Factor IX Gene (F9) Variant Database  

The reference sequence used for FVIII protein is NP_000124.1 and its corresponding stable Locus Reference Genomic DNA sequence (LRG) is LRG_556. 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 46-residue signal peptide/propeptide (this is -46 in Legacy numbering). In Legacy numbering, codon +1 refers to that coding for the first amino-acid of the mature FIX protein (in HGVS numbering, this is codon +47). HGVS numbering is recommended, however Legacy numbering is extensively used in FIX publications, particularly before the year 2000.

Variants causing haemophilia B are classified by factor IX clotting activity level (FIX:C) into the following groups: severe (≤1%), moderate (1-5%) and mild >5%. Where a laboratory value does not correlate with the severity given in a particular report we have attempted to clarify the discrepancy with the original authors. If the discrepancy remains, the clinical severity of the phenotype as reported by the authors has been used. For variants causing mild haemophilia B we have attempted to indicate whether the deleterious effect of the mutation is predominantly quantitative (reduced levels of a normally functioning protein) or qualitative (dysfunctional protein which may or may not also be associated with a reduction in protein level). This is indicated in results tables under the "Type" heading using the conventions used for other coagulation proteins so that Type I refers to quantitative defects with an activity:antigen ratio >0.7 and Type II are qualitative defects with a ratio ≤ 0.7. These categories broadly correspond respectively to the terms CRM (cross-reacting material) negative and positive sometimes found in older publications.

The information contained on this web site is provided for scientific research purposes only. We do not give medical advice or recommend any particular treatment for specific individuals. Click here for patient information.

We are grateful for Dr Peter Green's agreement to use the KCL data as the basis for this updated and upgraded Database: Dr Green at King's College London originated and maintained an extensive database of F9 variants.

This work was supported through a medical educational grant from Pfizer UK Ltd.

We thank the Special Trustees of the Royal Free Hospital and the Katharine Dormandy Trust for Haemophilia and Related Disorders for their support.

We thank the European Association for Haemophilia and Allied Disorders (EAHAD) for supporting our work.

The following people worked on this project:

• Pavithra M Rallapalli, formerly of UCL, London
• Geoffrey Kemball-Cook, The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London
• Edward G. Tuddenham, The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London
• Keith Gomez, The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London
• Stephen J Perkins, UCL, London

If you find this website useful, please reference our F9 DB publication: Rallapalli, P.M., Kemball-Cook, G., Tuddenham, E.G., Gomez, K., & Perkins, S.J. 2013. An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of haemophilia B. J.Thromb.Haemost. available from: PM:23617593
Recent publication on the EAHAD Coagulation Factor Databases:
The European Association for Haemophilia and Allied Disorders (EAHAD) Coagulation Factor Variant Databases: Important resources for haemostasis clinicians and researchers. McVey JH, Rallapalli PM, Kemball-Cook G, Hampshire DJ, Giansily-Blaizot M, Gomez K, Perkins SJ, Ludlam CA.
Access here: Haemophilia. 2020 Mar;26(2):306-313. doi: 10.1111/hae.13947.