Congenital Factor V Deficiency (MONDO:0009210): research report

Verification status. I ran three web searches. They returned review-level sources but no abstract text I could quote, and none of the PMIDs were confirmed. Claims are tagged [sourced] where a search result supports them. Claims tagged [background] come from my own knowledge and have not been checked. The Term Validation and just preflight-dr steps in CLAUDE.md still apply, and so does the rule that every CURIE and PMID is read from a source before it is written. The ontology IDs below are leads, not bindings. I did not look up any of them. Please do not bind them, or quote snippets, without a lookup and just fetch-reference.

1. Disease information

• Congenital factor V (FV) deficiency is a rare autosomal recessive bleeding disorder. It is caused by a deficiency of coagulation factor V (proaccelerin, labile factor). [sourced: NHF/HFA overview]
• Synonyms: Owren's disease, parahemophilia, proaccelerin deficiency, labile factor deficiency. [sourced: same page]
• Identifiers:
• MONDO:0009210, given in the template.
• HGNC:3542 appears in a GenCC submission linking F5 to MONDO:0009210. [sourced: GenCC]
• The repo uses the lowercase form hgnc:3542.
• OMIM 227400 [background, unverified].
• Orphanet number: not found.
• ICD-10 D68.2 (hereditary deficiency of other clotting factors) [background, unverified].
• Do not confuse it with FV Leiden (thrombophilia), combined FV/FVIII deficiency (LMAN1/MCFD2), or acquired FV inhibitors. Combined FV/FVIII deficiency is a separate disease. [background]
• The data are aggregated disease-level resources and case series, not EHR-derived.

2. Etiology

• Causal factor: biallelic loss-of-function variants in F5. [sourced: Asselta & Peyvandi review, 2009] The review reports that 56 mutations had been published in severe or moderately severe FV deficiency. More than two thirds were null mutations, and the rest were mostly missense.
• Heterozygous carriers have about half-normal FV and are usually asymptomatic. [sourced]
• Risk factors:
• Consanguinity raises the chance of homozygosity. [background]
• No environmental risk factors are known.
• Protective factors:
• Platelet-derived FV can partly preserve hemostasis even when plasma FV is near zero. [sourced: Cornell VIVO record, "Platelets and platelet-derived factor Va confer hemostatic competence in complete factor V deficiency"]
• Concurrent thrombophilic variants (e.g. FV Leiden in trans) can attenuate the bleeding phenotype. [background, unverified]
• Gene–environment interactions: none established.

3. Phenotypes

Suggested HPO terms are leads and must be looked up before binding.

• Onset runs from neonatal to adult. The mildest cases are diagnosed late.
• Severity correlates imperfectly with plasma FV activity, and platelet FV helps account for the mismatch.
• The course is lifelong. Bleeding is episodic.
• Frequency percentages and quality-of-life data: not retrieved.

4. Genetic and molecular information

• Gene: F5 (HGNC:3542), at 1q24.2 [background]. The protein is large, with A1-A2-B-A3-C1-C2 domains. [background]
• Variant spectrum: null (nonsense, frameshift, splice) and missense variants spread across the gene. [sourced: 2019 overview]
• Reported case series include an Indian cohort with three novel exon 13 deletions and an African American patient with two novel variants. [sourced via search summary; citations not verified]
• Mechanism: loss of function. [sourced]
• Modifier genes: not established in what I retrieved.
• Epigenetic and chromosomal abnormalities: none known.
• Allele frequencies (gnomAD) and ClinVar classifications: not retrieved.
• Gene-disease validity: GenCC lists an F5–MONDO:0009210 submission. [sourced: GenCC] Run just check-gene-validity and copy the tier from ClinGen. Do not assign one.

5. Environmental information

None are known. There are no environmental, lifestyle, or infectious causes of the congenital form. Acquired FV deficiency (inhibitors, liver disease, DIC) is a separate entity.

6. Mechanism / pathophysiology

Causal chain: 1. Biallelic F5 loss-of-function variants lead to absent or reduced synthesis or secretion of FV. [sourced] 2. FV is made mainly in the liver (hepatocytes) and circulates as plasma FV. About 20% is stored in platelet α-granules. [sourced via search summary; hepatic synthesis is background] 3. Without FV there is no cofactor Va for factor Xa in the prothrombinase complex. Prothrombin conversion to thrombin on activated platelet surfaces is then impaired. [background] 4. Reduced thrombin generation leads to defective fibrin formation, and the PT and aPTT are prolonged. [background] 5. The result is mucosal and postoperative bleeding. The phenotype is variable because platelet FV/Va can partly compensate. [sourced: Cornell VIVO record] 6. Branch: in the most severe genotypes, with absent plasma and platelet FV, intracranial hemorrhage occurs, including perinatally. [sourced: Haematologica]

Suggested terms, to be verified by lookup: - GO: blood coagulation, thrombin generation, prothrombinase complex. - CL: hepatocyte, platelet, megakaryocyte. - GO CC: platelet alpha granule.

There are no single-cell, proteomic, or other omics findings in what I retrieved.

7. Anatomical structures affected

• Systemic hemostasis, with the liver as the site of synthesis. Mucosae (nose, gut, uterus), brain, lung, and joints are the bleeding sites. [sourced / background]
• Subcellular: platelet alpha granule. Laterality: not applicable.

8. Temporal development

• Onset is congenital. The phenotype may present in the neonatal period, in childhood, or in adulthood.
• The course is lifelong, non-progressive, and episodic. Intracranial hemorrhage is the main early-life risk. [sourced]
• No remission patterns are described.

9. Inheritance and population

• Autosomal recessive.
• Prevalence: about 1 in 1,000,000 is the usual figure [background]. A 2025 knock-in mouse paper describes the disease as ultra-rare, "1–9 cases per million live births". [sourced: PMC12129228] Reconcile the two against Orphanet before choosing a prevalence_class. I found no Orphanet page.
• Carrier frequency: not retrieved.
• Consanguinity increases the disease frequency. [background]
• Founder effects: I did not retrieve any; the Indian cohort exon 13 deletions are a lead. Sex ratio is expected to be equal, as expected for autosomal inheritance. [background]

10. Diagnostics

• Prolonged PT and aPTT with a normal thrombin time. A mixing study corrects. [background]
• FV activity assay, which is diagnostic. FV antigen can distinguish type I (quantitative) from type II (qualitative) deficiency. [background]
• Heterozygotes have about 50% FV. [sourced]
• Genetic testing: F5 sequencing, which is large and requires Sanger sequencing, a panel, or exome sequencing. [background]
• Differential: combined FV/FVIII deficiency (LMAN1/MCFD2), acquired FV inhibitor, liver disease, vitamin K deficiency, DIC. [background]
• Screening: none population-wide. Cascade testing of relatives is relevant.
• GeneReviews chapter: not found in my search. Run just check-genereviews.

11. Outcome / prognosis

• Bleeding severity is variable. Most patients have mucosal bleeding that is managed with treatment. Severe cases can involve life-threatening intracranial, pulmonary, or GI hemorrhage. [sourced]
• Survival and life-expectancy data: not retrieved.
• Prognostic factors: FV activity level and genotype, with platelet FV as a modifier. [sourced / background]

12. Treatment

• There is no FV-specific concentrate. Fresh frozen plasma (FFP) is the mainstay. [sourced: Rare Coagulation Disorders; NHF/HFA overview]
• Dosing: one review sets a target of FV above 20% for procedures and acute bleeding, with daily FFP infusions of 15–20 mL/kg typically enough. [sourced via search summary; verify at the source]
• Platelet transfusion is added in severe or refractory bleeding. Platelet FV supports hemostasis after plasma infusion. [sourced: Cornell VIVO record]
• Antifibrinolytics (aminocaproic acid or tranexamic acid) are used for mucosal bleeding. rFVIIa and prothrombin complex concentrate have been used in refractory cases. [sourced via search summary]
• Experimental: a 2025 Thieme article, "From Fresh Frozen Plasma to First-in-human: Bringing Coagulation Factor V Deficiency into Therapeutic Trials", covers development of FV therapeutics, but I did not read it. [sourced: Thieme] I found no NCT identifiers.
• NCIT leads to look up and not bind from memory: Pharmacotherapy (NCIT:C15986), Supportive Care (NCIT:C15747), and a plasma or blood transfusion term.
• For the KB, use therapeutic_modality: PROTEIN_REPLACEMENT for FFP, only after a source check.

13. Prevention

• No primary prevention.
• Genetic counseling and cascade testing apply. Prenatal diagnosis is possible in families with a known variant. [background]
• Prophylactic FFP before surgery or procedures is used as secondary and tertiary prevention. Peripartum and neonatal management planning is needed in severe cases. [background]
• Avoid antiplatelet drugs. [background, unverified]

14. Other species

• I did not search OMIA. Naturally occurring FV deficiency has been described in animals. I have not verified it and would not cite it without a source.

15. Model organisms

• F5 knockout mice: about half die at E9–E10 with yolk-sac vascular and somite defects. The rest are born and die of massive hemorrhage within hours of birth. [sourced: PMC4260973 table T3; UMich listing] The primary paper is probably Cui et al. 1996. That attribution is a lead and not confirmed.
• A 2025 knock-in model is viable and was developed for an ultra-rare disease. [sourced: PMC12129228]
• A truncated mutant FV mouse affected hemostasis and embryonic development. [sourced: UCM record]
• The null mouse is much more severe than most human cases, because human partial or platelet FV and residual variants soften the phenotype. This fits HUMAN_MODEL_MISMATCH or a PARTIALLY_RECAPITULATES link. [background]

Sources

• Asselta & Peyvandi review (identified from the QxMD record; PMID not verified)
• 2019 overview
• 2024 review
• Haematologica, splicing mutations and intracranial bleeding
• NHF/HFA overview
• Rare Coagulation Disorders
• Cornell VIVO, platelet FV
• GenCC
• PMC12129228
• PMC4260973
• Thieme therapeutic trials article

Reference Validation

Checked with linkml-reference-validator 0.3.0.

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

3 of 4 terms resolved to a current term; the rest could not be looked up either way.