congenital factor XI deficiency

Summary

congenital factor XI deficiency (MONDO:0012897) is a disease caused by F11 (GenCC Strong), with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe)
• Causal gene: F11 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 291
• Phenotypes (HPO): 9
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001892	Abnormal bleeding	Very frequent (80-99%)
HP:0001929	Reduced factor XI activity	Very frequent (80-99%)
HP:0003645	Prolonged partial thromboplastin time	Very frequent (80-99%)
HP:0006298	Prolonged bleeding after dental extraction	Very frequent (80-99%)
HP:0010989	Abnormality of the intrinsic pathway	Very frequent (80-99%)
HP:0000132	Menorrhagia	Frequent (30-79%)
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0002239	Gastrointestinal hemorrhage	Very rare (<1-4%)
HP:0005261	Joint hemorrhage	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital factor XI deficiency
Mondo ID	MONDO:0012897
OMIM	612416
Orphanet	329
DOID	DOID:2229
ICD-10-CM	D68.1
ICD-11	413739466
NCIT	C84705
SNOMED CT	49762007
UMLS	C0015523
MedGen	8770
GARD	0009670
Is cancer (heuristic)	no

Also known as: congenital factor XI deficiency · factor XI deficiency, autosomal dominant · factor XI deficiency, autosomal recessive · haemophilia C · hemophilia C · hereditary Factor XI deficiency · hereditary factor XI deficiency · hereditary factor XI deficiency disease · plasma thromboplastin antecedent deficiency · PTA deficiency · Rosenthal factor deficiency · Rosenthal syndrome · Rosenthal’s disease

Data availability: 291 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › congenital factor XI deficiency

Related subtypes (7): autosomal dominant disease, autosomal recessive disease, septooptic dysplasia, congenital factor XII deficiency, camptodactyly-tall stature-scoliosis-hearing loss syndrome, brachydactyly-syndactyly syndrome, Weill-Marchesani syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

291 retrieved; paginated sample, class counts are floors:

82 uncertain significance, 76 likely pathogenic, 40 conflicting classifications of pathogenicity, 32 pathogenic, 32 pathogenic/likely pathogenic, 17 benign, 7 benign/likely benign, 4 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
11891	NM_000128.4(F11):c.403G>T (p.Glu135Ter)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
11892	NM_000128.4(F11):c.901T>C (p.Phe301Leu)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
11893	NM_000128.4(F11):c.1029-2A>G	F11	Pathogenic	no assertion criteria provided
11894	NM_000128.4(F11):c.485+5G>C	F11	Pathogenic	no assertion criteria provided
11895	NM_000128.4(F11):c.1378T>G (p.Phe460Val)	F11	Pathogenic	no assertion criteria provided
11896	NM_000128.4(F11):c.438C>A (p.Cys146Ter)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11900	NM_000128.4(F11):c.1782C>A (p.Ser594Arg)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11901	NM_000128.4(F11):c.166T>C (p.Cys56Arg)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11903	NM_000128.4(F11):c.1253G>T (p.Gly418Val)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11904	NM_000128.4(F11):c.1760G>C (p.Trp587Ser)	F11	Pathogenic	no assertion criteria provided
11905	NC_000004.12:g.(186261554_186262508)_(?_186293752)del	F11	Pathogenic	no assertion criteria provided
1333004	Single allele	F11	Pathogenic	criteria provided, single submitter
1458941	NM_000128.4(F11):c.1026G>T (p.Gly342=)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1482231	NM_000128.4(F11):c.1060G>A (p.Gly354Arg)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188727	NM_000128.4(F11):c.1075del (p.Ile359fs)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188757	NM_000128.4(F11):c.961_962del (p.Cys321fs)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
188760	NM_000128.4(F11):c.1186C>T (p.Arg396Cys)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188795	NM_000128.4(F11):c.682C>T (p.Arg228Ter)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188810	NM_000128.4(F11):c.325G>A (p.Ala109Thr)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
188887	NM_000128.4(F11):c.1556G>A (p.Trp519Ter)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
188913	NM_000128.4(F11):c.400C>T (p.Gln134Ter)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188914	NM_000128.4(F11):c.408C>A (p.Cys136Ter)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
189094	NM_000128.4(F11):c.730C>T (p.Gln244Ter)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
189115	NM_000128.4(F11):c.1107C>A (p.Tyr369Ter)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
189122	NM_000128.4(F11):c.67C>T (p.Gln23Ter)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189129	NM_000128.4(F11):c.908del (p.Gly303fs)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
189138	NM_000128.4(F11):c.1313C>A (p.Ser438Ter)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2637829	NM_000128.4(F11):c.688T>A (p.Cys230Ser)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734695	NM_000128.4(F11):c.1103G>A (p.Gly368Glu)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
2768257	NM_000128.4(F11):c.1772G>A (p.Gly591Asp)	F11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
F11	Strong	Autosomal dominant	congenital factor XI deficiency	4
ZNF160	Strong	Autosomal dominant	congenital factor XI deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F11	Orphanet:329	Congenital factor XI deficiency
CYP4V2	Orphanet:41751	Bietti crystalline dystrophy

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZNF160	HGNC:12948	ENSG00000170949	Q9HCG1	Zinc finger protein 160	gencc,clinvar
F11	HGNC:3529	ENSG00000088926	P03951	Coagulation factor XI	gencc,clinvar
CYP4V2	HGNC:23198	ENSG00000145476	Q6ZWL3	Cytochrome P450 4V2	clinvar
F11-AS1	HGNC:27725	ENSG00000251165		F11 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZNF160	Zinc finger protein 160	May be involved in transcriptional regulation.
F11	Coagulation factor XI	Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
CYP4V2	Cytochrome P450 4V2	A cytochrome P450 monooxygenase involved in fatty acid metabolism in the eye.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	9.2×	0.419
Enzyme (other)	1	3.0×	0.538
Transcription factor	1	2.1×	0.538
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZNF160	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
F11	Protease	yes	3.4.21.27	Apple, Trypsin_dom, Peptidase_S1A
CYP4V2	Enzyme (other)	yes	1.14.14.79	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
F11-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	2
endothelial cell	1
pylorus	1
renal medulla	1
body of pancreas	1
right lobe of liver	1
ileal mucosa	1
kidney epithelium	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZNF160	294	ubiquitous	marker	renal medulla, endothelial cell, pylorus
F11	153	tissue_specific	marker	right lobe of liver, liver, body of pancreas
CYP4V2	254	ubiquitous	marker	kidney epithelium, ileal mucosa, liver
F11-AS1	150	tissue_specific	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP4V2	1,867
F11	1,005
ZNF160	517
F11-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F11	P03951	114

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CYP4V2	Q6ZWL3	91.05
ZNF160	Q9HCG1	68.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective F9 activation	1	634.4×	0.009	F11
FXIIa, PKa-dependent activation of coagulation pathway	1	380.7×	0.009	F11
Amplification and propagation of coagulation cascade	1	211.5×	0.010	F11
The canonical retinoid cycle in rods (twilight vision)	1	173.0×	0.010	CYP4V2
Endogenous sterols	1	131.3×	0.011	CYP4V2
Regulation of clotting cascade	1	77.7×	0.015	F11
Generic Transcription Pathway	1	5.0×	0.186	ZNF160

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of fibrinolysis	1	1123.5×	0.005	F11
fatty acid omega-oxidation	1	936.2×	0.005	CYP4V2
plasminogen activation	1	432.1×	0.007	F11
sterol metabolic process	1	280.9×	0.008	CYP4V2
retinoid metabolic process	1	165.2×	0.011	CYP4V2
hemopoiesis	1	89.2×	0.017	ZNF160
blood coagulation	1	57.9×	0.022	F11
visual perception	1	26.5×	0.042	CYP4V2
regulation of transcription by RNA polymerase II	1	3.9×	0.236	ZNF160

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 3

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
F11	MELAGATRAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F11	5	4
ZNF160	0	0
CYP4V2	0	0
F11-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MELAGATRAN	4	F11
MILVEXIAN	3	F11
FRUNEXIAN	2	F11
BMS-962212	1	F11
ONO-7684	1	F11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
F11	273	Binding:272, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F11	3.4.21.27	coagulation factor XIa
CYP4V2	1.14.14.79	docosahexaenoic acid omega-hydroxylase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
F11	273

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

5 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MELAGATRAN	4	F11
MILVEXIAN	3	F11
FRUNEXIAN	2	F11
BMS-962212	1	F11
ONO-7684	1	F11

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	F11
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CYP4V2
E	Difficult family or no structure, no drug	2	ZNF160, F11-AS1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ZNF160	0	—
CYP4V2	0	—
F11-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01538160	Not specified	UNKNOWN	A Single and Low Dose of Recombinant Factor VIIa in Patients With Severe Factor XI Deficiency Undergoing Surgery