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    F12 coagulation factor XII [ Homo sapiens (human) ]

    Gene ID: 2161, updated on 16-Sep-2018

    Summary

    Official Symbol
    F12provided by HGNC
    Official Full Name
    coagulation factor XIIprovided by HGNC
    Primary source
    HGNC:HGNC:3530
    See related
    Ensembl:ENSG00000131187 MIM:610619; Vega:OTTHUMG00000163403
    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
    HAF; HAE3; HAEX
    Summary
    This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy chain contains two fibronectin-type domains, two epidermal growth factor (EGF)-like domains, a kringle domain and a proline-rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta-factor XIIa light chain and the alpha-factor XIIa light chain becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then to beta-factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause any clinical symptoms and the sole effect is that whole-blood clotting time is prolonged. [provided by RefSeq, Jul 2008]
    Expression
    Restricted expression toward liver (RPKM 77.8) See more
    Orthologs

    Genomic context

    See F12 in Genome Data Viewer
    Location:
    5q35.3
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (177402138..177409576, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (176829139..176836577, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene VISTA enhancer hs2229 Neighboring gene solute carrier family 34 member 1 Neighboring gene profilin 3 Neighboring gene G protein-coupled receptor kinase 6 Neighboring gene PRR7 antisense RNA 1 Neighboring gene proline rich 7, synaptic Neighboring gene drebrin 1

    Genomic regions, transcripts, and products

    Expression

    • Project title: 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 Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Factor XII deficiency disease
    MedGen: C0015526 OMIM: 234000 GeneReviews: Not available
    Compare labs
    Hereditary angioneurotic edema with normal C1 esterase inhibitor activity
    MedGen: C1857728 OMIM: 610618 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1.
    NHGRI GWA Catalog
    An atlas of genetic influences on human blood metabolites.
    NHGRI GWA Catalog
    Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time.
    NHGRI GWA Catalog
    Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.
    NHGRI GWA Catalog
    Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
    NHGRI GWA Catalog
    Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1.
    NHGRI GWA Catalog
    New loci associated with kidney function and chronic kidney disease.
    NHGRI GWA Catalog
    Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
    NHGRI GWA Catalog
    Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children.
    NHGRI GWA Catalog

    Pathways from BioSystems

    • Blood Clotting Cascade, organism-specific biosystem (from WikiPathways)
      Blood Clotting Cascade, organism-specific biosystemCoagulation is a complex process by which blood forms clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel), wherein a damaged blood vessel wall is covered ...
    • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
      Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
    • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
      Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Complement and coagulation cascades, conserved biosystem (from KEGG)
      Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
      Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
      Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystemThe intrinsic pathway of blood clotting connects interactions among kininogen (high molecular weight kininogen, HK), prekallikrein (PK), and factor XII to the activation of clotting factor X by a ser...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    misfolded protein binding IC
    Inferred by Curator
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    serine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    Factor XII activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    blood coagulation, intrinsic pathway IC
    Inferred by Curator
    more info
    PubMed 
    blood coagulation, intrinsic pathway TAS
    Traceable Author Statement
    more info
     
    fibrinolysis IEA
    Inferred from Electronic Annotation
    more info
     
    innate immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    plasma kallikrein-kinin cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of blood coagulation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of fibrinolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of plasminogen activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein autoprocessing IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein processing IDA
    Inferred from Direct Assay
    more info
    PubMed 
    proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    response to misfolded protein IDA
    Inferred from Direct Assay
    more info
    PubMed 
    zymogen activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    extracellular exosome HDA PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    rough endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 

    General protein information

    Preferred Names
    coagulation factor XII
    Names
    Hageman factor
    beta-factor XIIa part 1
    beta-factor XIIa part 2
    coagulation factor XIIa heavy chain
    coagulation factor XIIa light chain
    NP_000496.2
    XP_011532764.1

    NCBI Reference Sequences (RefSeq)

    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

    1. NG_007568.1 RefSeqGene

      Range
      5001..12439
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_145

    mRNA and Protein(s)

    1. NM_000505.3NP_000496.2  coagulation factor XII preproprotein

      See identical proteins and their annotated locations for NP_000496.2

      Status: REVIEWED

      Source sequence(s)
      AB095845, AC145098, BE139501, M11723
      Consensus CDS
      CCDS34302.1
      UniProtKB/Swiss-Prot
      P00748
      UniProtKB/TrEMBL
      Q8IZZ5
      Related
      ENSP00000253496.3, OTTHUMP00000223845, ENST00000253496.3, OTTHUMT00000373217
      Conserved Domains (7) summary
      smart00059
      Location:4188
      FN2; Fibronectin type 2 domain
      smart00020
      Location:372609
      Tryp_SPc; Trypsin-like serine protease
      cd00054
      Location:96131
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      cd00061
      Location:133173
      FN1; Fibronectin type 1 domain, approximately 40 residue long with two conserved disulfide bridges. FN1 is one of three types of internal repeats which combine to form larger domains within fibronectin. Fibronectin, a plasma protein that binds cell surfaces ...
      cd00190
      Location:373612
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      pfam00008
      Location:178206
      EGF; EGF-like domain
      pfam00051
      Location:217295
      Kringle; Kringle domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

      Range
      177402138..177409576 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011534462.2XP_011532764.1  coagulation factor XII isoform X1

      Conserved Domains (5) summary
      smart00020
      Location:260497
      Tryp_SPc; Trypsin-like serine protease
      cd00061
      Location:2161
      FN1; Fibronectin type 1 domain, approximately 40 residue long with two conserved disulfide bridges. FN1 is one of three types of internal repeats which combine to form larger domains within fibronectin. Fibronectin, a plasma protein that binds cell surfaces ...
      cd00190
      Location:261500
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      pfam00008
      Location:6694
      EGF; EGF-like domain
      pfam00051
      Location:105183
      Kringle; Kringle domain
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