Factor X Gene (F10) Variant Database  

Two previous EAHAD-DB coagulation factor databases (X-linked F8 and F9) have the benefit of simplicity bestowed by each case only having a single allele to consider, and in the vast majority of cases with only a single variant detected: cases are therefore listed synonymously with their variant, on a single line of a spreadsheet or tabular output. However there are several features of F10 which require that a DB of F10 variants be treated differently from variants in the X-linked F8 and F9 DBs:

• The F10 DB must consider both alleles in a case instead of just a single allele
• Cases may have more than one F10 variant, each in the heterozygous or homozygous state
• There is more than one functional assay for plasma FX activity
• the relationship between variants, circulating FX protein levels and clinical bleeding severity in cases is far from simple

This has led to different data organisation and display for the F10 DB. For each case, every variant (i.e. every divergence from the deposited Reference Sequence) is stored separately but linked to the case, together with its genotype (heterozygous or homozygous). Every case has a unique Case No., and every Variant also has a unique Variant No.

The reference sequence used for FX protein is NP_000495.1 and its corresponding stable Locus Reference Genomic DNA sequence (LRG) is LRG_548. Codons and amino-acids are numbered on this site in two ways. In HGVS Numbering , codons are numbered with codon +1 coding for the first residue (Met) of the 40-residue signal peptide/propeptide (this is -40 in Legacy numbering). In Legacy numbering, codon +1 refers to that coding for the first amino-acid of the mature FX protein (in HGVS numbering, this is codon +41). HGVS numbering is recommended, however Legacy numbering is included on this site, as it was often used in FX publications, particularly before the year 2010.

From the Advanced Search Page you can carry out a variety of different searches varying from simply returning the variants recorded at an amino-acid position or within a FX domain, to complex queries that retrieve variants (for example) of a given type or phenotype, amino acid type or from a specific publication. NOTE: if no fields or checkboxes are filled in, the search will return ALL variants within the F10 variant database. This can be useful as an initial stage before further sorting.

The results of each Advanced Search can be viewed mainly in three different ways. It’s the same data, but you may prefer different methods depending on your purpose.

1. After pressing Search, variants are simply listed in cDNA order with brief details and live links to case information as well as (for missense variants) structural implications and informative amino-acid alignments
2. By clicking the “Multiple/Screen Table” link at the top of the Results page, a detailed screen table of all individual case/variant reports (in cDNA order) is displayed: many items in the table are sortable (including Case No), individual values can be typed in to isolate data, and there are direct links to Case Pages (see below)
3. By clicking the “Unique/Screen Table” link at the top of the Results page, a summary screen table of all unique variants (in cDNA order) are displayed: many items in the table are sortable (including Variant No), individual values can be typed in to isolate data, and there are direct links to Variant Pages (see below) In addition, CSV outputs similar to the Multiple and Unique screen displays can be downloaded for DB users to sort as you will (for example in MS Excel).

Every variant found in a case is linked to that case, and every case has a unique Case No. Whenever the Case No. value in a tabular display is clicked, it links to a summary Case Page which lists the phenotypic data in that case at the top of the page, and details of all the variants found in tabular form below.

In the DB every variant also has a unique Variant No. Whenever the Variant No. value in a tabular display is clicked, it links to a summary Variant Page which lists the genetic data in that variant at the top of the page, and details of all the individual cases in which the variant is found in tabular form below.

There are a number of polymorphisms found in F10 case genotyping, however unlike the situation with some other coagulation factors (for example factors V and VII), these polymorphisms do not appear to be associated with modulation of circulating FX levels. They are therefore not currently listed in this EAHAD database.

Within the DB each case is linked to the publication that described the case and its associated genetic and phenotypic data. All case entries in the various displays have links to the relevant PubMed abstract where available.

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