolysis (GO:0006508), protein processing (GO:0016485), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), chondrocyte proliferation (GO:0035988), embryonic cranial skeleton morphogenesis (GO:0048701), craniofacial suture morphogenesis (GO:0097094), ossification (GO:0001503), bone development (GO:0060348)

GO Molecular Function (8): metalloendopeptidase activity (GO:0004222), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular matrix (GO:0031012), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

CategoryPathways
Degradation of the extracellular matrix1
Signaling by TGFBR31
Extracellular matrix organization1
Signal Transduction1
Signaling by TGFB family members1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
cranial skeletal system development2
catalytic activity2
system development1
replacement ossification1
endochondral bone morphogenesis1
protein metabolic process1
proteolysis1
protein maturation1
extracellular structure organization1
external encapsulating structure organization1
catabolic process1
collagen metabolic process1
cell population proliferation1
embryonic skeletal system morphogenesis1
anatomical structure morphogenesis1
bone morphogenesis1
multicellular organismal process1
skeletal system development1
animal organ development1
endopeptidase activity1
metallopeptidase activity1
enzyme regulator activity1
molecular function activator activity1
transition metal ion binding1
aminopeptidase activity1
metalloexopeptidase activity1
hydrolase activity1
catalytic activity, acting on a protein1
peptidase activity1
cation binding1
Golgi apparatus1
intracellular organelle lumen1
membrane1
cell periphery1
external encapsulating structure1

Protein interactions and networks

STRING

1124 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MMP16SPOCK3Q9BQ16843
MMP16SPOCK2Q92563817
MMP16SPOCK1Q08629797
MMP16TIMP2P16035768
MMP16TIMP1P01033740
MMP16TIMP3P35625611
MMP16TIMP4Q99727593
MMP16CD44P16070555
MMP16PLGP00747553
MMP16COL15A1P39059521
MMP16NT5C2P49902507
MMP16COL12A1Q99715504
MMP16PLATP00750495
MMP16CSPG4Q6UVK1490
MMP16VRK2Q86Y07477

IntAct

2 interactions, top by confidence:

ABTypeScore
MMP16Gorasp2psi-mi:“MI:0915”(physical association)0.370

BioGRID (15): MMP16 (Affinity Capture-RNA), MMP16 (Affinity Capture-MS), MMP17 (Negative Genetic), MMP24 (Negative Genetic), MMP16 (Negative Genetic), MMP16 (Negative Genetic), MMP16 (Negative Genetic), MMP16 (Negative Genetic), MMP16 (Negative Genetic), MMP16 (Negative Genetic), MMP20 (Negative Genetic), MMP27 (Negative Genetic), MMP7 (Negative Genetic), MMP8 (Negative Genetic), MMP16 (Affinity Capture-RNA)

ESM2 similar proteins: A0A044RE18, B4F6N6, B5DF27, E1C3U7, F1QQC3, G5ECN9, O17798, O35548, O64481, P09231, P09958, P13134, P16519, P21661, P23188, P23377, P28840, P28841, P29119, P29120, P29122, P29145, P29146, P30432, P41413, P51512, P51559, P58022, P63239, P63240, P91863, Q03333, Q04592, Q08B63, Q09175, Q28193, Q5REC2, Q63415, Q8QGP3, Q8SQJ3

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.

AEffectBMechanism
MMP16up-regulatesECM_disassembly
MMP16down-regulatesECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance49
Likely benign1
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3662 predictions. Top by Δscore:

VariantEffectΔscore
8:88035975:A:Cacceptor_gain1.0000
8:88046663:GCATA:Gdonor_loss1.0000
8:88046664:CATAC:Cdonor_loss1.0000
8:88046665:ATAC:Adonor_loss1.0000
8:88046666:TACCA:Tdonor_loss1.0000
8:88046667:ACCAT:Adonor_loss1.0000
8:88046692:C:CAdonor_gain1.0000
8:88046782:TAT:Tacceptor_gain1.0000
8:88056123:CTGA:Cdonor_loss1.0000
8:88056124:TGA:Tdonor_loss1.0000
8:88056125:GA:Gdonor_loss1.0000
8:88056126:A:AGdonor_loss1.0000
8:88056127:C:Tdonor_loss1.0000
8:88056127:CCTGT:Cdonor_gain1.0000
8:88056277:ACC:Aacceptor_loss1.0000
8:88056283:A:Cacceptor_gain1.0000
8:88118697:TA:Tdonor_loss1.0000
8:88118698:A:ACdonor_gain1.0000
8:88118699:C:CAdonor_loss1.0000
8:88118699:C:CCdonor_gain1.0000
8:88141048:A:Cdonor_gain1.0000
8:88141086:T:Adonor_gain1.0000
8:88167663:ACTT:Adonor_loss1.0000
8:88167666:TACC:Tdonor_loss1.0000
8:88167667:A:ACdonor_gain1.0000
8:88167667:AC:Adonor_gain1.0000
8:88167667:ACCAT:Adonor_gain1.0000
8:88167668:C:CGdonor_gain1.0000
8:88167668:CC:Cdonor_gain1.0000
8:88167668:CCA:Cdonor_gain1.0000

AlphaMissense

4024 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
8:88046718:C:AW480C1.000
8:88046718:C:GW480C1.000
8:88046720:A:GW480R1.000
8:88046720:A:TW480R1.000
8:88074674:A:GW385R1.000
8:88074674:A:TW385R1.000
8:88074727:C:GR367P1.000
8:88074731:A:GW366R1.000
8:88074731:A:TW366R1.000
8:88116514:A:TV359D1.000
8:88116562:C:GC343S1.000
8:88116563:A:TC343S1.000
8:88118726:T:CD282G1.000
8:88118727:C:GD282H1.000
8:88118738:A:TL278Q1.000
8:88118779:C:AM264I1.000
8:88118779:C:GM264I1.000
8:88118779:C:TM264I1.000
8:88118780:A:CM264R1.000
8:88118780:A:GM264T1.000
8:88118786:G:TA262D1.000
8:88118787:C:GA262P1.000
8:88118801:G:AS257F1.000
8:88118802:A:GS257P1.000
8:88118803:A:CH256Q1.000
8:88118803:A:TH256Q1.000
8:88118804:T:CH256R1.000
8:88118805:G:CH256D1.000
8:88118810:A:GL254S1.000
8:88118813:C:TG253E1.000

dbSNP variants (sampled 300 via entrez): RS1000000891 (8:88181277 T>C), RS1000007563 (8:88049436 T>C), RS1000018420 (8:88051498 T>A,C), RS1000023598 (8:88185518 A>G), RS1000039588 (8:88309064 T>C), RS1000039823 (8:88265720 G>T), RS1000042357 (8:88249992 A>G,T), RS1000048837 (8:88244356 C>T), RS1000051779 (8:88268776 A>C), RS1000056161 (8:88185066 T>A), RS1000065474 (8:88271622 T>A), RS1000080170 (8:88100563 G>A), RS1000083333 (8:88166315 G>C), RS1000089671 (8:88296197 G>A), RS1000097337 (8:88224024 T>C)

Disease associations

OMIM: gene MIM:602262 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

StudyTraitp-value
GCST001242_12Schizophrenia2.000000e-07
GCST001440_1Body mass index and cholesterol (psychopharmacological treatment)6.000000e-08
GCST001565_11Schizophrenia6.000000e-08
GCST001877_37Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)3.000000e-08
GCST002078_1Migraine without aura1.000000e-08
GCST002149_21Schizophrenia3.000000e-08
GCST002539_74Schizophrenia1.000000e-08
GCST003073_5Cerebral amyloid deposition (PET imaging)7.000000e-07
GCST004049_30Cough in response to angiotensin-converting enzyme inhibitor drugs3.000000e-06
GCST004521_109Autism spectrum disorder or schizophrenia2.000000e-08
GCST004521_288Autism spectrum disorder or schizophrenia5.000000e-08
GCST004946_102Schizophrenia1.000000e-08
GCST006803_80Schizophrenia7.000000e-09
GCST006941_30Irritable mood6.000000e-09
GCST006979_467Heel bone mineral density1.000000e-16
GCST007201_100Schizophrenia3.000000e-08
GCST007201_311Schizophrenia7.000000e-07
GCST008018_5Sweet taste perception in obesity with metabolic syndrome8.000000e-06
GCST008103_110Bipolar disorder4.000000e-06
GCST010002_308Refractive error1.000000e-10
GCST90000025_367Appendicular lean mass4.000000e-26
GCST90020024_179A body shape index1.000000e-08
GCST90020024_181A body shape index7.000000e-12
GCST90020025_1022Waist-to-hip ratio adjusted for BMI2.000000e-08
GCST90020025_1023Waist-to-hip ratio adjusted for BMI1.000000e-11
GCST90020027_1379Waist-hip index6.000000e-09
GCST90020027_1380Waist-hip index6.000000e-12
GCST90020029_87Waist circumference adjusted for body mass index2.000000e-08
GCST90020029_89Waist circumference adjusted for body mass index2.000000e-11

EFO canonical traits (8, from GWAS)

EFO IDTrait name
EFO:0004340body mass index
EFO:0007707cerebral amyloid deposition measurement
EFO:0005325response to angiotensin-converting enzyme inhibitor
EFO:0009594irritability measurement
EFO:0009270heel bone mineral density
EFO:0004980appendicular lean mass
EFO:0007789BMI-adjusted waist circumference
EFO:0007788BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2200 (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).

MoleculeNamePhasePatents
CHEMBL279785MARIMASTAT329,447
CHEMBL19611ILOMASTAT212,065

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 (2 total), top 2:

LigandActionAffinityParameter
ilomastatInhibition8.1pIC50
SL422Inhibition7.46pKi

ChEMBL bioactivities

52 potent at pChembl≥5 of 57 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.51IC500.31nMCHEMBL471537
9.00IC501nMCHEMBL234530
8.81IC501.56nMCHEMBL515980
8.17IC506.8nMCGS-27023A
8.10IC508nMILOMASTAT
7.94IC5011.4nMCHEMBL472899
7.80IC5016nMCHEMBL148214
7.68IC5021nMCHEMBL147882
7.66IC5022nMCHEMBL358539
7.50IC5032nMCHEMBL573715
7.46Ki35nMCHEMBL88520
7.46IC5035nMCHEMBL147881
7.41IC5039nMCHEMBL1939846
7.40IC5040nMCHEMBL148171
7.36IC5044nMCHEMBL234529
7.29IC5051nMCHEMBL561963
7.29IC5051nMCHEMBL179288
7.25IC5056nMCHEMBL146718
6.97Ki107nMCHEMBL91636
6.89IC50130nMCHEMBL573714
6.89IC50130nMCHEMBL584365
6.82IC50150nMCHEMBL572780
6.75IC50177nMCHEMBL147489
6.74IC50184nMCHEMBL146289
6.73IC50186nMCHEMBL234735
6.70IC50202nMCHEMBL148406
6.66IC50220nMCHEMBL574370
6.33IC50470nMCHEMBL574605
6.14IC50730nMCHEMBL573936
6.05IC50900nMCHEMBL181244
6.03IC50940nMBAY-7598
6.00IC50996nMCHEMBL515083
5.96IC501100nMCHEMBL584147
5.96IC501100nMCHEMBL1939844
5.92IC501200nMCHEMBL573934
5.89IC501300nMCHEMBL575896
5.80Ki1599nMCHEMBL148169
5.78IC501677nMCHEMBL356124
5.74IC501839nMCHEMBL424130
5.70Ki2000nMCHEMBL325163
5.66IC502200nMCHEMBL1939845
5.37IC504300nMCHEMBL573935
5.33IC504633nMCHEMBL147604
5.30IC505000nMCHEMBL550548
5.29IC505100nMCHEMBL574589
5.22IC506000nMCHEMBL584122
5.20IC506300nMCHEMBL579068
5.19IC506500nMCHEMBL579067
5.00IC501e+04nMMARIMASTAT

PubChem BioAssay actives

51 with measured affinity, of 82 total; 48 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(2R)-N-hydroxy-3-methyl-2-[[2-oxo-2-[2-(4-sulfamoylphenyl)ethylamino]ethyl]-(4-phenoxyphenyl)sulfonylamino]butanamide413962: Inhibition of MMP16ic500.0003uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-phenoxyphenyl)sulfonylamino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide413962: Inhibition of MMP16ic500.0010uM
2-[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-phenoxyphenyl)sulfonylamino]acetic acid413962: Inhibition of MMP16ic500.0016uM
(2R)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(pyridin-3-ylmethyl)amino]-3-methylbutanamide;hydrochloride413962: Inhibition of MMP16ic500.0068uM
(2R)-N’-hydroxy-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0080uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-phenoxyphenyl)sulfonylamino]acetic acid413962: Inhibition of MMP16ic500.0114uM
N,6-dihydroxy-7-methoxy-2-(4-methoxyphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0160uM
N,6-dihydroxy-2-(4-methylphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0210uM
N-hydroxy-2-(4-methoxyphenyl)sulfonyl-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0220uM
N-hydroxy-2-[2-[4-(4-methoxyphenoxy)phenyl]sulfonylphenyl]acetamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.0320uM
(6S,7R,10S)-6-N-hydroxy-10-N-[2-(methylamino)-2-oxoethyl]-7-(2-methylpropyl)-8-oxo-2-oxa-9-azabicyclo[10.2.2]hexadeca-1(14),12,15-triene-6,10-dicarboxamide109573: Inhibition of matrix metalloprotease-16ki0.0350uM
2-(benzenesulfonyl)-N-hydroxy-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0350uM
(3R)-1-hydroxy-4-(4-phenoxyphenyl)sulfonyl-3-propan-2-ylpiperazine-2,6-dione641681: Inhibition of human recombinant MMP16 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 4 hrs measured every 15 secs for 20 mins by fluorescence analysisic500.0390uM
2-(benzenesulfonyl)-N,6-dihydroxy-7-methoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0400uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide413962: Inhibition of MMP16ic500.0440uM
(2R)-N-hydroxy-3-methyl-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]butanamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.0510uM
N-hydroxy-3-methyl-2-[propan-2-yloxy-[4-(4-propan-2-ylphenyl)phenyl]sulfonylamino]butanamide419744: Inhibition of human recombinant MMP16ic500.0510uM
N-hydroxy-2-(4-methylphenyl)sulfonyl-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.0560uM
(8S,11R,12S)-12-N-hydroxy-11-(2-methylpropyl)-8-N-(2-morpholin-4-yl-2-oxoethyl)-2,10-dioxo-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxamide109573: Inhibition of matrix metalloprotease-16ki0.1070uM
N-hydroxy-2-[2-(4-methoxyphenyl)sulfonylphenyl]acetamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.1300uM
N-hydroxy-2-[2-[4-(4-methoxyphenyl)phenyl]sulfonylphenyl]acetamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.1300uM
N-hydroxy-2-[2-[4-(4-methoxyphenyl)phenyl]sulfonylphenyl]propanamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.1500uM
N,6-dihydroxy-2-(4-nitrophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.1770uM
2-(benzenesulfonyl)-N,6-dihydroxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.1840uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-phenylphenyl)sulfonylamino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide413962: Inhibition of MMP16ic500.1860uM
2-(4-aminophenyl)sulfonyl-N,6-dihydroxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic500.2020uM
N-hydroxy-2-[2-(4-phenylphenyl)sulfonylphenyl]acetamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.2200uM
N-hydroxy-2-[2-(4-phenylphenyl)sulfonylphenyl]propanamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.4700uM
2-[2-[4-(4-methoxyphenyl)phenyl]sulfonylphenyl]acetic acid440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic500.7300uM
N-hydroxy-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]acetamide419744: Inhibition of human recombinant MMP16ic500.9000uM
2-[[2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]acetic acid413962: Inhibition of MMP16ic500.9960uM
2-[2-[4-(4-methoxyphenyl)phenyl]sulfonylphenyl]propanoic acid440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic501.1000uM
(3R)-1-hydroxy-4-(4-methoxyphenyl)sulfonyl-3-propan-2-ylpiperazine-2,6-dione641681: Inhibition of human recombinant MMP16 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 4 hrs measured every 15 secs for 20 mins by fluorescence analysisic501.1000uM
N-hydroxy-2-[4-(4-methoxyphenyl)phenyl]sulfonylbenzamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic501.2000uM
N-hydroxy-2-(4-phenoxyphenyl)sulfonylbenzamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic501.3000uM
(2R)-N-hydroxy-2-[(3S)-3-methyl-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]-2-oxopyrrolidin-1-yl]propanamide109572: Affinity for Matrix metalloprotease-16 (MMP-16)ki1.5990uM
N,6-dihydroxy-2-(4-methoxyphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic501.6770uM
2-(2,5-dichlorophenyl)sulfonyl-N,6-dihydroxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic501.8390uM
(8S,11R,12S)-12-N-hydroxy-8-N-(2-morpholin-4-yl-2-oxoethyl)-2,10-dioxo-11-[[4-[2-(trifluoromethyl)phenyl]phenyl]methyl]-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxamide109574: Inhibition of matrix metalloprotease-16ki2.0000uM
(3R)-1-hydroxy-4-(4-phenylphenyl)sulfonyl-3-propan-2-ylpiperazine-2,6-dione641681: Inhibition of human recombinant MMP16 using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated for 4 hrs measured every 15 secs for 20 mins by fluorescence analysisic502.2000uM
2-[2-(4-phenylphenyl)sulfonylphenyl]acetic acid440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic504.3000uM
2-(2,5-dichlorophenyl)sulfonyl-N-hydroxy-6-phenylmethoxy-3,4-dihydro-1H-isoquinoline-1-carboxamide109575: Inhibition of matrix metalloprotease-16 (MMP-16)ic504.6330uM
(2R)-2-[[4-[4-[(4-chlorophenyl)methoxy]phenyl]phenyl]sulfonyl-propan-2-yloxyamino]-N-hydroxy-3-methylbutanamide419744: Inhibition of human recombinant MMP16ic505.0000uM
N-hydroxy-2-(4-phenylphenyl)sulfonylbenzamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic505.1000uM
N-hydroxy-2-[4-(4-methoxyphenoxy)phenyl]sulfonylbenzamide440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic506.0000uM
2-[2-(4-phenylphenyl)sulfonylphenyl]propanoic acid440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic506.3000uM
2-[2-[4-(4-methoxyphenoxy)phenyl]sulfonylphenyl]acetic acid440428: Inhibition of human recombinant pro-MMP16 catalytic domain after 4 hrs by fluorimetryic506.5000uM
(2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide1274673: Inhibition of MMP16 (unknown origin) catalytic domain 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 assayic5010.0000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
trichostatin Aaffects cotreatment, increases expression3
entinostatdecreases expression, affects cotreatment2
Resveratroldecreases expression, affects cotreatment2
Vorinostatdecreases expression, increases expression2
Arsenicaffects methylation, affects cotreatment, decreases expression, increases abundance2
Estradioldecreases expression, affects cotreatment2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
Valproic Aciddecreases expression2
aristolochic acid Idecreases expression1
geldanamycinincreases expression1
methylmercuric chloridedecreases expression1
bisphenol Adecreases methylation1
afimoxifenedecreases expression, decreases reaction1
sodium arseniteaffects cotreatment, decreases expression, increases abundance1
cobaltous chloridedecreases expression1
manganese chlorideaffects cotreatment, decreases expression, increases abundance1
potassium chromate(VI)decreases expression1
nickel sulfatedecreases expression1
mercuric bromidedecreases expression1
glycidamidedecreases expression1
chromium hexavalent iondecreases expression1
CGS 27023Aaffects activity1
2-palmitoylglycerolincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression, increases expression1
dorsomorphinaffects cotreatment, decreases expression, increases expression1
Arsenic Trioxidedecreases expression1
Acetaminophenincreases expression1
Benzo(a)pyreneincreases methylation1
Calcitrioldecreases expression, affects cotreatment1
Cisplatinincreases expression1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1005428BindingInhibition of MMP16 up to 100 uMSpecific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

CellosaurusNameCategorySex
CVCL_SY62HAP1 MMP16 (-) 1Cancer cell lineMale
CVCL_SY63HAP1 MMP16 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.