Defective F9 activation

Stable Identifier
Homo sapiens
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Deficiency or dysfunction of FIX leads to hemophilia B (HB), an X-linked, recessive, bleeding disorder. On a molecular basis, HB is due to a heterogeneous spectrum of mutations spread throughout the F9 gene (Rallapalli PM et al. 2013).

The Reactome event describes the defective proteolytic activation of FIX by factor XIa due to the presence of HB-associated point mutations R191C, R191H, R226Q and R226W in the cleavage sites of FIX (Liddell MB et al. 1989; Monroe DM et al. 1989; Suehiro K et al. 1989; Diuguid DL et al. 1989; Bertina RM et al.1990). In addition, naturally occurring point mutations in the FIX propeptide sequence such as N43Q, N43L or N46S are also annotated here. These FIX variants are secreted into the circulation with a mutant 18-amino acid propeptide still attached (Bentley AK et al. 1986; Galeffi P & Brownlee GG 1987). The unprocessed FIX variants were found to affect the function of the protein by destabilizing the calcium-induced conformation of FIX (Wojcik EG et al. 1997) and showed delayed activation by FXIa (Liddell MB et al. 1989; Ware J et al. 1989; de la Salle C et al. 1993; Wojcik EG et al. 1997; Bristol JA et al. 1993).

Literature References
PubMed ID Title Journal Year
2738071 Factor IX San Dimas. Substitution of glutamine for Arg-4 in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties.

Furie, B, Stafford, DW, Diuguid, DL, Liebman, HA, Rabiet, MJ, Ware, J, Kasper, CK, Furie, BC

J Biol Chem 1989
2775660 Factor IX Cardiff: a variant factor IX protein that shows abnormal activation is caused by an arginine to cysteine substitution at position 145

Giddings, JC, Bloom, AL, Peake, IR, Lillicrap, DP, Taylor, SA, Liddell, MB

Br. J. Haematol. 1989
2713493 Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo

Lundblad, RL, Roberts, HR, McCord, DM, High, KA, Huang, MN, Kasper, CK, Monroe, DM

Blood 1989
2592373 Blood clotting factor IX BM Nagoya. Substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase

Niho, Y, Suehiro, K, Saito, H, Ogata, K, Takeya, H, Kawabata, S, Kamiya, T, Miyata, T, Iwanaga, S, Takamatsu, J

J. Biol. Chem. 1989
3009023 Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4

Bentley, AK, Brownlee, GG, Rizza, C, Rees, DJ

Cell 1986
2788012 Defective propeptide processing and abnormal activation underlie the molecular pathology of factor IX Troed-y-Rhiw

Bloom, AL, Peake, IR, Lillicrap, DP, Liddell, MB

Br. J. Haematol. 1989
Name Identifier Synonyms
hemophilia B DOID:12259 factor IX deficiency, Congenital factor IX deficiency, deficiency, functional factor IX, Congenital factor IX disorder
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