congenital factor X deficiency

Summary

congenital factor X deficiency (MONDO:0009212) is a disease caused by F10 (GenCC Definitive), with 4 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: F10 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 74
• Phenotypes (HPO): 19

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0008151	Prolonged prothrombin time	Obligate (100%)
HP:0008321	Reduced factor X activity	Obligate (100%)
HP:0004846	Prolonged bleeding after surgery	Very frequent (80-99%)
HP:0006298	Prolonged bleeding after dental extraction	Very frequent (80-99%)
HP:0000225	Gingival bleeding	Frequent (30-79%)
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0000132	Menorrhagia	Occasional (5-29%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0000978	Bruising susceptibility	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)
HP:0005261	Joint hemorrhage	Occasional (5-29%)
HP:0007420	Spontaneous hematomas	Occasional (5-29%)
HP:0011884	Abnormal umbilical stump bleeding	Occasional (5-29%)
HP:0011891	Post-partum hemorrhage	Occasional (5-29%)
HP:0012233	Intramuscular hematoma	Occasional (5-29%)
HP:0025328	Antepartum hemorrhage	Occasional (5-29%)
HP:0030140	Oral cavity bleeding	Occasional (5-29%)
HP:0002138	Subarachnoid hemorrhage	Very rare (<1-4%)
HP:0011854	Hemoperitoneum	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital factor X deficiency
Mondo ID	MONDO:0009212
OMIM	227600
Orphanet	328
DOID	DOID:2222
ICD-11	1886781445
NCIT	C98940
SNOMED CT	37350004
UMLS	C0272327
MedGen	543976
GARD	0006404
Is cancer (heuristic)	no

Also known as: congenital factor X deficiency · congenital Stuart factor deficiency · factor X deficiency, congenital · hereditary Factor X deficiency · Stuart factor deficiency, congenital · Stuart-Prower factor deficiency

Data availability: 74 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › factor X deficiency › congenital factor X deficiency

Related subtypes (1): acquired factor X deficiency

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

74 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 22 likely pathogenic, 9 conflicting classifications of pathogenicity, 7 benign, 4 pathogenic, 3 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1341356	NM_000504.4(F10):c.1216G>A (p.Gly406Ser)	F10	Pathogenic	criteria provided, single submitter
1684308	NM_000504.4(F10):c.162_163del (p.Glu56fs)	F10	Pathogenic	no assertion criteria provided
1684490	NM_000504.4(F10):c.837C>A (p.Tyr279Ter)	F10	Pathogenic	no assertion criteria provided
4845820	NM_000504.4(F10):c.71-1G>C	F10	Pathogenic	criteria provided, single submitter
1679953	NM_000504.4(F10):c.1073C>T (p.Thr358Met)	F10	Likely pathogenic	criteria provided, single submitter
1684307	NM_000504.4(F10):c.205G>A (p.Glu69Lys)	F10	Likely pathogenic	no assertion criteria provided
1684309	NM_000504.4(F10):c.1252G>C (p.Asp418His)	F10	Likely pathogenic	criteria provided, single submitter
1703258	NM_000504.4(F10):c.232-2563_503-451del	F10	Likely pathogenic	criteria provided, single submitter
2505497	NM_000504.4(F10):c.270T>A (p.Cys90Ter)	F10	Likely pathogenic	criteria provided, single submitter
2505498	NM_000504.4(F10):c.256G>A (p.Asp86Asn)	F10	Likely pathogenic	criteria provided, single submitter
2505499	NM_000504.4(F10):c.167A>G (p.Glu56Gly)	F10	Likely pathogenic	criteria provided, single submitter
2505500	NM_000504.4(F10):c.248_251del (p.Lys83fs)	F10	Likely pathogenic	criteria provided, single submitter
2505501	NM_000504.4(F10):c.299_300del (p.Lys100fs)	F10	Likely pathogenic	criteria provided, single submitter
2505502	NM_000504.4(F10):c.305_306del (p.Lys102fs)	F10	Likely pathogenic	criteria provided, single submitter
2572121	NM_000504.4(F10):c.119G>C (p.Arg40Thr)	F10	Likely pathogenic	criteria provided, single submitter
2572129	NM_000504.4(F10):c.1036C>T (p.Arg346Cys)	F10	Likely pathogenic	criteria provided, single submitter
2572143	NM_000504.4(F10):c.212T>C (p.Phe71Ser)	F10	Likely pathogenic	criteria provided, single submitter
3065348	NM_000504.4(F10):c.815T>C (p.Leu272Pro)	F10	Likely pathogenic	criteria provided, single submitter
3575773	NM_000504.4(F10):c.183_184delinsTTGCTCATACGAAGAGGCCC (p.Arg68_Glu69insSerTyrGluGluAlaArg)	F10	Likely pathogenic	criteria provided, single submitter
3575774	NM_000504.4(F10):c.1331C>T (p.Ala444Val)	F10	Likely pathogenic	criteria provided, single submitter
4277962	NM_000504.4(F10):c.1147C>G (p.Pro383Ala)	F10	Likely pathogenic	criteria provided, single submitter
626923	NM_000504.4(F10):c.1210T>C (p.Cys404Arg)	F10	Likely pathogenic	criteria provided, single submitter
626926	NM_000504.4(F10):c.1348G>A (p.Gly450Arg)	F10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
626966	NM_000504.4(F10):c.1087G>A (p.Gly363Ser)	F10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
627253	NM_000504.4(F10):c.161A>G (p.Glu54Gly)	F10-AS1	Likely pathogenic	criteria provided, single submitter
627505	Single allele	F11	Likely pathogenic	criteria provided, single submitter
12061	NM_000504.4(F10):c.424G>A (p.Glu142Lys)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676734	NM_000504.4(F10):c.947A>G (p.Lys316Arg)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676735	NM_000504.4(F10):c.1351A>C (p.Ile451Leu)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
311268	NM_000504.4(F10):c.57G>A (p.Leu19=)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
F10	Definitive	Autosomal recessive	congenital factor X deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F10	Orphanet:328	Congenital factor X deficiency
F11	Orphanet:329	Congenital factor XI deficiency

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
F10	HGNC:3528	ENSG00000126218	P00742	Coagulation factor X	gencc,clinvar
ZNF160	HGNC:12948	ENSG00000170949	Q9HCG1	Zinc finger protein 160	clinvar
F11	HGNC:3529	ENSG00000088926	P03951	Coagulation factor XI	clinvar
F10-AS1	HGNC:40225	ENSG00000231882		F10 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F10	Coagulation factor X	Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
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.

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	2	18.3×	0.013
Transcription factor	1	2.1×	0.605
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F10	Protease	yes	3.4.21.6	EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF
ZNF160	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
F11	Protease	yes	3.4.21.27	Apple, Trypsin_dom, Peptidase_S1A
F10-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 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
right lobe of liver	2
stromal cell of endometrium	1
endothelial cell	1
pylorus	1
renal medulla	1
body of pancreas	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F10	176	broad	marker	right lobe of liver, liver, stromal cell of endometrium
ZNF160	294	ubiquitous	marker	renal medulla, endothelial cell, pylorus
F11	153	tissue_specific	marker	right lobe of liver, liver, body of pancreas
F10-AS1	122		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
F10	1,326
F11	1,005
ZNF160	517
F10-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F10	P00742	188
F11	P03951	114

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF160	Q9HCG1	68.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Amplification and propagation of coagulation cascade	2	423.0×	8e-05	F10, F11
Regulation of clotting cascade	2	155.4×	3e-04	F10, F11
Defective factor IX causes thrombophilia	1	1268.9×	0.002	F10
Defective cofactor function of FVIIIa variant	1	1268.9×	0.002	F10
Defective F9 variant does not activate FX	1	1268.9×	0.002	F10
Defective F9 activation	1	634.4×	0.003	F11
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	423.0×	0.003	F10
Gamma-carboxylation of protein precursors	1	380.7×	0.003	F10
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	380.7×	0.003	F10
FXIIa, PKa-dependent activation of coagulation pathway	1	380.7×	0.003	F11
Initiation of coagulation cascade	1	158.6×	0.007	F10
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
blood coagulation	2	115.8×	8e-04	F10, F11
positive regulation of fibrinolysis	1	1123.5×	0.004	F11
plasminogen activation	1	432.1×	0.006	F11
positive regulation of TOR signaling	1	165.2×	0.012	F10
hemopoiesis	1	89.2×	0.018	ZNF160
positive regulation of cell migration	1	20.6×	0.064	F10
proteolysis	1	11.4×	0.097	F10
regulation of transcription by RNA polymerase II	1	3.9×	0.236	ZNF160

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
F10	ARGATROBAN
F11	MELAGATRAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F10	23	4
F11	5	4
ZNF160	0	0
F10-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ARGATROBAN	4	F10
FONDAPARINUX SODIUM	4	F10
FONDAPARINUX	4	F10
EDOXABAN	4	F10
RIVAROXABAN	4	F10
APIXABAN	4	F10
MELAGATRAN	4	F10, F11
BETRIXABAN	4	F10
PENTAMIDINE	4	F10
DAREXABAN	3	F10
NAFAMOSTAT	3	F10
OTAMIXABAN	3	F10
DABIGATRAN	3	F10
GABEXATE	3	F10
MILVEXIAN	3	F11
LETAXABAN	2	F10
TANOGITRAN	2	F10
LY-517717	2	F10
RAZAXABAN	2	F10
GW813893	2	F10
EFEGATRAN	2	F10
SEGATROXABAN	2	F10
ERIBAXABAN	2	F10
FIDEXABAN	2	F10
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
F10	795	Binding:779, Functional:9, ADMET:7
F11	273	Binding:272, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F10	3.4.21.6	coagulation factor Xa
F11	3.4.21.27	coagulation factor XIa

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
F10	795
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

27 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)
ARGATROBAN	4	F10
FONDAPARINUX SODIUM	4	F10
FONDAPARINUX	4	F10
EDOXABAN	4	F10
RIVAROXABAN	4	F10
APIXABAN	4	F10
MELAGATRAN	4	F10, F11
BETRIXABAN	4	F10
PENTAMIDINE	4	F10
DAREXABAN	3	F10
NAFAMOSTAT	3	F10
OTAMIXABAN	3	F10
DABIGATRAN	3	F10
GABEXATE	3	F10
MILVEXIAN	3	F11
LETAXABAN	2	F10
TANOGITRAN	2	F10
LY-517717	2	F10
RAZAXABAN	2	F10
GW813893	2	F10
EFEGATRAN	2	F10
SEGATROXABAN	2	F10
ERIBAXABAN	2	F10
FIDEXABAN	2	F10
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)	2	F10, F11
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ZNF160, F10-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZNF160	0	—
F10-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.