ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
  • Haploinsufficiency Phenotype: FACTOR V DEFICIENCY
Evidence for haploinsufficiency phenotype
PubMed ID Description
11435304 van Wijik et al report three patients with factor V deficiency diagnosed based on bleeding events or a family history of bleeding events and significantly reduced FV activity in the proband. They sequenced the F5 gene and found that one patient was homozygous for a nonsense variant, one was homozygous for a frameshift variant, and one was compound heterozygous for a frameshift and missense variant. The authors also summarize the findings for nine previously published patients with severely reduced FV activity and bi-allelic F5 variants including three nonsense, four frameshift, and two missense variants.
19598066 Peyvandi and Asselta review factor V deficiency. They mention that >2/3 of previously published mutations are null variants and that heterozygous carriers have half-normal FV activity, but are usually asymptomatic.

Haploinsufficiency phenotype comments:

Individuals with biallelic loss-of-function variants in the F5 gene have factor V deficiency. Factor V Leiden Thrombophila is caused by the presence of the Arg506Gln missense change (either one or two copies), which renders the protein resistant to cleavage by the activated protein C (see GeneReviews PMID 20301542).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No duplications involving only the entire F5 gene reported