factor V deficiency

Summary

factor V deficiency (MONDO:0020586) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 254

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	factor V deficiency
Mondo ID	MONDO:0020586
MeSH	D005166
NCIT	C131738
SNOMED CT	4320005
UMLS	C4317320
MedGen	1369551
GARD	0025179
Is cancer (heuristic)	no

Also known as: factor V deficiency

Data availability: 254 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (27): factor XIII deficiency, factor VII deficiency, factor X deficiency, thrombophilia due to activated protein C resistance, hypoplasminogenemia, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, Tatsumi factor deficiency, East Texas bleeding disorder, 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 fibrinogen deficiency, combined deficiency of factor V and factor VIII, hemophilia, acquired coagulation factor deficiency, von Willebrand disease (hereditary or acquired), factor V short isoforms-related bleeding disorder, factor V amsterdam bleeding disorder, factor V atlanta bleeding disorder, combined deficiency of factor VII and factor X, plasminogen deficiency, type II, dysplasminogenemia

Subtypes (2): congenital factor V deficiency, acquired factor V 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

254 retrieved; paginated sample, class counts are floors:

100 uncertain significance, 70 conflicting classifications of pathogenicity, 45 benign/likely benign, 11 pathogenic, 9 benign, 7 likely pathogenic, 6 pathogenic/likely pathogenic, 5 likely benign, 1 drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098461	NM_000130.5(F5):c.2615del (p.Arg872fs)	F5	Pathogenic	criteria provided, single submitter
1703833	NM_000130.5(F5):c.5403del (p.Lys1801fs)	F5	Pathogenic	criteria provided, single submitter
2444143	NM_000130.5(F5):c.2521C>T (p.Gln841Ter)	F5	Pathogenic	criteria provided, single submitter
293622	NM_000130.5(F5):c.2218C>T (p.Arg740Ter)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627051	NM_000130.5(F5):c.2862del (p.Ser955fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627222	NM_000130.5(F5):c.1297-2A>G	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627264	NM_000130.5(F5):c.1830_1831dup (p.His611fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627287	NM_000130.5(F5):c.2539del (p.Ile847fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627332	NM_000130.5(F5):c.5365C>T (p.Arg1789Ter)	F5	Pathogenic	criteria provided, single submitter
646	NM_000130.5(F5):c.3924_3927del (p.Ser1308fs)	F5	Pathogenic	no assertion criteria provided
647	NM_000130.5(F5):c.4699_4702dup (p.Ala1568fs)	F5	Pathogenic	no assertion criteria provided
648	NM_000130.5(F5):c.1042_1049del (p.Lys348fs)	F5	Pathogenic	no assertion criteria provided
649	NM_000130.5(F5):c.5189A>G (p.Tyr1730Cys)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
650	NM_000130.5(F5):c.2401C>T (p.Gln801Ter)	F5	Pathogenic	criteria provided, single submitter
651	NM_000130.5(F5):c.3481C>T (p.Arg1161Ter)	F5	Pathogenic	no assertion criteria provided
653	NM_000130.5(F5):c.5403_5404insG (p.Ser1802fs)	F5	Pathogenic	no assertion criteria provided
978216	NM_000130.5(F5):c.4096del (p.Leu1366fs)	F5	Pathogenic	criteria provided, single submitter
1098459	NM_000130.5(F5):c.3577del (p.Gln1192_Val1193insTer)	F5	Likely pathogenic	criteria provided, single submitter
1703832	NM_000130.5(F5):c.696C>A (p.Tyr232Ter)	F5	Likely pathogenic	criteria provided, single submitter
1803213	NM_000130.5(F5):c.1673A>G (p.Tyr558Cys)	F5	Likely pathogenic	criteria provided, single submitter
627013	NM_000130.5(F5):c.1671G>C (p.Trp557Cys)	F5	Likely pathogenic	criteria provided, single submitter
627300	NM_000130.5(F5):c.3170_3174del (p.Asn1057fs)	F5	Likely pathogenic	criteria provided, single submitter
654	NM_000130.5(F5):c.6304C>T (p.Arg2102Cys)	F5	Likely pathogenic	criteria provided, single submitter
666966	NM_000130.5(F5):c.1674C>A (p.Tyr558Ter)	F5	Likely pathogenic	criteria provided, single submitter
642	NM_000130.4(F5):c.1601G>A (p.Arg534Gln)	F5	drug response	reviewed by expert panel
255209	NM_000130.5(F5):c.5177G>A (p.Arg1726Gln)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293550	NM_000130.5(F5):c.*1290G>A	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293557	NM_000130.5(F5):c.*838T>C	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293560	NM_000130.5(F5):c.*581C>A	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
293574	NM_000130.5(F5):c.6360G>A (p.Lys2120=)	F5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F5	Orphanet:131	Budd-Chiari syndrome
F5	Orphanet:326	Congenital factor V deficiency
F5	Orphanet:329217	Cerebral sinovenous thrombosis
F5	Orphanet:391320	East Texas bleeding disorder
F5	Orphanet:599579	Factor V Amsterdam bleeding disorder
F5	Orphanet:600194	Factor V Atlanta bleeding disorder
LMAN1	Orphanet:35909	Combined deficiency of factor V and factor VIII

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
F5	HGNC:3542	ENSG00000198734	P12259	Coagulation factor V	clinvar
LMAN1	HGNC:6631	ENSG00000074695	P49257	Protein ERGIC-53	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F5	Coagulation factor V	Central regulator of hemostasis.
LMAN1	Protein ERGIC-53	Mannose-specific lectin.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F5	Other/Unknown	no		FA58C, Cupredoxin, Galactose-bd-like_sf
LMAN1	Other/Unknown	no		Lectin_leg, ConA-like_dom_sf, Intracellular_Lectin-GPT

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
choroid plexus epithelium	1
liver	1
right lobe of liver	1
germinal epithelium of ovary	1
gingival epithelium	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F5	206	broad	marker	right lobe of liver, liver, choroid plexus epithelium
LMAN1	280	ubiquitous	marker	germinal epithelium of ovary, jejunal mucosa, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMAN1	2,474
F5	1,754

Intra-cohort edges

A	B	Sources
F5	LMAN1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F5	P12259	18
LMAN1	P49257	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cargo concentration in the ER	2	335.9×	2e-04	F5, LMAN1
COPII-mediated vesicle transport	2	163.1×	5e-04	F5, LMAN1
Defective cleavage of FV variant at a.a.534	1	1903.3×	0.004	F5
Defective cleavage of FV variant at R334	1	1903.3×	0.004	F5
Amplification and propagation of coagulation cascade	1	317.2×	0.017	F5
Initiation of coagulation cascade	1	237.9×	0.019	F5
Regulation of clotting cascade	1	116.5×	0.033	F5
RHOD GTPase cycle	1	102.0×	0.033	LMAN1
RHOG GTPase cycle	1	74.2×	0.035	LMAN1
RHOC GTPase cycle	1	73.2×	0.035	LMAN1
ER to Golgi Anterograde Transport	1	66.4×	0.035	LMAN1
RAC2 GTPase cycle	1	63.4×	0.035	LMAN1
RAC3 GTPase cycle	1	59.5×	0.035	LMAN1
Transport to the Golgi and subsequent modification	1	51.4×	0.036	LMAN1
Post-translational protein phosphorylation	1	50.1×	0.036	F5
Platelet degranulation	1	43.9×	0.037	F5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.037	F5
RHOA GTPase cycle	1	37.3×	0.040	LMAN1
Asparagine N-linked glycosylation	1	30.1×	0.045	LMAN1
RHO GTPase cycle	1	30.1×	0.045	LMAN1
Membrane Trafficking	1	18.5×	0.066	LMAN1
Vesicle-mediated transport	1	17.4×	0.066	LMAN1
Signaling by Rho GTPases	1	17.1×	0.066	LMAN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.066	LMAN1
Post-translational protein modification	1	9.6×	0.110	LMAN1
Metabolism of proteins	1	6.2×	0.161	LMAN1
Signal Transduction	1	5.1×	0.187	LMAN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	173.7×	4e-04	F5, LMAN1
positive regulation of organelle organization	1	2808.7×	0.001	LMAN1
response to vitamin K	1	2808.7×	0.001	F5
obsolete negative regulation of protein targeting to mitochondrion	1	1404.3×	0.002	LMAN1
blood circulation	1	255.3×	0.009	F5
endoplasmic reticulum organization	1	210.7×	0.009	LMAN1
endoplasmic reticulum to Golgi vesicle-mediated transport	1	68.0×	0.020	LMAN1
Golgi organization	1	66.9×	0.020	LMAN1
protein folding	1	51.7×	0.024	LMAN1
in utero embryonic development	1	36.0×	0.030	LMAN1
protein transport	1	21.9×	0.045	LMAN1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
F5	EDOXABAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F5	2	4
LMAN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EDOXABAN	4	F5
RAZAXABAN	2	F5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
F5	10	Binding:10
LMAN1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
EDOXABAN	4	F5
RAZAXABAN	2	F5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	F5
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	1	LMAN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LMAN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.