F12 coagulation factor XII [Homo sapiens (human)] - Gene

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; AllianceGenome:HGNC:3530
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: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 5q35.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (177402141..177409564, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (177945359..177952782, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (176829142..176836565, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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 Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Factor XII Deficiency in Mexico: High Prevalence in the General Population and Patients with Venous Thromboembolic Disease.
Title: Factor XII Deficiency in Mexico: High Prevalence in the General Population and Patients with Venous Thromboembolic Disease.
[Genetic analysis of a Chinese pedigree affected with Congenital coagulation factor XII deficiency due to a c.1A>G start codon variant of F12 gene].
Title: [Genetic analysis of a Chinese pedigree affected with Congenital coagulation factor XII deficiency due to a c.1A>G start codon variant of F12 gene].
[Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor deficiency].
Title: [Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor Ⅻ deficiency].
Characterization of congenital factor XII deficiency in Taiwanese patients: identification of one novel and one common mutation.
Title: Characterization of congenital factor XII deficiency in Taiwanese patients: identification of one novel and one common mutation.
Factor XII in PMM2-CDG patients: role of N-glycosylation in the secretion and function of the first element of the contact pathway.
Title: Factor XII in PMM2-CDG patients: role of N-glycosylation in the secretion and function of the first element of the contact pathway.
Contact activation-induced complex formation between complement factor H and coagulation factor XIIa.
Title: Contact activation-induced complex formation between complement factor H and coagulation factor XIIa.
Factor XII Concentrations and Risk of Intracerebral Haemorrhage. A Prospective Case-Referent Study.
Title: Factor XII Concentrations and Risk of Intracerebral Haemorrhage. A Prospective Case-Referent Study.
A mutation in the kringle domain of human factor XII that causes autoinflammation, disturbs zymogen quiescence, and accelerates activation.
Title: A mutation in the kringle domain of human factor XII that causes autoinflammation, disturbs zymogen quiescence, and accelerates activation.
The functional promoter F12-46C/T variant predicts the asymptomatic phenotype of C1-INH-HAE.
Title: The functional promoter F12-46C/T variant predicts the asymptomatic phenotype of C1-INH-HAE.
he 46TT genetype, p.Glu502Lys and p.Gly542Ser variants of the F12 gene probably underlie the low FXII level in the proband with hereditary coagulation factor XII (FXII) deficiency
Title: [Identification of compound heterozygous variants of F12 gene in a pedigree affected with inherited coagulation factor XII deficiency].

Submit: New GeneRIF Correction See all GeneRIFs (152)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Factor XII deficiency disease MedGen: C0015526 OMIM: 234000 GeneReviews: Not available	Compare labs
Hereditary angioedema type 3 MedGen: C1857728 OMIM: 610618 GeneReviews: Not available	Compare labs

EBI 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. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1. EBI GWAS Catalog EBI GWAS CatalogPubMed
New loci associated with kidney function and chronic kidney disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH67849 (e-PCR)
- UniSTS:67854

RH47779 (e-PCR)
- UniSTS:4386

RH70295 (e-PCR)
- UniSTS:45138

STS-W95094 (e-PCR)
- UniSTS:77426

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables misfolded protein binding	IC Inferred by Curator more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Factor XII activation	IDA Inferred from Direct Assay more info	PubMed
involved_in blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in blood coagulation, intrinsic pathway	IC Inferred by Curator more info	PubMed
involved_in fibrinolysis	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in plasma kallikrein-kinin cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of blood coagulation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of plasminogen activation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoprocessing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in response to misfolded protein	IDA Inferred from Direct Assay more info	PubMed
involved_in zymogen activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in zymogen activation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in rough endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info

General protein information

Go to the top of the page Help

Preferred Names: coagulation factor XII

Names: Hageman factor; Plasma coagulation Factor XIIa; beta-factor XIIa part 1; beta-factor XIIa part 2; coagulation factor XIIa heavy chain; coagulation factor XIIa light chain

NP_000496.2

EC 3.4.21.38

XP_011532764.1

EC 3.4.21.38

XP_054208022.1

EC 3.4.21.38

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_007568.1 RefSeqGene

Range

5001..12439

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_145

mRNA and Protein(s)

NM_000505.4 → NP_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, P78339

UniProtKB/TrEMBL

A0AA51Z0K1

Related

ENSP00000253496.3, ENST00000253496.4

Conserved Domains (7) summary

smart00059
Location:41 → 88

FN2; Fibronectin type 2 domain

smart00020
Location:372 → 609

Tryp_SPc; Trypsin-like serine protease

cd00054
Location:96 → 131

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:133 → 173

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:373 → 612

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:178 → 206

EGF; EGF-like domain

pfam00051
Location:217 → 295

Kringle; Kringle domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

177402141..177409564 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011534462.3 → XP_011532764.1 coagulation factor XII isoform X1

UniProtKB/TrEMBL

A0AA51Z0K1

Conserved Domains (5) summary

smart00020
Location:260 → 497

Tryp_SPc; Trypsin-like serine protease

cd00061
Location:21 → 61

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:261 → 500

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:66 → 94

EGF; EGF-like domain

pfam00051
Location:105 → 183

Kringle; Kringle domain