TIMP3

Chr 22q12.3

TIMP metallopeptidase inhibitor 3

MANE:: ENST00000266085.7

OMIM: 188826 ↗NCBI: 7078 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

TIMP3 · P35625

v62025-08-01

Predicted Aligned Error matrix for TIMP3 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

87.0/ 100

Confident

211 residues

Confidence breakdown

Very high(≥ 90)75%
Confident(70–90)6%
Low(50–70)11%
Very low(< 50)8%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Retinal disorders
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Glaucoma (developmental)
Structural eye disease
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

Sorsby fundus dystrophy
0.77
Sorsby's fundus dystrophy
0.53
Retinal dystrophy
0.52
venous thromboembolism
0.43
open-angle glaucoma
0.42
glaucoma
0.42
retinal disorder
0.41
acne
0.41
eye disorder
0.37
cutaneous lupus erythematosus
0.29

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Metalloproteinase inhibitor 3

Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs). Regulates extracellular matrix (ECM) remodeling through inhibition of matrix metalloproteinases (MMP) including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15. Additionally, modulates the processing of amyloid precursor protein (APP) and apolipoprotein E receptor ApoER2 by inhibiting two alpha-secretases ADAM10 and ADAM17 (PubMed:17913923). Functions as a tumor suppressor and a potent inhibitor of angiogenesis. Exerts its anti-angiogenic effect by directly interacting with vascular endothelial growth factor (VEGF) receptor-2/KDR, preventing its binding to the VEGFA ligand (PubMed:12652295). Selectively induces apoptosis in angiogenic endothelial cells through a caspase-independent cell death pathway (PubMed:25558000). Mechanistically, inhibits matrix-induced focal adhesion kinase PTK2 tyrosine phosphorylation and association with paxillin/PXN and disrupts the incorporation of ITGB3, PTK2 and PXN into focal adhesion contacts on the matrix (PubMed:25558000)