Factor XI Variant Database

In Depth Variant Analysis: c.1288G>A (p.Ala430Thr)

Terms with a '*' next to them are explained on the Help Page .

c.1288G>A

p.Ala430Thr (Legacy AA No. 412)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

282590

Allele Frequency *:

0.000071

Variant Comments & Reference:

Ala430 is located in an alpha helix portion. Substitution at this position with Thr is expected to disrupt the helix structure due to steric constraints from the neighbouring residues Phe433 and Tyr434. The introduction of a polar residue in place of the simple aliphatic side chain of Ala is likely to perturb the local folding of the protein. Homology modelling suggests that this substitution might impair FXI secretion by reducing the stability of the serine protease fold. de Raucourt et al 2008, Castaman et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
413	23	F	French	0.07	0.07	Compound heterozygote		Severe	Menorrhagia, gingivorrhagia and easy bruising. Dental extractions under tranexamic acid cover associated with post-procedural excessive bleeding. APTT 55 sec, Blood Group O.	de Raucourt et al 2008
476	23	F	French	0.07	0.07	Compound heterozygote	c.596C>T (p.Ala199Val)	Severe	Menorrhagia, gingivorrhagia and easy bruising. Dental extractions under tranexamic acid cover associated with post-procedural excessive bleeding. APTT 55 sec, Blood Group O.	de Raucourt et al 2008
477	40	F	Czech	2	2	Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported	Epistaxis, post-operative bleeding and bleeding following tooth extraction. Patient also suffers from menorrhagia and experienced postpartum bleeding.	Castaman et al 2008

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Ala	aliphatic	acyclic	small	buried	hydrophobic	neutral
Mutated	Thr	-	acyclic	medium	surface	hydrophilic	neutral

Substitution Analysis:

Grantham Score : 58

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

SIFT Prediction : Probably Damaging (SCORE: 0.01)

PROVEAN Prediction : Deleterious (SCORE: -3.251)

Structural Implications:

Ala430 is a buried residue (surface accessibility value = 0 ).

Ala430 is in a region of secondary structure within the FXI domains.

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

Hint: Left click mouse | To rotate the structure
Hint: Rotate mousewheel | To zoom in/out the structure
Hint: Right click mouse | to use applet control options

Controls

The molecule can be rotated with the mouse holding the left button and the image can be magnified using the middle mouse button.

Right Click on the JMOL screen for more options.

Options

Spacefill
Cartoon
Wireframe
Trace
Backbone
Spin
Background
Disulphides
Domains
Alternative Colouring
Labels

Right Click on the molecule's screen for more options.

NOTE: If no Java applet appears or a Java error message is shown, please click the following LINK.

Please click here to view the Database Statistics