F11

coagulation factor XI

Basic information

Region (hg38): 4:186266189-186289681

Links

ENSG00000088926 ∙ NCBI:2160 ∙ OMIM:264900 ∙ HGNC:3529 ∙ Uniprot:P03951 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital factor XI deficiency (Supportive), mode of inheritance: AD
• congenital factor XI deficiency (Definitive), mode of inheritance: Semidominant
• congenital factor XI deficiency (Strong), mode of inheritance: AD
• congenital factor XI deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Factor XI deficiency	AD/AR	Hematologic; Pharmacogenomic	Individuals may be at risk of bleeding (eg, following surgery or with injury, and during delivery), and prophylaxis and preventive measures (eg, including avoidance of aspirin) and prompt treatment (eg, with fresh frozen plasma) may be beneficial, including considerations prior to/during pregnancy; Antifibrinolytic therapy may be beneficial in females with menorrhagia	Hematologic	3871646; 2439152; 3553944; 2813350; 8800510; 18434707; 18160615; 19598070; 19367158; 19049995; 21577094; 21699628; 22624777; 22726099
Heterozygotes may have manifestations that warrant interventions

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the F11 gene.

• not provided (41 variants)
• Hereditary factor XI deficiency disease (11 variants)
• Plasma factor XI deficiency (6 variants)
• F11-related disorder (4 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• Factor XI (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the F11 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	125	7	133
missense	8	34	73	6	1	122
nonsense	12	24	1			37
start loss	1	2				3
frameshift	17	28	1			46
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	4	25				29
splice region	1	2	4	30	1	38
non coding			27	66	44	137
Total	42	114	104	197	52

Highest pathogenic variant AF is 0.000657

Variants in F11

This is a list of pathogenic ClinVar variants found in the F11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-186266227-G-A		Hereditary factor XI deficiency disease	Uncertain significance (Jan 13, 2018)
4-186266240-G-A		Hereditary factor XI deficiency disease • Plasma factor XI deficiency	Uncertain significance (Jan 13, 2018)
4-186266243-G-A		Hereditary factor XI deficiency disease • Plasma factor XI deficiency	Benign/Likely benign (Jan 29, 2024)
4-186266295-G-C		Hereditary factor XI deficiency disease	Uncertain significance (Feb 01, 2019)
4-186266907-T-C			Benign (Nov 11, 2018)
4-186266940-T-G			Benign (May 11, 2021)
4-186266987-G-GAT			Benign (May 13, 2021)
4-186266998-A-C		Hereditary factor XI deficiency disease	Benign (Jul 10, 2021)
4-186267129-ATTGTAGGATGATTTTC-A			Pathogenic (Jun 24, 2023)
4-186267138-T-A		Hereditary factor XI deficiency disease	Likely pathogenic (Jul 13, 2017)
4-186267139-G-T		Hereditary factor XI deficiency disease	Likely pathogenic (Apr 09, 2022)
4-186267142-T-A			Likely benign (Apr 27, 2023)
4-186267152-C-T		Hereditary factor XI deficiency disease	Pathogenic/Likely pathogenic (Feb 04, 2023)
4-186267153-A-G			Uncertain significance (May 11, 2023)
4-186267160-ACATT-A		Hereditary factor XI deficiency disease	Likely pathogenic (Mar 03, 2016)
4-186267162-A-G		F11-related disorder	Uncertain significance (Feb 15, 2024)
4-186267172-ATT-A		Hereditary factor XI deficiency disease	Likely pathogenic (Mar 30, 2022)
4-186267181-A-C			Likely benign (Apr 01, 2024)
4-186267186-C-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
4-186267190-TG-T			Pathogenic (Dec 23, 2021)
4-186267193-T-C			Likely pathogenic (May 18, 2021)
4-186267197-T-G		Hereditary factor XI deficiency disease	Uncertain significance (-)
4-186267197-T-GAG		Hereditary factor XI deficiency disease	Uncertain significance (Feb 16, 2017)
4-186267207-T-G			Likely benign (Nov 20, 2023)
4-186271327-T-C			Benign (Nov 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
F11	protein_coding	protein_coding	ENST00000403665	14	23737

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.61e-26	0.0000690	125376	3	369	125748	0.00148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0199	342	343	0.997	0.0000195	4099
Missense in Polyphen		136	137.48	0.98922		1684
Synonymous	-0.487	137	130	1.05	0.00000861	1166
Loss of Function	-0.530	37	33.7	1.10	0.00000172	414

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000807	0.000807
Ashkenazi Jewish	0.0171	0.0169
East Asian	0.00326	0.00327
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000713	0.000712
Middle Eastern	0.00326	0.00327
South Asian	0.000882	0.000882
Other	0.00212	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
• Disease: DISEASE: Factor XI deficiency (FA11D) [MIM:612416]: A hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate. {ECO:0000269|PubMed:10027710, ECO:0000269|PubMed:10606881, ECO:0000269|PubMed:11895778, ECO:0000269|PubMed:15026311, ECO:0000269|PubMed:15180874, ECO:0000269|PubMed:1547342, ECO:0000269|PubMed:15953011, ECO:0000269|PubMed:16607084, ECO:0000269|PubMed:18005151, ECO:0000269|PubMed:21457405, ECO:0000269|PubMed:21668437, ECO:0000269|PubMed:21999818, ECO:0000269|PubMed:22016685, ECO:0000269|PubMed:22159456, ECO:0000269|PubMed:22322133, ECO:0000269|PubMed:25158988, ECO:0000269|PubMed:2813350, ECO:0000269|PubMed:7669672, ECO:0000269|PubMed:7888672, ECO:0000269|PubMed:9401068, ECO:0000269|PubMed:9787168}. 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 Blood Clotting Cascade;intrinsic prothrombin activation pathway;Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade) (Consensus)

Recessive Scores

• pRec: 0.483

Intolerance Scores

• loftool: 0.207
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.68

Haploinsufficiency Scores

• pHI: 0.0456
• hipred: N
• hipred_score: 0.313
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.780

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: F11
• Phenotype: immune system 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: blood coagulation;blood coagulation, intrinsic pathway;plasminogen activation;positive regulation of fibrinolysis
• Cellular component: extracellular region;extracellular space;plasma membrane;membrane;extracellular exosome
• Molecular function: serine-type endopeptidase activity;protein binding;heparin binding;serine-type aminopeptidase activity