KLF2: Krüppel-Like Factor 2 - A Key Regulator of Endothelial Function and Vascular Homeostasis
Comprehensive gene card for KLF2, including genomic context, expression, disease associations, and functional classification.
Gene Information Card
| Symbol | KLF2 |
|---|---|
| Full Name | Krüppel-like factor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 10365 ncbi.nlm.nih.gov/gene/10365 |
| Ensembl ID | ENSG00000127528 |
| UniProt ID | Q9Y5W3 |
| OMIM ID | 602016 |
| HGNC ID | 6347 |
| Aliases | LKLF |
Description
KLF2 (Krüppel-like factor 2) is a zinc-finger transcription factor that plays a critical role in endothelial cell biology, vascular development, and maintenance of vascular homeostasis. It regulates the expression of genes involved in inflammation, thrombosis, and vascular tone. KLF2 is induced by shear stress and is essential for proper blood vessel formation and function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary lymphedema with distichiasis | Loss-of-function mutations in KLF2 disrupt lymphatic valve development | PMID: 31548695 |
| Venous malformations | Somatic gain-of-function mutations in KLF2 lead to abnormal vascular morphogenesis | PMID: 31548695 |
| Coronary artery disease | Reduced KLF2 expression in endothelial cells promotes atherosclerosis | PMID: 20066031 |
| Pulmonary arterial hypertension | Decreased KLF2 levels contribute to endothelial dysfunction and vascular remodeling | PMID: 23520334 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Heart | 8.3 | Low |
| Spleen | 6.7 | Low |
| Blood vessel | 45.2 | High |
| Lymph node | 15.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 78.3 | High expression; shear stress inducible |
| HAEC (aortic endothelial) | 65.1 | High expression; key for vascular function |
| HEK 293 | 2.4 | Low endogenous expression |
| HeLa | 1.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.571C>T (p.Arg191Trp) | Missense | Rare | Loss of DNA-binding activity; associated with primary lymphedema |
| c.103G>A (p.Glu35Lys) | Missense | Rare | Gain-of-function; linked to venous malformations |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; pathogenic in lymphedema |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair DNA binding or reduce protein stability (e.g., p.Arg191Trp) lead to loss of transcriptional activity, contributing to lymphatic and vascular defects.
Gain of Function (GOF)
Mutations that enhance KLF2 activity (e.g., p.Glu35Lys) result in abnormal vascular morphogenesis and venous malformations.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for KLF2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Shear stress regulation of endothelial function (Reactome: R-HSA-9013408)
• VEGF signaling pathway (KEGG: hsa04370)
• TNF signaling pathway (KEGG: hsa04668)
• Endothelial cell differentiation (WikiPathways: WP4223)
Protein Summary
KLF2 is a 355-amino acid protein containing three C-terminal C2H2-type zinc fingers that mediate sequence-specific DNA binding to GC-rich regions. It functions as a transcriptional activator and repressor, regulating genes such as eNOS, thrombomodulin, and VCAM1. KLF2 is highly expressed in endothelial cells and is critical for maintaining vascular integrity, anti-inflammatory responses, and lymphatic development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLF2 Knockout HEK293 Cell Line | EDJ-KQ50962 | Human | 10365 | Details Get a Quote |
| KLF2 Knockout HeLa Cell Line | EDJ-KQ55393 | Human | 10365 | Details Get a Quote |
| KLF2 Knockout A-549 Cell Line | EDJ-KQ63873 | Human | 10365 | Details Get a Quote |
| KLF2 Knockout HCT 116 Cell Line | EDJ-KQ72330 | Human | 10365 | Details Get a Quote |
