TIE1

Chr 1AD

tyrosine kinase with immunoglobulin like and EGF like domains 1

ENSG00000066056UniProt: P35590

Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis

Primary Disease Associations & Inheritance

Lymphatic malformation 11MIM #619401
AD
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TIE1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.89LOEUF
pLI 0.000
Z-score 2.27
OE 0.68 (0.52–0.89)
Tolerant

Typical tolerance to LoF variation

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.
1.51Z-score
OE missense 0.84 (0.79–0.90)
615 obs / 729.9 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.0.68 (0.52–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.79–0.90)
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.0.89
0≤1.21.6
LoF obs/exp: 39 / 57.6Missense obs/exp: 615 / 729.9Syn Z: 1.53

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TIE1 · 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

Lymphatic malformation 11

MIM #619401

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss-of-function mutations of the TIE1 receptor tyrosine kinase cause late-onset primary lymphedema.
Brouillard P et al.·J Clin Invest
2024
Investigation into the genetics of fetal congenital lymphatic anomalies.
Rogerson D et al.·Prenat Diagn
2023
TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study.
Rajasundaram S et al.·J Transl Med
2023
Mendelian Randomization Using the Druggable Genome Reveals Genetically Supported Drug Targets for Psychiatric Disorders.
Li X et al.·Schizophr Bull
2023
The Ets2 super-enhancer modulates endothelial-mesenchymal transition during cardiac ageing.
Guo Z et al.·Cardiovasc Res
2026
The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseases.
Zhu S et al.·J Cell Physiol
2022Review
FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway.
Chen E et al.·J Transl Med
2023
Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody.
Singhal M et al.·EMBO Mol Med
2020
Cervical cancer cell-derived Tie1 expression via PI3K/AKT signaling pathway promotes tumor progression.
Wei Y et al.·Exp Cell Res
2024
Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL).
Aguayo A et al.·Leuk Res
2001
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools