TIMP4: Tissue Inhibitor of Metalloproteinase 4
A key regulator of extracellular matrix remodeling and tumor suppression
Gene Information Card
| Symbol | TIMP4 |
|---|---|
| Full Name | Tissue Inhibitor of Metalloproteinase 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 3p25.2 |
| NCBI Gene ID | 7079 ncbi.nlm.nih.gov/gene/7079 |
| Ensembl ID | ENSG00000157110 |
| UniProt ID | Q99727 |
| OMIM ID | 601915 |
| HGNC ID | 11823 |
| Aliases | TIMP-4, TIMP4_HUMAN |
Description
TIMP4 encodes a member of the tissue inhibitor of metalloproteinase (TIMP) family. The protein inhibits matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase (ADAM) enzymes, thereby regulating extracellular matrix turnover, cell migration, and tissue remodeling. TIMP4 is expressed in heart, brain, ovary, and skeletal muscle, and its dysregulation is implicated in cancer progression, cardiovascular diseases, and fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Reduced TIMP4 expression correlates with increased MMP activity and tumor invasion | PMID: 12058030 |
| Ovarian cancer | TIMP4 overexpression in tumor stroma promotes angiogenesis and metastasis | PMID: 15604238 |
| Cardiovascular disease | TIMP4 deficiency leads to adverse cardiac remodeling and fibrosis | PMID: 20881019 |
| Osteoarthritis | Altered TIMP4 levels contribute to cartilage degradation | PMID: 11500891 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Low |
| Ovary | 15.2 | Medium |
| Skeletal muscle | 10.1 | Low |
| Kidney | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 5.4 | Low expression |
| SKOV3 (ovarian cancer) | 18.9 | High expression |
| HUVEC (endothelial) | 9.2 | Moderate expression |
| HeLa (cervical cancer) | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3G>A (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.214C>T (p.Arg72Trp) | Missense | <0.01% | Unknown functional impact |
| c.455G>A (p.Arg152Gln) | Missense | <0.01% | Reported in ClinVar as uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TIMP4 are rare but may lead to increased MMP activity and altered ECM remodeling.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Matrix metalloproteinase inhibition (Reactome: R-HSA-1592389)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
• Degradation of the extracellular matrix (Reactome: R-HSA-1474228)
Protein Summary
TIMP4 is a 224-amino-acid secreted protein containing an N-terminal domain that binds the active site of MMPs and a C-terminal domain that mediates interactions with pro-MMPs. It inhibits MMP-1, -2, -3, -7, -9, and -13, as well as ADAM17. TIMP4 is unique among TIMPs for its restricted tissue distribution and its role in modulating angiogenesis and tumor growth.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TIMP4 Knockout HEK293 Cell Line | EDJ-KQ5931 | Human | 7079 | Details Get a Quote |
| TIMP4 Knockout A-549 Cell Line | EDJ-KQ29475 | Human | 7079 | Details Get a Quote |
| TIMP4 Knockout HeLa Cell Line | EDJ-KQ29476 | Human | 7079 | Details Get a Quote |
| TIMP4 Knockout HCT 116 Cell Line | EDJ-KQ71616 | Human | 7079 | Details Get a Quote |
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