F XI Deficiency Mutation Database©
Help Page
  • You can carry out a variety of different searches varying from simply returning the mutations within a domain to complex queries that retrieve mutations of a certain phenotype, amino acid type and from specific authors over a range of domains.
  • The search forms are quite simple and if no fields are filled in the search will return all mutations within the database.
  • The results of each search are shown as a HTML interface, where patient data can either be displayed or omitted at the touch of a button. The results of all searches can be downloaded as an Excel file by clicking the button at the top right hand side of the results page.
  • The quicksearch feature on the home page can be used to retrieve data on mutations for a specific codon number.
Mutation Data
  • The nucleotide description for each mutation includes the nucleotide number, where, following HGVS guidelines c. represents cDNA. Sequences are numbered from +1 starting with the A of the ATG initiation codon, taken from the following files : RefSeq #: NM_000128.2 and GenBank #: AY191837.1.
  • The codon numbers quoted for each mutation in the database are numbered starting from the glutamic acid residue after the 18-residue signal peptide. This is consistent with all previous reports of FXI mutations. HGVS guidelines state the codons should be numbered from the ATG of the initiation codon and should include the signal peptide. This numbering system is displayed next to our numbering system in brackets where appropriate to avoid confusion.
  • The position field describes the location of the residue within the X-ray crystal structure of FXI. They are given as DSSP assignments (B = etc). Cysteine residues are indicated by C followed by a number referring to the order in which the cysteins appear in the sequence of each FXI domain. The 7 conserved Β-strands within each Ap domain of FXI are designated A-G in the order they occur in the sequence and the 9 Β-strands of the SP domain are designated A-O.
Patient Data
  • Patient data can be displayed for each mutation on the results page by using the expand button under the Patient Data column.
  • The patient data in this database is taken where possible from the literature reporting on the mutations. It includes the results of FXI:C and FXI:Ag assays for the reported patients and also has comments on any experimental data on the mutant protein.
  • The Type field indicates the phenotypic classification of the mutation using the reported levels of FXI:Ag from patient plasma.
    • A low level of FXI in plasma indicates a Type I phenotype (CRM-) where the mutant protein is not available in normal amounts, and therefore the mutation must have a structural effect on the mutant protein affecting stability, for example leading to problems with secretion.
    • A normal or high level of FXI in plasma indicates a Type II phenotype (CRM+) where the mutant protein is available in normal amounts, and so must be dysfunctional.
  • A number of the patients are compound heterozygous for different mutations, and this can effect the analysis of these mutations. Wherever this occurs, patient data displays a genotype of CH and the corresponding entry for the other mutation can be displayed.
  • Each patient record has a reference field quoting the reference that originally discussed the patient and mutation. Where mutations do not have patient records - references are quoted in the comments field. References are quoted in full using the reference link and the pubmed entry for the mutation can be displayed be clicking the link.
  • This database used references for three different types of information:
    1. Mutations
    2. Structures
    3. FXI information
    Each reference is quoted under the appropriate heading on the reference page.