KNG1 (kininogen 1)

Gene

• Entrez ID: 3827
• Gene name: Kininogen 1
• Gene symbol: KNG1
• Synonyms: BDK, BK, HAE6, HK, HMWK, KNG
• Chromosome: 3
• Chromosome location: 3q27.3
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918131	C>G,T	Pathogenic	Stop gained, missense variant, intron variant, coding sequence variant
rs797044429	A>-	Affects	Frameshift variant, intron variant, coding sequence variant
rs797044430	->C	Affects	Frameshift variant, intron variant, coding sequence variant
rs869320718	TTGTTGTTGTTGTTGTTTGTTTTTTGT>GGTGGTGGTGGTGGTGGTTTGTTTTTGG	Affects	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT021957	hsa-miR-128-3p	Microarray	17612493
MIRT755321	hsa-miR-942-5p	Luciferase reporter assay, Western blotting, Immunoprecipitaion (IP), Immunohistochemistry (IHC), qRT-PCR, Flow cytometry	36550594
MIRT1099502	hsa-miR-3689d	CLIP-seq
MIRT1099503	hsa-miR-4443	CLIP-seq
MIRT1099504	hsa-miR-496	CLIP-seq
MIRT2027022	hsa-miR-1253	CLIP-seq
MIRT2027023	hsa-miR-3174	CLIP-seq
MIRT2027024	hsa-miR-4499	CLIP-seq
MIRT2027025	hsa-miR-4762-3p	CLIP-seq
MIRT1099504	hsa-miR-496	CLIP-seq
MIRT2027026	hsa-miR-5096	CLIP-seq
MIRT2027027	hsa-miR-921	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002576	Process	Platelet degranulation	TAS
GO:0004866	Function	Endopeptidase inhibitor activity	IBA	21873635
GO:0004869	Function	Cysteine-type endopeptidase inhibitor activity	IBA	21873635
GO:0004869	Function	Cysteine-type endopeptidase inhibitor activity	IDA	3488317
GO:0005102	Function	Signaling receptor binding	IPI	11290596
GO:0005515	Function	Protein binding	IPI	8710908, 23082758
GO:0005576	Component	Extracellular region	HDA	27068509
GO:0005576	Component	Extracellular region	IBA	21873635
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	3488317
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0006954	Process	Inflammatory response	IEA
GO:0007162	Process	Negative regulation of cell adhesion	IDA	11970955
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IDA	16014619
GO:0007597	Process	Blood coagulation, intrinsic pathway	TAS
GO:0008201	Function	Heparin binding	NAS	12911595
GO:0008270	Function	Zinc ion binding	NAS	12911595
GO:0010951	Process	Negative regulation of endopeptidase activity	IBA	21873635
GO:0030195	Process	Negative regulation of blood coagulation	IBA	21873635
GO:0030195	Process	Negative regulation of blood coagulation	IDA	11970955
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0042311	Process	Vasodilation	IEA
GO:0043065	Process	Positive regulation of apoptotic process	NAS	12715893
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045861	Process	Negative regulation of proteolysis	IDA	3488317
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	25037231, 27559042, 28675934
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0072562	Component	Blood microparticle	HDA	22516433

Other IDs

• MIM: 612358
• HGNC: 6383
• e!Ensembl: ENSG00000113889

Protein

• UniProt ID: P01042
• Protein name: Kininogen-1 (Alpha-2-thiol proteinase inhibitor) (Fitzgerald factor) (High molecular weight kininogen) (HMWK) (Williams-Fitzgerald-Flaujeac factor) [Cleaved into: Kininogen-1 heavy chain; T-kinin (Ile-Ser-Bradykinin); Bradykinin (Kallidin I); Lysyl-bradyk
• Protein function: Kininogens are inhibitors of thiol proteases. HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; HMW-kininogen inhibits the thrombin- and plasmin-induced ag
• PDB: 1NY2, 2WOK, 4ASQ, 4ASR, 4ECB, 4ECC, 5I25, 6F27, 6F3V, 6F3W, 6F3X, 6F3Y, 7EIB, 7F2O, 7F6H, 7F6I, 7QOT, 7QOX, 8VJX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00031	Cystatin	21 → 116	Cystatin domain	Domain
  PF00031	Cystatin	144 → 238	Cystatin domain	Domain
  PF00031	Cystatin	266 → 360	Cystatin domain	Domain

• Sequence:

  MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYRIT
  EATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSSTKFS
  VATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHSSLFMLN
  EVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLR
  IASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLNAENNATFYFK
  IDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPW
  EKKIYPTVNCQPLGMISLMKRPPGFSPFRSSRIGEIKEETTVSPPHTSMAPAQDEERDSG
  KEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHGHEQQHGLGHGHKFKLD
  DDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTEHLASSSEDSTTPSAQTQE
  KTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAPIQSDDDWIPDIQIDPNGLSF
  NPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGLS

• Sequence length: 644

Pathways

KEGG:

cGMP-PKG signaling pathway
Sphingolipid signaling pathway
Neuroactive ligand-receptor interaction
Complement and coagulation cascades
Inflammatory mediator regulation of TRP channels
Regulation of actin cytoskeleton
Chagas disease
African trypanosomiasis
Pathways in cancer

Reactome:

Platelet degranulation
Intrinsic Pathway of Fibrin Clot Formation
Peptide ligand-binding receptors
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
G alpha (q) signalling events
G alpha (i) signalling events
Post-translational protein phosphorylation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Angioedema	Angioedemas, Hereditary, Acquired angioedema	rs28940870, rs1554996819, rs1554996817, rs112565881, rs2135304804, rs121907951, rs281875174, rs281875178, rs281875168, rs281875170, rs281875171, rs1554995255, rs1554995860, rs886041353, rs978962357, rs1554995774, rs763451792, rs1554995271, rs1554996833, rs1554995260, rs1565169419, rs1565173405, rs1565168898, rs1590822296, rs1565169621, rs1565170287, rs1565170364, rs1565171906, rs1565173309, rs1565174105, rs922149386, rs1590822719, rs1590821401, rs1590822588, rs1590822739, rs1590823884, rs1590826571, rs1590829609, rs1590829616, rs1590829763, rs1590831385, rs1590831432, rs956390201, rs1590831545, rs1590829685, rs778625408, rs1582955358, rs1599142041, rs1945310324, rs1945307391, rs1945416520	9734886
Dermatitis	Dermatitis, Occupational	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	30685357
High molecular weight kininogen deficiency	High molecular weight kininogen deficiency	rs121918131, rs797044429, rs869320718, rs797044430	28053049, 7901207, 17522339
Hypertension	Hypertensive disease	rs13306026, rs13333226	7027322
Total kininogen deficiency	Kininogen Deficiency, Total	rs121918131

Unknown
Disease name	Disease term	dbSNP ID	References
Congenital high-molecular-weight kininogen deficiency	Congenital high-molecular-weight kininogen deficiency
Hyperemia	Hyperemia		11837250
Industrial dermatosis	Industrial Dermatosis		30685357
Kidney failure	Kidney Failure, Acute		3015452, 513486
Acute kidney insufficiency	Acute Kidney Insufficiency		3015452, 513486