KNG1 kininogen 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KNG1provided by HGNC
Official Full Name: kininogen 1provided by HGNC
Primary source: HGNC:HGNC:6383
See related: Ensembl:ENSG00000113889 MIM:612358; AllianceGenome:HGNC:6383
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BK; HK; BDK; KNG; HAE6; HMWK
Summary: This gene uses alternative splicing to generate two different proteins- high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). HMWK is essential for blood coagulation and assembly of the kallikrein-kinin system. Also, bradykinin, a peptide causing numerous physiological effects, is released from HMWK. Bradykinin also functions as an antimicrobial peptide with antibacterial and antifungal activity. In contrast to HMWK, LMWK is not involved in blood coagulation. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reduces or depletes angiotensin converting enzyme 2 (ACE2), which results in an increase in levels of des-Arg(9)-bradykinin, a bioactive metabolite of bradykinin that is associated with lung injury and inflammation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Restricted expression toward liver (RPKM 432.8) See more
Orthologs: mouse all
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Genomic context

Location:: 3q27.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (186717359..186744410)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (189539122..189566165)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (186435148..186462199)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons.
Title: Bradykinin receptor expression and bradykinin-mediated sensitization of human sensory neurons.
An HBV susceptibility variant of KNG1 modulates the therapeutic effects of interferons alpha and lambda1 in HBV infection by promoting MAVS lysosomal degradation.
Title: An HBV susceptibility variant of KNG1 modulates the therapeutic effects of interferons α and λ1 in HBV infection by promoting MAVS lysosomal degradation.
High preoperative bradykinin level is a risk factor for severe postoperative hypoxaemia in acute aortic dissection surgery.
Title: High preoperative bradykinin level is a risk factor for severe postoperative hypoxaemia in acute aortic dissection surgery.
gC1qR Antibody Can Modulate Endothelial Cell Permeability in Angioedema.
Title: gC1qR Antibody Can Modulate Endothelial Cell Permeability in Angioedema.
Plasmin-mediated cleavage of high-molecular-weight kininogen contributes to acetaminophen-induced acute liver failure.
Title: Plasmin-mediated cleavage of high-molecular-weight kininogen contributes to acetaminophen-induced acute liver failure.
Kininogen supports inflammation and bacterial spreading during Streptococccus Pyogenes Sepsis.
Title: Kininogen supports inflammation and bacterial spreading during Streptococccus Pyogenes Sepsis.
Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson's Disease.
Title: Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson's Disease.
Bradykinin stimulates prostaglandin E2 release in human skeletal muscular fibroblasts.
Title: Bradykinin stimulates prostaglandin E(2) release in human skeletal muscular fibroblasts.
Pathways for bradykinin formation and interrelationship with complement as a cause of edematous lung in COVID-19 patients.
Title: Pathways for bradykinin formation and interrelationship with complement as a cause of edematous lung in COVID-19 patients.
Bradykinin and oxidative stress in patients with hereditary angioedema due to C1 inhibitor deficiency.
Title: Bradykinin and oxidative stress in patients with hereditary angioedema due to C1 inhibitor deficiency.

Submit: New GeneRIF Correction See all GeneRIFs (92)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Angioedema, hereditary, 6 MedGen: C5543516 OMIM: 619363 GeneReviews: Not available	Compare labs
High molecular weight kininogen deficiency MedGen: C0272340 OMIM: 228960 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M11437 (e-PCR)
- UniSTS:11530

RH102978 (e-PCR)
- UniSTS:97312

GDB:181214 (e-PCR)
- UniSTS:155182

SHGC-35523 (e-PCR)
- UniSTS:17812

D3S3899 (e-PCR)
- UniSTS:77486

D3S3935 (e-PCR)
- UniSTS:30166

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables heparin binding	NAS Non-traceable Author Statement more info	PubMed
enables hormone activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IDA Inferred from Direct Assay more info	PubMed
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in killing of cells of another organism	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of blood coagulation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in vasodilation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	HDA more info	PubMed
is_active_in extracellular region	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: kininogen-1

Names: alpha-2-thiol proteinase inhibitor; bradykinin; fitzgerald factor; high molecular weight kininogen; williams-Fitzgerald-Flaujeac factor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016009.1 RefSeqGene

Range

5051..32102

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_598

mRNA and Protein(s)

NM_000893.4 → NP_000884.1 kininogen-1 isoform 2 precursor

See identical proteins and their annotated locations for NP_000884.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice pattern in the 3' coding region, compared to variant 1. The resulting isoform (2), also known as low molecular weight preprokininogen, has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC109780, AC112907, DC362362, K02566

Consensus CDS

CCDS3281.1

UniProtKB/TrEMBL

B4DPP8, E9PEA0

Related

ENSP00000287611.2, ENST00000287611.8

Conserved Domains (1) summary

pfam00031
Location:266 → 360

Cystatin; Cystatin domain
NM_001102416.3 → NP_001095886.1 kininogen-1 isoform 1 precursor

See identical proteins and their annotated locations for NP_001095886.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1), also known as high molecular weight preprokininogen.

Source sequence(s)

AC109780, AC112907, DC362362, K02566

Consensus CDS

CCDS43183.1

UniProtKB/Swiss-Prot

A8K474, B2RCR2, C9JEX1, P01042, P01043, Q53EQ0, Q6PAU9, Q7M4P1

UniProtKB/TrEMBL

B4E1C2

Related

ENSP00000493985.1, ENST00000644859.2

Conserved Domains (1) summary

cd00042
Location:266 → 370

CY; Cystatin-like domain; Cystatins are a family of cysteine protease inhibitors that occur mainly as single domain proteins. However some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains.
NM_001166451.2 → NP_001159923.1 kininogen-1 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice pattern in the 3' coding region and lacks an alternate in-frame exon, compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus and lacks an internal segment, compared to isoform 1.

Source sequence(s)

AC112907, CD014130

Consensus CDS

CCDS54695.1

UniProtKB/TrEMBL

B4DPP8, E9PEA0

Related

ENSP00000396025.1, ENST00000447445.1

Conserved Domains (1) summary

pfam00031
Location:230 → 324

Cystatin; Cystatin domain