TEK

Chr 9AD

TEK receptor tyrosine kinase

Also known as: CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1

NCBI Gene: 7010 ENSG00000120156 UniProt: Q02763 OMIM: 600221

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glaucoma 3, primary congenital, EMIM #617272

Venous malformations, multiple cutaneous and mucosalMIM #600195

UniProtDominantly inherited venous malformations

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · TEK-related primary glaucoma · AD · ClinGen 2022

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

213

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

📖

GeneReview available — TEK

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.18LOEUF

pLI 1.000

Z-score 6.49

OE 0.09 (0.04–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.35Z-score

OE missense 0.84 (0.78–0.91)

501 obs / 593.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.18)

0≤0.351.4

Missense OE?0.84 (0.78–0.91)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 5 / 58.6Missense obs/exp: 501 / 593.5Syn Z: -3.20

Background carrier burden — how many people carry a rare variant somewhere in TEK?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,263 rare PASS variants

Rare truncating (LoF)

1 in 3,300

93 rare PASS variants

Rare synonymous (reference)

1 in 76

601 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TEK. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 62	1 in 2,500
South Asian	~43k	1 in 57	≈ 1 in 8,800
Remaining (unassigned)	~30k	1 in 51	1 in 3,000
European (Finnish)	~27k	1 in 170	1 in 740
Admixed American	~22k	1 in 69	1 in 2,200
African / African American	~21k	1 in 41	≈ 1 in 6,000
East Asian	~20k	1 in 49	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 63	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 23 coding exons well covered in gnomAD exomes and genomes.? see exons ↓