TIMP1

Chr X

TIMP metallopeptidase inhibitor 1

Also known as: CLGI, EPA, EPO, HCI, TIMP, TIMP-1

NCBI Gene: 7076ENSG00000102265UniProt: P01033OMIM: 305370

This gene encodes TIMP1, a metalloproteinase inhibitor that forms complexes with matrix metalloproteinases to inactivate them and also functions as a growth factor regulating cell differentiation, migration and death. Mutations cause X-linked intellectual disability with seizures and spasticity, typically presenting in early childhood. The gene follows X-linked inheritance patterns, with males more severely affected than carrier females.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.78
Clinical Summary— TIMP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.17) despite low pLI — interpret in context.
📋
ClinVar Variants
48 unique Pathogenic / Likely Pathogenic· 22 VUS of 107 total submissions
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.499
Z-score 1.90
OE 0.17 (0.06–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.03Z-score
OE missense 0.69 (0.55–0.85)
58 obs / 84.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.06–0.78)
0≤0.351.4
Missense OE0.69 (0.55–0.85)
0≤0.61.4
Synonymous OE0.74
0≤1.21.6
LoF obs/exp: 1 / 6.0Missense obs/exp: 58 / 84.6Syn Z: 1.17

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic2
VUS22
Likely Benign8
Benign2
46
Pathogenic
2
Likely Pathogenic
22
VUS
8
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
2
0
2
VUS
0
16
6
0
22
Likely Benign
0
5
3
0
8
Benign
0
1
0
1
2
Total02257180

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TIMP1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrative bioinformatic analysis prioritizes TIMP1 and FN1 as angiogenesis-related candidate genes in diabetic foot ulcers.
Hu X et al.·PLoS One
2026
Nobiletin in the modified Yiqi Jianpi Decoction enhances the antitumor activity of CD8+ T cells in colorectal cancer by regulating the TIMP1/CD274 axis.
Luo L et al.·Korean J Physiol Pharmacol
2026
TIMP1 and DPP4 Promote Tumor Progression by Regulating Lactate Metabolism in Papillary Thyroid Carcinoma.
Mu S et al.·Cancers (Basel)
2026
TIMP1 promotes colorectal cancer progression through inhibition of ferroptosis via the ubiquitin-mediated regulation of NRF2.
Geng C et al.·Biochim Biophys Acta Mol Basis Dis
2026
TIMP1 and PKM drive immunosuppression and metabolic remodeling to promote colorectal cancer progression through integrated multi-omics analysis.
Wang Y et al.·Int J Biol Macromol
2026Functional
Top 5 resultsSearch Europe PMC ↗

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