KNG1 Gene - Kininogen 1
KNG1: A key component of the contact activation system and a precursor of bradykinin, involved in inflammation, coagulation, and vascular permeability.
Gene Information Card
| Symbol | KNG1 |
|---|---|
| Full Name | Kininogen 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 3827 ncbi.nlm.nih.gov/gene/3827 |
| Ensembl ID | ENSG00000113889 |
| UniProt ID | P01042 |
| OMIM ID | 612358 |
| HGNC ID | 6383 |
| Aliases | BDK, HMWK, KNG, KNG1_HUMAN |
Description
The KNG1 gene encodes kininogen 1, a plasma protein that exists in two forms: high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). HMWK is a critical component of the contact activation system (intrinsic coagulation pathway) and serves as a precursor for bradykinin, a potent vasoactive peptide that increases vascular permeability and mediates inflammation. LMWK is primarily involved in the generation of bradykinin in tissues. KNG1 is expressed in the liver and secreted into plasma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Kininogen deficiency (HMWK deficiency) | Loss-of-function mutations in KNG1 lead to reduced or absent HMWK, impairing contact activation and prolonging activated partial thromboplastin time (aPTT). | ClinVar, OMIM |
| Hereditary angioedema (HAE) type III (estrogen-dependent) | Gain-of-function mutations in KNG1 (e.g., p.Met379Lys) increase bradykinin production, causing recurrent episodes of swelling. | OMIM, PubMed |
| Thrombophilia | Polymorphisms in KNG1 may alter bradykinin release and coagulation balance, contributing to venous thromboembolism risk. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 58.2 | High |
| Kidney | 4.1 | Low |
| Lung | 3.5 | Low |
| Heart | 2.8 | Low |
| Brain | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 62.5 | High expression; liver-derived cell line |
| HEK 293 (embryonic kidney) | 1.2 | Low expression |
| A549 (lung carcinoma) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1136T>A (p.Met379Lys) | Missense | Rare | Gain-of-function; associated with hereditary angioedema type III |
| c.1048C>T (p.Arg350*) | Nonsense | Rare | Loss-of-function; causes kininogen deficiency |
| c.581G>A (p.Arg194His) | Missense | 0.01% (gnomAD) | Likely benign; no known disease association |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg350*) lead to truncated or absent kininogen, impairing contact activation and bradykinin generation.
Gain of Function (GOF)
Missense mutations (e.g., p.Met379Lys) enhance bradykinin release, increasing vascular permeability and causing angioedema.
Dominant Negative (DN)
No dominant-negative mutations have been reported for KNG1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Contact activation system (intrinsic coagulation pathway)
• Bradykinin/kallikrein system
• Complement and coagulation cascades (KEGG: hsa04610)
Protein Summary
Kininogen 1 (UniProt P01042) is a 626-amino acid glycoprotein synthesized in the liver. It is cleaved by plasma kallikrein to release bradykinin (a nonapeptide) from its internal domain. HMWK (120 kDa) contains six domains: D1 (calcium binding), D2 and D3 (cysteine protease inhibitors), D4 (bradykinin), D5 (histidine-rich region for surface binding), and D6 (prekallikrein and factor XI binding). LMWK (68 kDa) lacks D5 and D6. The protein is essential for contact activation, fibrinolysis, and inflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KNG1 Knockout HEK293 Cell Line | EDJ-KQ1749 | Human | 3827 | Details Get a Quote |
| KNG1 Knockout HeLa Cell Line | EDJ-KQ53748 | Human | 3827 | Details Get a Quote |
| KNG1 Knockout A-549 Cell Line | EDJ-KQ62225 | Human | 3827 | Details Get a Quote |
| KNG1 Knockout HCT 116 Cell Line | EDJ-KQ70709 | Human | 3827 | Details Get a Quote |
