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c.1165G>A
p.Val389Ile (Legacy AA No. 371)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
II
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Residue Val389 is located one
residue following the cleavage site of FXI (P2' position,
according to the convention of numbering position
around the scissile bond), thus is part of the
activation loop. FXI antigen levels, measured in both conditioned media and lysates of cells expressing the
mutant protein (in either the heterozygous or homozygous state), were not significantly different from those
measured in wild-type samples. FXI specific activity was measured in conditioned
media.
The specific activity of the FXI Val389Ile protein was significantly reduced when compared with the wildtype one (30% and 80% for the heterozygous and the
homozygous conditions, respectively). Given the proximity of
Val389 to the FXI activation site, a possible interference
on FXI activation was hypothesized and this mutation was found to be associated with a defect
both in FXI activation (slower than normal), and in
FIX activation (slightly delayed), thus supporting the
role of residues neighboring the active site in influencing
and stabilizing the enzyme active state. Bozzao et al 2007
Asymptomatic.
Appendectomy, adenoidectomy and right knee arthroscopy had been without mishap. Patient's mother, born 1949, also had reduced FXI:C (43%) associated with normal FXI:Ag (132%), whereas the father, born 1947, had both functional and antigen FXI levels within normal range (96 and 134%, respectively).Mother had same Val371Ile in heterozygous state. Both parents were asymptomatic.
