hemophilia B leyden

Summary

hemophilia B leyden (MONDO:0850054) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemophilia B leyden
Mondo ID	MONDO:0850054
Orphanet	617930
UMLS	C5848256
MedGen	1845499
GARD	0022455
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › hemophilia B leyden

Related subtypes (27): inherited bleeding disorder, platelet-type, factor VII deficiency, factor X deficiency, purpura, vascular hemostatic disease, congenital factor V deficiency, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, hemophilia A, hemophilia B, East Texas bleeding disorder, congenital factor XI deficiency, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital factor XIII deficiency, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, acquired hemophilia, fetal and neonatal alloimmune thrombocytopenia, hereditary von Willebrand disease, acquired von willebrand syndrome, prothrombin 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

6 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10558	NC_000023.11:g.139530716T>A	F9	Pathogenic	no assertion criteria provided
10561	NM_000133.4(F9):c.-17del	F9	Pathogenic	no assertion criteria provided
10644	NM_000133.4(F9):c.-22T>C	F9	Pathogenic	no assertion criteria provided
10645	NC_000023.11:g.139530731A>T	F9	Pathogenic	no assertion criteria provided
10646	NM_000133.4(F9):c.-17A>G	F9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
641767	NM_000133.4(F9):c.-35G>A	F9	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F9	Orphanet:169793	Severe hemophilia B
F9	Orphanet:169796	Moderate hemophilia B
F9	Orphanet:169799	Mild hemophilia B
F9	Orphanet:177929	Bleeding disorder in hemophilia B carriers

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
F9	HGNC:3551	ENSG00000101981	P00740	Coagulation factor IX	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F9	Coagulation factor IX	Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F9	Protease	yes	3.4.21.22	EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right lobe of liver	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F9	45	tissue_specific	marker	right lobe of liver, liver, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
F9	1,451

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F9	P00740	56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective F9 secretion	1	11420.0×	7e-04	F9
Defective gamma-carboxylation of F9	1	5710.0×	7e-04	F9
Defective factor IX causes thrombophilia	1	3806.7×	7e-04	F9
Defective cofactor function of FVIIIa variant	1	3806.7×	7e-04	F9
Defective F9 variant does not activate FX	1	3806.7×	7e-04	F9
Defective F9 activation	1	1903.3×	0.001	F9
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	1268.9×	0.001	F9
Gamma-carboxylation of protein precursors	1	1142.0×	0.001	F9
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	1142.0×	0.001	F9
FXIIa, PKa-dependent activation of coagulation pathway	1	1142.0×	0.001	F9
Amplification and propagation of coagulation cascade	1	634.4×	0.002	F9
Protein hydroxylation	1	543.8×	0.002	F9
Initiation of coagulation cascade	1	475.8×	0.002	F9
Regulation of clotting cascade	1	233.1×	0.004	F9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
zymogen activation	1	674.1×	0.004	F9
blood coagulation	1	173.7×	0.009	F9
proteolysis	1	34.2×	0.029	F9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F9	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LETAXABAN	2	F9
RAZAXABAN	2	F9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
F9	108	Binding:107, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F9	3.4.21.22	coagulation factor IXa

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
F9	108

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
LETAXABAN	2	F9
RAZAXABAN	2	F9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	F9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.