GeneBe

F12

coagulation factor XII

Basic information

Region (hg38): 5:177402133-177416583

Links

ENSG00000131187 ∙ NCBI:2161 ∙ OMIM:610619 ∙ HGNC:3530 ∙ Uniprot:P00748 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hereditary angioedema type 3 (Strong), mode of inheritance: AD
  • congenital factor XII deficiency (Supportive), mode of inheritance: AR
  • hereditary angioedema type 3 (Supportive), mode of inheritance: AD
  • hereditary angioedema type 3 (Strong), mode of inheritance: AD
  • congenital factor XII deficiency (Strong), mode of inheritance: AR
  • hereditary angioedema type 3 (Definitive), mode of inheritance: AD
  • congenital factor XII deficiency (Definitive), mode of inheritance: AR
  • hereditary angioedema type 3 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Angioedema, hereditary, 3AD/ARAllergy/Immunology/Infectious; PharmacogenomicIn Hereditary angioedema, attacks, which can include potentially life-threatening upper airway obstruction, can be precipitated by high estrogen levels (eg, pregnancy, OCPs)Allergy/Immunology/Infectious; Hematologic14490552; 4968868; 5432188; 6348471; 2882793; 2110579; 1905067; 8419231; 7947293; 11069485; 15306750; 15013868; 15678272; 19477491; 20729721; 20667118; 20695852; 21849258; 20729721; 21297451; 22043782; 22801442; 22197449; 22729959

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the F12 gene.

  • not_provided (98 variants)
  • Inborn_genetic_diseases (65 variants)
  • Factor_XII_deficiency_disease (47 variants)
  • Hereditary_angioedema_type_3 (42 variants)
  • F12-related_disorder (21 variants)
  • Hereditary_angioneurotic_edema (5 variants)
  • Nephrolithiasis/osteoporosis,_hypophosphatemic (4 variants)
  • not_specified (3 variants)
  • Hypertensive_disorder (1 variants)
  • Urticaria (1 variants)
  • Thrombus (1 variants)
  • Angioedema (1 variants)
  • FACTOR_XII_(WASHINGTON_D.C.) (1 variants)
  • FACTOR_XII_(LOCARNO) (1 variants)
  • Hyperbilirubinemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the F12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000505.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
31
clinvar
1
clinvar
 39
missense
4
clinvar
1
clinvar
84
clinvar
16
clinvar
2
clinvar
 107
nonsense
4
clinvar
 4
start loss
0
frameshift
2
clinvar
1
clinvar
2
clinvar
 5
splice donor/acceptor (+/-2bp)
1
clinvar
5
clinvar
 6
Total 7 11 93 47 3

Highest pathogenic variant AF is 0.000340259

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
F12protein_codingprotein_codingENST00000253496 147437
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
8.25e-80.99612559901471257460.000585
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9243073560.8620.00001853891
Missense in Polyphen114138.090.825561607
Synonymous0.4811471550.9510.000008031229
Loss of Function2.571732.90.5170.00000153355

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004350.000427
Ashkenazi Jewish0.004460.00428
East Asian0.0006700.000653
Finnish0.0001460.0000924
European (Non-Finnish)0.0005910.000536
Middle Eastern0.0006700.000653
South Asian0.0005070.000490
Other0.0005030.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta- factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. {ECO:0000269|PubMed:21304106}.;
Disease
DISEASE: Factor XII deficiency (FA12D) [MIM:234000]: An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)- negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). {ECO:0000269|PubMed:10361128, ECO:0000269|PubMed:11776307, ECO:0000269|PubMed:15205584, ECO:0000269|PubMed:15617741, ECO:0000269|PubMed:2510163, ECO:0000269|PubMed:2882793, ECO:0000269|PubMed:8049433, ECO:0000269|PubMed:8528215, ECO:0000269|PubMed:9354665}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hereditary angioedema 3 (HAE3) [MIM:610618]: An hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). {ECO:0000269|PubMed:16638441, ECO:0000269|PubMed:17186468}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Complement and coagulation cascades - Homo sapiens (human);Aminocaproic Acid Action Pathway;Tranexamic Acid Action Pathway;Urokinase Action Pathway;Reteplase Action Pathway;Streptokinase Action Pathway;Tenecteplase Action Pathway;Alteplase Action Pathway;Anistreplase Action Pathway;Aprotinin Action Pathway;Phenindione Action Pathway;Dicoumarol Action Pathway;Warfarin Action Pathway;Acenocoumarol Action Pathway;Coagulation ;Bivalirudin Action Pathway;Argatroban Action Pathway;Ardeparin Action Pathway;Heparin Action Pathway;Fondaparinux Action Pathway;Enoxaparin Action Pathway;Phenprocoumon Action Pathway;Dicumarol Action Pathway;Ximelagatran Action Pathway;Lepirudin Action Pathway;Blood Clotting Cascade;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Complement and Coagulation Cascades;intrinsic prothrombin activation pathway;Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade) (Consensus)

Recessive Scores

pRec
0.0955

Intolerance Scores

loftool
0.323
rvis_EVS
0.53
rvis_percentile_EVS
80.96

Haploinsufficiency Scores

pHI
0.287
hipred
N
hipred_score
0.274
ghis
0.446

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.528

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
F12
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process
plasma kallikrein-kinin cascade;Factor XII activation;proteolysis;blood coagulation, intrinsic pathway;positive regulation of plasminogen activation;protein processing;protein autoprocessing;positive regulation of blood coagulation;zymogen activation;fibrinolysis;innate immune response;response to misfolded protein;positive regulation of fibrinolysis
Cellular component
extracellular region;extracellular space;rough endoplasmic reticulum;plasma membrane;extracellular exosome
Molecular function
serine-type endopeptidase activity;calcium ion binding;protein binding;misfolded protein binding