MMP19

Summary

MMP19 (matrix metallopeptidase 19, HGNC:7165) is a protein-coding gene on chromosome 12q13.2, encoding Matrix metalloproteinase-19 (Q99542). Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease).

This gene encodes a member of a family of proteins that 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 protein is secreted as an inactive proprotein, which is activated upon cleavage by extracellular proteases. Alternative splicing results in multiple transcript variants for this gene.

Source: NCBI Gene 4327 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial cavitary optic disk anomaly (Supportive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 99 total — 2 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_002429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7165
Approved symbol	MMP19
Name	matrix metallopeptidase 19
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	RASI-1
Ensembl gene	ENSG00000123342
Ensembl biotype	protein_coding
OMIM	601807
Entrez	4327

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000322569, ENST00000409200, ENST00000547299, ENST00000547487, ENST00000547685, ENST00000548629, ENST00000548882, ENST00000552763, ENST00000552872, ENST00000889539, ENST00000889540, ENST00000889541, ENST00000913023, ENST00000956503, ENST00000956504, ENST00000956505

RefSeq mRNA: 3 — MANE Select: NM_002429 NM_001272101, NM_001414375, NM_002429

CCDS: CCDS61146, CCDS8895

Canonical transcript exons

ENST00000322569 — 9 exons

Exon	Start	End
ENSE00001611990	55841106	55841236
ENSE00001736596	55838606	55838734
ENSE00002206938	55842744	55842936
ENSE00003537865	55840667	55840882
ENSE00003562439	55837843	55838007
ENSE00003613282	55842353	55842438
ENSE00003627980	55835433	55837374
ENSE00003635532	55837555	55837682
ENSE00003641982	55839496	55839741

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1837 / max 371.7148, expressed in 1020 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131444	6.4424	704
131445	3.3911	928
131443	0.3502	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	96.44	gold quality
gall bladder	UBERON:0002110	94.77	gold quality
omental fat pad	UBERON:0010414	94.44	gold quality
peritoneum	UBERON:0002358	94.40	gold quality
olfactory bulb	UBERON:0002264	94.04	silver quality
adipose tissue of abdominal region	UBERON:0007808	93.21	gold quality
upper lobe of left lung	UBERON:0008952	92.88	gold quality
spleen	UBERON:0002106	92.87	gold quality
ascending aorta	UBERON:0001496	92.72	gold quality
thoracic aorta	UBERON:0001515	92.69	gold quality
stromal cell of endometrium	CL:0002255	92.64	gold quality
descending thoracic aorta	UBERON:0002345	92.50	gold quality
upper lobe of lung	UBERON:0008948	92.28	gold quality
smooth muscle tissue	UBERON:0001135	91.89	gold quality
right ovary	UBERON:0002118	91.32	gold quality
mucosa of stomach	UBERON:0001199	91.01	gold quality
type B pancreatic cell	CL:0000169	90.97	gold quality
decidua	UBERON:0002450	90.40	gold quality
body of uterus	UBERON:0009853	90.21	gold quality
right lung	UBERON:0002167	89.05	gold quality
vermiform appendix	UBERON:0001154	88.96	gold quality
left coronary artery	UBERON:0001626	88.59	gold quality
caecum	UBERON:0001153	88.52	gold quality
left ovary	UBERON:0002119	88.48	gold quality
coronary artery	UBERON:0001621	88.37	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.33	gold quality
right coronary artery	UBERON:0001625	88.23	gold quality
myometrium	UBERON:0001296	88.06	gold quality
adipose tissue	UBERON:0001013	87.88	gold quality
superficial temporal artery	UBERON:0001614	87.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	3229.43
E-MTAB-6142	no	93.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU2F3, POU3F1

miRNA regulators (miRDB)

62 targeting MMP19, 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-4682	100.00	68.89	1258
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6829-5P	98.86	65.12	1480

Literature-anchored findings (GeneRIF, showing 31)

• MMP-19 is expressed by myeloid cells in an adhesion-dependent manner and associates with the cell surface by an interaction with the hemopexin-like domain. (PMID:11801661)
• Downregulation of MMP-19 expression in the epidermis is associated with transformation and histologic dedifferentiation in skin neoplasms (PMID:12516088)
• MMP-19 is a likely candidate to be the major IGFBP-3 degrading MMP (PMID:12937269)
• the importance of MMP19 as a predictor of secondary Extramammary Paget’s disease or the putative origin of Paget’s cells from the dermal adenocarcinoma cells of apocrine duct origin (PMID:15239678)
• MMP-19 actively participates in the early stages of SCC invasion. (PMID:15868410)
• Our results suggest that Tst-1 and Skn-1a regulate expression of MMPs in keratinocytes and effect both the expression and activation of these proteolytic enzymes. (PMID:17195013)
• Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy. (PMID:17980449)
• MMP-19 may have a role in tumor invasiveness in patients with oropharyngeal squamous cell carcinoma (PMID:18161657)
• the increase of MMP19 expression hallmarks the progression of cutaneous melanoma (PMID:20098411)
• Taken together, these results indicate that MMP19 is highly expressed in proliferating astrocytoma/glioma cells, and that its expression may facilitate their invasion through brain extracellular matrix components. (PMID:20142769)
• vascular MMP-19 expression significantly associated with Cerebral amyloid angiopathy–associated intracerebral haemorrhage (PMID:21261556)
• MMP-19 processes human plasminogen in a characteristic cleavage pattern to generate three angiostatin-like fragments (PMID:21787393)
• MMP-15 and MMP-19 are upregulated during colorectal tumorigenesis (PMID:22576687)
• These findings indicated for the first time that the co-expression of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma patients (PMID:22855183)
• Up-regulation of matrix metalloproteinase-19 (MMP19) induced by lung injury may play a protective role in the development of fibrosis through the induction of prostaglandin-endoperoxide synthase 2 (PTGS2). (PMID:22859522)
• ASNS and MMP19, along with eIF3a, are the sensitivity factors for cisplatin treatment and may serve as potential candidate molecular markers for predicting cisplatin sensitivity of advanced nasopharyngeal carcinoma. (PMID:23956056)
• The expression of MMP-19 in the main forms of gastrointestinal diseases, was analysed. (PMID:25056434)
• Matrix metalloproteinase-19 in lung epithelial cells stimulates proliferation and cell migration. Read More: http://www.atsjournals.org/doi/full/10.1164/rccm.201310-1903OC (PMID:25250855)
• Triplication of an enhancer may lead to overexpression of MMP19 in the optic nerve that causes cavitary optic disc anomaly. (PMID:25581579)
• the intima+media of IPAH vessels, collagens (COL4A5, COL14A1, and COL18A1), matrix metalloproteinase (MMP) 19, and a disintegrin and metalloprotease (ADAM) 33 were higher expressed, whereas MMP10, ADAM17, TIMP1, and TIMP3 were less abundant. (PMID:25840998)
• Loss of NDRG2 induced the expression of matrix metalloproteinase-19 (MMP-19), which regulated the expression of Slug at the transcriptional level in the epithelial-mesenchymal transition of gallbladder carcinoma cells. (PMID:26292259)
• the downregulation of MMP19 following respiratory syncytial virus infection may be associated with the development of airway hyperresponsiveness. (PMID:26548962)
• Levels of matrix metalloproteinases MMP-19 and MMP-20 expression are significantly increased in pancreatic ductal adenocarcinoma (PDAC). (PMID:26692439)
• transcriptional target of ligand-bound activated estrogen receptor beta acting on a specificity protein-1 binding site (PMID:26700939)
• MiR-193b-3p is an important regulator of MMP-19 in human chondrocytes and may relieve the inflammatory response in OA. (PMID:29323744)
• Study found that the expression of MMP19 was upregulated in colorectal cancer (CRC). High expression of MMP19 was determined to be an independent and poor prognostic factor in CRC. These results suggest that MMP19 may be a good biomarker for CRC. (PMID:31088409)
• MicroRNA-16 inhibits the proliferation, migration and invasion of non-small cell lung carcinoma cells by down-regulating matrix metalloproteinase-19 expression. (PMID:31298377)
• Long noncoding RNA ZEB1-AS1 affects paclitaxel and cisplatin resistance by regulating MMP19 in epithelial ovarian cancer cells. (PMID:33151424)
• Potential novel markers in IBD and CRC diagnostics. Are MMP-19 and RAGE promising candidates? (PMID:35352707)
• Endothelial cell-derived MMP19 promotes pulmonary fibrosis by inducing E(nd)MT and monocyte infiltration. (PMID:36915092)
• MMP19 Variants in Familial and Sporadic Idiopathic Pulmonary Fibrosis. (PMID:37971547)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmp19	ENSDARG00000091557
mus_musculus	Mmp19	ENSMUSG00000025355
rattus_norvegicus	Mmp19	ENSRNOG00000006778
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-19 — Q99542 (reviewed: Q99542)

Alternative names: Matrix metalloproteinase RASI, Matrix metalloproteinase-18

All UniProt accessions (4): A6ND33, B4DNP3, Q99542, F8W1C3

UniProt curated annotations — full annotation on UniProt →

Function. Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis. Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in mammary gland, placenta, lung, pancreas, ovary, small intestine, spleen, thymus, prostate, testis colon, heart and blood vessel walls. Not detected in brain and peripheral blood leukocytes. Also expressed in the synovial fluid of normal and rheumatoid patients.

Post-translational modifications. Activated by autolytic cleavage after Lys-97. Tyrosine phosphorylated by PKDCC/VLK.

Disease relevance. Cavitary optic disc anomalies (CODA) [MIM:611543] An ocular disease characterized by a profound excavation of the optic nerve. Clinical phenotype is variable and includes congenitally excavated optic nerves as well as other features of optic pit, optic nerve coloboma, and morning glory disk anomaly. Patients with CODA have a strong predilection for retinal detachment and/or separation of the retinal layers (retinoschisis) that lead to profound central vision loss. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Strongly inhibited by TIMP-2, TIMP-3 and TIMP-4, while TIMP-1 is less efficient.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Miscellaneous. Autoantigen anti-MMP19 are frequent in RA patients. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase M10A family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q99542-1	1, RASI-1, RASI-11	yes
Q99542-3	2, RASI-9
Q99542-4	3, RASI-6
Q99542-5	4

RefSeq proteins (3): NP_001259030, NP_001401304, NP_002420* (*=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
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

UniProt features (31 total): splice variant 7, binding site 4, sequence variant 4, repeat 4, mutagenesis site 2, signal peptide 1, propeptide 1, active site 1, glycosylation site 1, disulfide bond 1, chain 1, sequence conflict 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99542-F1	79.70	0.43

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): 213

Ligand- & substrate-binding residues (4): 85 (in inhibited form); 212; 216; 222

Disulfide bonds (1): 289–472

Glycosylation sites (1): 464

Mutagenesis-validated functional residues (2):

Position	Phenotype
88	reduced autolysis rate.
90	reduced autolysis rate.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 208 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_516, WALLACE_PROSTATE_CANCER_RACE_UP, CHIBA_RESPONSE_TO_TSA_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, TTGGGAG_MIR150, AGGCACT_MIR5153P, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_OVARIAN_FOLLICLE_DEVELOPMENT, ACCAATC_MIR509, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_OVULATION_CYCLE_PROCESS, GOBP_RESPONSE_TO_CAMP, GOBP_OVULATION, BACH2_01

GO Biological Process (11): angiogenesis (GO:0001525), ovarian follicle development (GO:0001541), ovulation from ovarian follicle (GO:0001542), luteolysis (GO:0001554), proteolysis (GO:0006508), response to hormone (GO:0009725), extracellular matrix disassembly (GO:0022617), cell differentiation (GO:0030154), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574), response to cAMP (GO:0051591)

GO Molecular Function (7): metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
female gonad development	3
ovulation cycle process	2
endopeptidase activity	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
anatomical structure development	1
ovulation	1
protein metabolic process	1
response to endogenous stimulus	1
response to chemical	1
cellular component disassembly	1
extracellular matrix organization	1
cellular developmental process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
metallopeptidase activity	1
serine-type peptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP19	FURIN	P09958	580
MMP19	MMP23B	O75900	496
MMP19	TIMP1	P01033	463
MMP19	TIMP2	P16035	456
MMP19	MMP14	P50281	452
MMP19	MMP17	Q9ULZ9	451
MMP19	GRN	P23781	436
MMP19	TIMP3	P35625	415
MMP19	TIMP4	Q99727	410
MMP19	DNAJC14	Q6Y2X3	394
MMP19	HPX	P02790	391
MMP19	FMOD	Q06828	360
MMP19	ADAMTS4	O75173	343
MMP19	ADAMTS15	Q8TE58	317
MMP19	CACUL1	Q86Y37	311

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MMP19	COCH	psi-mi:“MI:0914”(association)	0.350
MMP19	cidA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): COCH (Affinity Capture-MS), TTC19 (Affinity Capture-MS), FKBP7 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), CD109 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SERPINF1 (Affinity Capture-MS), MMP19 (Affinity Capture-MS)

ESM2 similar proteins: A2AX52, A6H584, A6NMZ7, A6X935, A8TX70, E1BMV3, E7FF10, O00339, O02668, O08746, O55123, O89029, P05099, P06681, P12111, P15989, P19823, P19827, P21180, P21941, P51942, P79263, P97278, P97279, Q0IIH7, Q0V8T0, Q0V8T5, Q0V8T6, Q0V8T7, Q0VCM5, Q14624, Q21540, Q29052, Q3SYW2, Q3T052, Q5GFL6, Q61702, Q61703, Q6DCQ6, Q70UZ7

Diamond homologs: A0A0N9E2K8, D0EM77, G5EBU3, O04529, O54732, O55761, O75900, O88272, O88676, O93470, P04004, P22458, P22757, P41245, P48819, P50280, P51511, P53690, P55032, Q02853, Q10739, Q196W5, Q2TBM7, Q499S5, Q5XF51, Q8K3F2, Q8N119, Q90YC2, Q99542, Q9NRE1, O13065, O18733, O18767, O18927, O23507, O35548, O44836, O55123, O60882, O62806

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MMP19	“down-regulates quantity by destabilization”	ACAN	cleavage
MMP19	up-regulates	ECM_disassembly
MMP19	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	71
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
180748	GRCh38/hg38 12q13.2(chr12:55845043-55851177)x4	Pathogenic
208981	GRCh38/hg38 12q13.2(chr12:55845043-55851177)	Pathogenic

SpliceAI

1561 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55837373:CC:C	acceptor_gain	1.0000
12:55837374:CC:C	acceptor_gain	1.0000
12:55837390:G:C	acceptor_gain	1.0000
12:55839621:A:AC	donor_gain	1.0000
12:55839622:C:CC	donor_gain	1.0000
12:55839624:T:TA	donor_gain	1.0000
12:55839738:CTCC:C	acceptor_gain	1.0000
12:55840695:CGAG:C	donor_gain	1.0000
12:55842348:CTCA:C	donor_loss	1.0000
12:55842349:TCA:T	donor_loss	1.0000
12:55842350:CA:C	donor_loss	1.0000
12:55842351:ACC:A	donor_loss	1.0000
12:55837294:C:CT	acceptor_gain	0.9900
12:55837294:C:T	acceptor_gain	0.9900
12:55837372:GCC:G	acceptor_gain	0.9900
12:55837373:CCC:C	acceptor_gain	0.9900
12:55837375:C:CC	acceptor_gain	0.9900
12:55837376:T:A	acceptor_loss	0.9900
12:55837381:A:C	acceptor_gain	0.9900
12:55837386:A:AC	acceptor_gain	0.9900
12:55837386:A:C	acceptor_gain	0.9900
12:55837390:G:GC	acceptor_gain	0.9900
12:55837841:AC:A	donor_gain	0.9900
12:55837842:CC:C	donor_gain	0.9900
12:55838020:G:GC	acceptor_gain	0.9900
12:55838022:G:GC	acceptor_gain	0.9900
12:55838027:A:T	acceptor_gain	0.9900
12:55839489:GACT:G	donor_loss	0.9900
12:55839490:ACTG:A	donor_loss	0.9900
12:55839491:CTGA:C	donor_loss	0.9900

AlphaMissense

3296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55839674:C:A	W196C	0.995
12:55839674:C:G	W196C	0.995
12:55840713:G:C	F158L	0.995
12:55840713:G:T	F158L	0.995
12:55840715:A:G	F158L	0.995
12:55840875:C:A	W104C	0.995
12:55840875:C:G	W104C	0.995
12:55840678:A:C	F170C	0.994
12:55840779:C:A	W136C	0.994
12:55840779:C:G	W136C	0.994
12:55837888:C:G	A339P	0.993
12:55839572:C:A	M230I	0.993
12:55839572:C:G	M230I	0.993
12:55839572:C:T	M230I	0.993
12:55839628:G:C	H212D	0.993
12:55839634:C:G	A210P	0.993
12:55840677:A:C	F170L	0.993
12:55840677:A:T	F170L	0.993
12:55840679:A:G	F170L	0.993
12:55839523:C:G	D247H	0.992
12:55839596:G:C	H222Q	0.992
12:55839596:G:T	H222Q	0.992
12:55839606:C:T	G219E	0.992
12:55839623:T:A	E213D	0.992
12:55839623:T:G	E213D	0.992
12:55839693:A:G	F190S	0.992
12:55839676:A:G	W196R	0.991
12:55839676:A:T	W196R	0.991
12:55840781:A:G	W136R	0.991
12:55840781:A:T	W136R	0.991

dbSNP variants (sampled 300 via entrez): RS1000296454 (12:55836413 G>C), RS1000966601 (12:55842949 G>C), RS1001068529 (12:55836749 T>C), RS1001145337 (12:55843604 A>G), RS1001637184 (12:55842776 G>A,T), RS1001733907 (12:55842311 T>G), RS1002002819 (12:55842551 T>C,G), RS1002078202 (12:55842612 G>A), RS1002681328 (12:55844111 A>C), RS1004088426 (12:55841373 C>T), RS1004140739 (12:55840960 T>TC), RS1004530126 (12:55843989 A>G), RS1005055535 (12:55835899 C>T), RS1005095691 (12:55842815 G>A,C), RS1005144769 (12:55842625 G>A,T)

Disease associations

OMIM: gene MIM:601807 | disease phenotypes: MIM:611543, MIM:178500

GenCC curated gene-disease

Disease	Classification	Inheritance
familial cavitary optic disk anomaly	Supportive	Autosomal dominant

Mondo (2): familial cavitary optic disk anomaly (MONDO:0012687), interstitial lung disease 2 (MONDO:0800497)

Orphanet (3): Familial cavitary optic disc anomaly (Orphanet:464760), Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000662	Nyctalopia
HP:0001123	Visual field defect
HP:0007663	Reduced visual acuity
HP:0500087	Peripapillary atrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003219_5	Advanced age-related macular degeneration	4.000000e-09
GCST010002_217	Refractive error	6.000000e-174

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566924	Cavitary Optic Disc Anomalies (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938214 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M10: Matrix metallopeptidase

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases mutagenesis	4
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	increases expression, decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Zinc	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
sotorasib	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
tri-o-cresyl phosphate	increases expression	1
triadimefon	decreases expression	1
abrine	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, affects expression	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Calcitriol	decreases expression	1
Dexamethasone	decreases expression, affects expression, affects cotreatment, increases expression	1
Hydrogen Peroxide	decreases expression	1
Indomethacin	affects cotreatment, increases expression, decreases expression, affects expression	1
Nickel	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1

ChEMBL screening assays

4 unique, capped per target: 2 admet, 1 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1943056	Binding	Inhibition of MMP19 using Mca-Pro-cyclohexyl-Ala-Gly-Nva-His-Ala- Dap(Dnp)-NH2 as substrate by fluorometric analysis	Lead optimisation of selective non-zinc binding inhibitors of MMP13. Part 2. — Bioorg Med Chem Lett
CHEMBL4670430	ADMET	Covalent inhibition of MMP19 (unknown origin) at 25 uM using TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6’-TAMRA)-Ala-Lys-NH2 as substrate preincubated with enzyme for 30 mins followed by substrate addition by fluorescence assay	Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A. — J Med Chem
CHEMBL6139248	Toxicity	Inhibition of MMP-19 (unknown origin) at 25 uM	Bifunctional Inhibition of Botulinum Neurotoxin A Protease: Unexpected Active Site Inhibition Enhances Covalent Targeting of an Allosteric Site. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06372353	Not specified	COMPLETED	The Effect Of Baduanjin Exercises In Patients With Idiopathic Pulmonary Fibrosis
NCT06644144	Not specified	RECRUITING	P4O2 ILD Extension