Factor XI Variant Database

In Depth Variant Analysis: c.1394C>G (p.Gln451Glu)

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c.1394C>G

p.Gln451Glu (Legacy AA No. 433)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>G

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

Allele Frequency *:

Variant Comments & Reference:

Expected to lead to disruption of the catalytic domain structure of FXI molecule. Gln451 is highly conserved among humans, cattle, mice and dogs, as well as red jungle fowl, which suggests that Gln451 may be crucial for FXI activity. Gln has no charge, while Glu has a net negative charge at physiological pH. The charge change during Gln to Glu substitution may disturb the electrostatic properties of FXI, leading to abnormal activity. Ishikawa et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Other Variants	Severity	Comments	Reference
484	2	M	Japanese	<1	Compound heterozygote	c.1556insG	Severe	No history of episodes of excessive bleeding.	Ishikawa et al 2007
485	4	M	Japanese	4	Compound heterozygote	c.1556insG	Not Reported	Frequent epistaxis.	Ishikawa et al 2007
486	6	F	Japanese	64	Heterozygote		Not Reported		Ishikawa et al 2007
487		M	Japanese	58	Heterozygote		Not Reported	Father of patients 484, 485 and 486. The children's mother is heterozygous for c.1556dupG mutation.	Ishikawa et al 2007

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Gln	-	acyclic	large	surface	hydrophilic	neutral
Mutated	Glu	acidic	acyclic	large	surface	hydrophilic	negative

Substitution Analysis:

Grantham Score : 29

PolyPhen-2 Prediction : Probably Damaging (SCORE: 1.000)

SIFT Prediction : Tolerated (SCORE: 0.44)

PROVEAN Prediction : Neutral (SCORE: -1.542)

Structural Implications:

Gln451 is a buried residue (surface accessibility value = 0 ).

Gln451 is in a region of secondary structure within the FXI domains.

The DSSP assignment for this residue is ... G.

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