TEK
Chr 9ADTEK receptor tyrosine kinase
Also known as: CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1
The TEK protein is a tyrosine kinase receptor that binds angiopoietins to regulate angiogenesis, endothelial cell functions, and vascular development during embryogenesis and throughout life. Mutations cause autosomal dominant venous malformations of the skin and mucous membranes, and primary congenital glaucoma. This gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.179), reflecting its essential role in vascular development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
483 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 14 | 7 | 48 | 0 | 69 |
Likely Pathogenic | 28 | 10 | 4 | 0 | 42 |
VUS | 1 | 165 | 20 | 5 | 191 |
Likely Benign | 0 | 15 | 13 | 25 | 53 |
Benign | 0 | 8 | 79 | 16 | 103 |
Conflicting | — | 7 | |||
| Total | 43 | 205 | 164 | 46 | 465 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TEK · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Nirogacestat in Patients With Kaposi Sarcoma
NOT YET RECRUITINGMitoQ for Early-phase Schizophrenia-spectrum Disorder and Mitochondrial Dysfunction
RECRUITINGExternal Resources
Links to major genomics databases and tools