MMP20

Summary

MMP20 (matrix metallopeptidase 20, HGNC:7167) is a protein-coding gene on chromosome 11q22.2, encoding Matrix metalloproteinase-20 (O60882). Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP).

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 protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3.

Source: NCBI Gene 9313 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelogenesis imperfecta hypomaturation type 2A2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 208 total — 7 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7167
Approved symbol	MMP20
Name	matrix metallopeptidase 20
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137674
Ensembl biotype	protein_coding
OMIM	604629
Entrez	9313

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000260228, ENST00000542305, ENST00000544938

RefSeq mRNA: 1 — MANE Select: NM_004771 NM_004771

CCDS: CCDS8318

Canonical transcript exons

ENST00000260228 — 10 exons

Exon	Start	End
ENSE00000930301	102576832	102577426
ENSE00000930303	102593439	102593595
ENSE00000930304	102594621	102594757
ENSE00000930306	102608937	102609098
ENSE00000930307	102609905	102610030
ENSE00000930308	102611755	102611903
ENSE00000930309	102616812	102617059
ENSE00000930310	102625194	102625332
ENSE00003595560	102606535	102606676
ENSE00003668372	102579039	102579142

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 68.18.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	68.18	gold quality
testis	UBERON:0000473	66.21	gold quality
right testis	UBERON:0004534	66.20	gold quality
sperm	CL:0000019	64.11	silver quality
male germ cell	CL:0000015	63.12	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.04	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	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
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
quadriceps femoris	UBERON:0001377	48.67	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
oviduct epithelium	UBERON:0004804	48.00	gold quality
sural nerve	UBERON:0015488	47.98	silver quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
epithelial cell of pancreas	CL:0000083	47.68	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
deltoid	UBERON:0001476	47.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting MMP20, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-10393-5P	99.65	68.01	1368

Literature-anchored findings (GeneRIF, showing 32)

• Enamelysin and collagen XVIII were co-localized in the developing enamel matrix and stratum intermedium and in the enamel-like tumor matrix of odontogenic tumors. (PMID:15296943)
• A mutation in the MMP-20 gene has been identified and associated with amelogenesis imperfecta. (PMID:15744043)
• c-Jun is a key regulatory element for MMP-20 expression (PMID:17611094)
• Binding of the P41T mutant amelogenin for matrix metalloproteinase 20 was significantly lower than that of wild-type amelogenin. (PMID:18434575)
• A total of 463 individuals from 54 families were evaluated and mutations in the AMEL, ENAM and KLK4 genes were identified. (PMID:18714142)
• were able to find SNPs in the matrix metallopeptidase gene MMP20(GeneID 9313) that are significantly associated with kidney aging. (PMID:19834535)
• In a family with a hypomaturation-type enamel defect, mutational and haplotype analyses revealed an amelogenesis imperfecta-causing point mutation in exon 6 of MMP20 that results in a single amino acid substitution in the hemopexin domain. (PMID:19966041)
• Associations between tooth agenesis and MMP1 (p=0.007), and MMP20 (p=0.03) were found in Brazilian families. MMP20 continued to be associated with tooth agenesis (p=0.01). Mmp20 was not expressed during the initial stages of tooth development. (PMID:21144496)
• MMP-20 is overexpresssed in LSCC compared with the adjacent normal laryngeal epithelium. (PMID:21466263)
• hypocalcified amelogenesis imperfecta, Witkop type III, was unrelated to previously described mutations in the ENAM or MMP-20 genes (PMID:21504268)
• Variation in MMP20 may be associated with caries experience mainly in Caucasian subjects with poor oral health habits. (PMID:22330321)
• The results identify MMP-20 as a broad activator of pro-KLKs, suggesting the potential for intersection of the KLK and MMP axes under pathological dysregulation of MMP-20 expression. (PMID:23241590)
• amelogenesis imperfecta-causing mutations were identified in three of the probands: 2)a novel missense transition mutation in both MMP20 alleles (g.15390A>G; c.611A>G; p.His204Arg) that substituted arginine for histidine. (PMID:23355523)
• mineralized content slightly decreased; magnesium substituting for calcium in crystal. anomalies affected enamel with minimal interrod enamel; apatite crystals perpendicular to enamel prisms, suggesting possible new role for MMP20 in enamel formation. (PMID:23625376)
• Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation. (PMID:23953525)
• expression of MMP-20 and co-expression and potential interaction with DSPP in human major salivary gland tissues (PMID:25805840)
• Novel homozygous mutation MMP20 (c.1054G>A, p.Glu352Lys) genes were identified in amelogenesis imperfect consanguinity. Mutant MMP20 was expressed at a normal level but secreted only minimally with proteolytic function. (PMID:26124219)
• The growth of choroidal neovascularization in AMD would be affected by 2 genes: MMP20, a newly confirmed gene expressed in the retina, and ARMS2/HTRA1, a well-known susceptibility gene for AMD. (PMID:26337002)
• The expression of MMP20 was lower in calcifying cystic odontogenic tumor when compared to all tumors and cysts. (PMID:26558991)
• Levels of matrix metalloproteinases MMP-19 and MMP-20 expression are significantly increased in pancreatic ductal adenocarcinoma (PDAC). (PMID:26692439)
• DSPP-MMP20 pair may play a role in the normal turnover of cell surface proteins and/or repair of pericellular matrix proteins of the basement membranes in the metabolically active duct epithelial system of the nephrons. (PMID:27666430)
• The article data showed that MMP20 rs1784418 C>T (Matrix metalloproteinase 20) appears to protect against dental caries, but its effects are likely to be more marked in certain populations. (PMID:27992873)
• common variants at 11q22.2 within MMP20 associate with neuroblastoma cases harboring 11q deletion (rs10895322) (PMID:28924153)
• The levels of MMP20 silencing-induced downregulation differed amongst CSC markers, with ABCG2 and CD44 showing more pronounced downregulations. (PMID:30002682)
• The polymorphisms in MMP2, MMP9 and MMP20 genes were not statistically associated with human dental fluorosis. (PMID:30639979)
• Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts. Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers. DSPP expression increased significantly with tumor stage in all cancers examined. (PMID:30932369)
• the minimum alleles of rs10895322, rs1784424, rs3781788, and rs1573954 correlated with an increased risk of alcohol-induced ONFH (P<0.05). Genetic model analysis revealed significant associations of 9 SNPs with alcohol-induced ONFH occurrence after adjustment for age (P<0.05): 2 protective SNPs (rs1711423 and rs1784418) and 7 high-risk SNPs (rs10895322, rs1784424, rs3781788, rs7126560, rs1573954, rs1711399, rs2292730). (PMID:31106781)
• AMELX and ODAM variations was not different between two populations of schoolchildren with respect to dental fluorosis (DF) severity; however, the presence of rs1784418 differed between phenotypes with regard to susceptibility to DF. Therefore, MMP20 might be related to the various phenotypes of DF (PMID:31838295)
• Dental malformations associated with biallelic MMP20 mutations. (PMID:32495503)
• The possible influence of genetic aetiological factors on molar-incisor hypomineralisation. (PMID:32777581)
• Lung development, repair and cancer: A study on the role of MMP20 gene in adenocarcinoma. (PMID:33914777)
• Association between LTF/MMP20/CA6/TAS1R2 polymorphisms and susceptibility to dental caries. (PMID:39212776)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp25b	ENSDARG00000010556
danio_rerio	hpxa	ENSDARG00000012609
danio_rerio	mmp25a	ENSDARG00000077290
mus_musculus	Mmp20	ENSMUSG00000018620
rattus_norvegicus	Mmp20	ENSRNOG00000021896
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), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-20 — O60882 (reviewed: O60882)

Alternative names: Enamel metalloproteinase, Enamelysin

All UniProt accessions (1): O60882

UniProt curated annotations — full annotation on UniProt →

Function. Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP). May play a central role in tooth enamel formation. Cleaves aggrecan at the ‘360-Asn-|-Phe-361’ site.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed specifically in the enamel organ.

Post-translational modifications. Autoactivates at least at the 107-Asn-|-Tyr-108 site.

Disease relevance. Amelogenesis imperfecta, hypomaturation type, 2A2 (AI2A2) [MIM:612529] A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 Zn(2+) ions per subunit. Binds 2 calcium 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_004762* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001818	Pept_M10_metallopeptidase	Domain
IPR002477	Peptidoglycan-bd-like	Domain
IPR006026	Peptidase_Metallo	Domain
IPR018487	Hemopexin-like_repeat	Repeat
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.B6 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (52 total): binding site 21, strand 11, sequence variant 5, repeat 4, helix 3, signal peptide 1, propeptide 1, chain 1, disulfide bond 1, sequence conflict 1, turn 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JSD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60882-F1	83.91	0.61

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): 227

Ligand- & substrate-binding residues (21): 164; 165; 166; 176; 178; 183; 184; 186; 188; 191; 197; 198 …

Disulfide bonds (1): 296–483

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-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation

MSigDB gene sets: 118 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, chr11q22, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TOOTH_MINERALIZATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_ENAMEL_MINERALIZATION, MODULE_99, TGANTCA_AP1_C, GOBP_AMELOGENESIS, TATA_C, GOBP_EXTRACELLULAR_MATRIX_DISASSEMBLY, GOBP_ODONTOGENESIS_OF_DENTIN_CONTAINING_TOOTH, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_ODONTOGENESIS, TAATTA_CHX10_01

GO Biological Process (7): proteolysis (GO:0006508), extracellular matrix disassembly (GO:0022617), protein catabolic process (GO:0030163), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), regulation of enamel mineralization (GO:0070173), amelogenesis (GO:0097186)

GO Molecular Function (8): metalloendopeptidase activity (GO:0004222), zinc ion binding (GO:0008270), endopeptidase activity (GO:0004175), protein binding (GO:0005515), 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
Extracellular matrix organization	2
Degradation of the extracellular matrix	1
Collagen formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
peptidase activity	2
cellular component disassembly	1
extracellular matrix organization	1
macromolecule catabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
enamel mineralization	1
regulation of tooth mineralization	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
endopeptidase activity	1
metallopeptidase activity	1
transition metal ion binding	1
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

494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP20	WDR72	Q3MJ13	968
MMP20	KLK4	Q9Y5K2	963
MMP20	ENAM	Q9NRM1	888
MMP20	AMBN	Q9NP70	885
MMP20	AMELX	Q99217	832
MMP20	AMTN	Q6UX39	782
MMP20	SACK1H	Q6ZRV2	765
MMP20	HPX	P02790	761
MMP20	ODAM	A1E959	741
MMP20	ODAPH	Q17RF5	728
MMP20	CNNM4	Q6P4Q7	717
MMP20	TUFT1	Q9NNX1	662
MMP20	DSPP	Q9NZW4	609
MMP20	DLX3	O60479	568
MMP20	DMP1	Q13316	566

IntAct

0 interactions, top by confidence:

BioGRID (9): DIABLO (Co-fractionation), FH (Co-fractionation), YWHAE (Co-fractionation), MMP24 (Negative Genetic), MMP20 (Negative Genetic), MMP20 (Negative Genetic), MMP8 (Negative Genetic), MMP20 (Affinity Capture-MS), MMP20 (Cross-Linking-MS (XL-MS))

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

Diamond homologs: 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

4 interactions.

A	Effect	B	Mechanism
MMP20	“down-regulates quantity by destabilization”	ACAN	cleavage
MMP20	up-regulates	ECM_disassembly
MMP20	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	122
Likely benign	9
Benign	50

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
139624	NM_004771.4(MMP20):c.678T>A (p.His226Gln)	Pathogenic
139625	NM_004771.4(MMP20):c.102G>A (p.Trp34Ter)	Pathogenic
189295	NM_004771.4(MMP20):c.611A>G (p.His204Arg)	Pathogenic
5428	NM_004771.4(MMP20):c.954-2A>T	Pathogenic
917991	NM_004771.4(MMP20):c.710C>A (p.Ser237Tyr)	Pathogenic
917992	NM_004771.4(MMP20):c.1122A>C (p.Gln374His)	Pathogenic
917993	NM_004771.4(MMP20):c.809_811+12delinsCCAG	Pathogenic
2445440	NM_004771.4(MMP20):c.1362C>G (p.Tyr454Ter)	Likely pathogenic
2445441	NM_004771.4(MMP20):c.359dup (p.Asn120fs)	Likely pathogenic
2445443	NM_004771.4(MMP20):c.1126C>T (p.Gln376Ter)	Likely pathogenic
4845908	NM_004771.4(MMP20):c.566T>C (p.Leu189Pro)	Likely pathogenic
917990	NM_004771.4(MMP20):c.625G>C (p.Glu209Gln)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102593500:C:G	A396P	0.999
11:102594666:C:G	A349P	0.999
11:102609058:A:C	H230Q	0.999
11:102609058:A:T	H230Q	0.999
11:102609068:T:A	E227V	0.999
11:102609921:C:A	W211C	0.999
11:102609921:C:G	W211C	0.999
11:102609923:A:G	W211R	0.999
11:102609923:A:T	W211R	0.999
11:102609975:A:C	F193L	0.999
11:102609975:A:T	F193L	0.999
11:102609977:A:G	F193L	0.999
11:102609983:G:C	H191D	0.999
11:102610008:G:C	F182L	0.999
11:102610008:G:T	F182L	0.999
11:102610010:A:G	F182L	0.999
11:102616835:C:A	W117C	0.999
11:102616835:C:G	W117C	0.999
11:102616837:A:G	W117R	0.999
11:102616837:A:T	W117R	0.999
11:102579057:C:G	A445P	0.998
11:102606578:C:G	A304P	0.998
11:102609016:C:A	M244I	0.998
11:102609016:C:G	M244I	0.998
11:102609016:C:T	M244I	0.998
11:102609040:A:C	H236Q	0.998
11:102609040:A:T	H236Q	0.998
11:102609047:A:G	L234P	0.998
11:102609060:G:C	H230D	0.998
11:102609062:C:T	G229D	0.998

dbSNP variants (sampled 300 via entrez): RS1000025386 (11:102587570 C>T), RS1000056766 (11:102587299 T>C), RS1000149537 (11:102612163 C>A,T), RS1000193351 (11:102609198 C>T), RS1000381153 (11:102601528 T>C), RS1000412233 (11:102601817 T>C), RS1000605623 (11:102596901 G>C,T), RS1000661731 (11:102577036 C>G,T), RS1000675560 (11:102595914 A>G), RS1000712164 (11:102603061 C>T), RS1000774845 (11:102576879 T>C), RS1000785684 (11:102615293 A>G), RS1000890992 (11:102623428 A>G), RS1000891056 (11:102598784 G>A,T), RS1000923497 (11:102599071 G>A,C)

Disease associations

OMIM: gene MIM:604629 | disease phenotypes: MIM:612529, MIM:181500, MIM:617854

GenCC curated gene-disease

Disease	Classification	Inheritance
amelogenesis imperfecta hypomaturation type 2A2	Strong	Autosomal recessive
amelogenesis imperfecta type 2	Supportive	Autosomal recessive

Mondo (4): amelogenesis imperfecta hypomaturation type 2A2 (MONDO:0012926), schizophrenia (MONDO:0005090), intellectual disability, autosomal dominant 56 (MONDO:0030922), amelogenesis imperfecta type 2 (MONDO:0015048)

Orphanet (2): Amelogenesis imperfecta (Orphanet:88661), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

5 total (6 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000705	Amelogenesis imperfecta
HP:0006286	Yellow-brown discoloration of the teeth
HP:0009102	Anterior open-bite malocclusion
HP:0033786	Hypomature enamel
HP:0100753	Schizophrenia

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001942_2	Prostate cancer	2.000000e-11
GCST003542_184	Night sleep phenotypes	7.000000e-07
GCST004883_1	Neuroblastoma (11q deletion)	3.000000e-10
GCST005651_6	Urinary metabolite levels in chronic kidney disease	5.000000e-08
GCST006278_1	Adverse response to antithyroid drugs in Graves disease	9.000000e-07
GCST006608_1	Response to TNF inhibitor in rheumatoid arthritis (change in patient global heath assessment score)	8.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0007838	response to anti-thyroid drug
EFO:0004653	response to TNF antagonist
EFO:0004778	self rated health

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536606	Amelogenesis Imperfecta hypomaturation type (supp.)
C567279	Amelogenesis Imperfecta, Hypomaturation Type, Iia2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938226 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,447 (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

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MARIMASTAT

PubChem BioAssay actives

1 with measured affinity, of 10 total; 1 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,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N’,3-dihydroxy-2-(2-methylpropyl)butanediamide	1274674: Inhibition of MMP20 (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 assay	ic50	10.0000	uM

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Valproic Acid	increases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1941973	Binding	Inhibition of MMP20 assessed as residual activity using Knight SSP as substrate at 100 uM after 1.5 to 4 hrs by spectrofluorometric analysis relative to control	Identification of novel, exosite-binding matrix metalloproteinase-13 inhibitor scaffolds. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety