TIMP2

Chr 17

TIMP metallopeptidase inhibitor 2

Also known as: CSC-21K, DDC8

NCBI Gene: 7077UniProt: P16035

This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

3
Active trials
0
ClinVar variants
0
Pathogenic / LP
1.6
Missense Z
0.50
LOEUF
7
Pubs (2 yr)
Clinical Summary— TIMP2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.79) — some intolerance to loss-of-function variants.
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.50LOEUF
pLI 0.789
Z-score 2.56
OE 0.11 (0.04–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.61Z-score
OE missense 0.59 (0.48–0.72)
71 obs / 120.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.04–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.48–0.72)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 1 / 9.5Missense obs/exp: 71 / 120.6Syn Z: -0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TIMP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs
Costanzo L et al.·Pulm Med
2022
The prognostic and diagnostic value of tissue inhibitor of metalloproteinases gene family and potential function in gastric cancer
Li Z et al.·J Cancer
2021
Identification of TIMP2 as a Prognostic Biomarker and Its Correlation with Tumor Immune Microenvironment: A Comprehensive Pan-Cancer Analysis
Wang DD et al.·J Oncol
2022
Timp2 loss-of-function mutation and TIMP2 treatment in murine model of NSCLC: modulation of immunosuppression and oncogenic signaling
Peeney D et al.·bioRxiv
2023Functional
Timp2 loss-of-function mutation and TIMP2 treatment in a murine model of NSCLC: Modulation of immunosuppression and oncogenic signaling
Peeney D et al.·Transl Oncol
2025Functional
Histidine Tag-Specific PEGylation Improves the Circulating Half-Life of TIMP2
Toor J et al.·ACS Appl Bio Mater
2025
NephroCheck at 10: addressing unmet needs in AKI diagnosis and risk stratification
Martin-Cleary C et al.·Clin Kidney J
2023
Dznep, a histone modification inhibitor, inhibits HIF1alpha binding to TIMP2 gene and suppresses TIMP2 expression under hypoxia
Yamazaki T et al.·Physiol Rep
2023
Effect of TIMP2/TIMP3 genes on the risk of osteosarcoma in Zhejiang population
Wu Z et al.·Medicine (Baltimore)
2021
Top 9 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Knee Osteoarthritis

Dietary Supplementation With Blueberry in OA

ACTIVE NOT RECRUITING
NCT05784545Phase NAUniversity of ExeterStarted 2023-05-22
Blueberry powder supplementMaltodextrin supplementation
Arrhythmogenic Right Ventricular Dysplasia

Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD

RECRUITING
NCT03593317Phase PHASE2Hospices Civils de LyonStarted 2024-12-20
SpironolactonePlacebo
Pelvic Organ ProlapseFemale Urogenital Diseases

Pelvic Organs Prolapse Treatment Using Neodymium Laser

ACTIVE NOT RECRUITING
NCT05000957Phase NAMeLSyTech, LtdStarted 2021-10-03
Laser TreatmentBlood analysisСlinical urine test

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients