Factor XI Variant Database

In Depth Variant Analysis: c.1478C>T (p.Thr493Ile)

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

c.1478C>T

p.Thr493Ile (Legacy AA No. 475)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

Allele Frequency *:

Variant Comments & Reference:

Expression of mutant protein shows mutant is secreted poorly compared to wild type. This mutation destroys an N-linked glycosylation site. Substitution of Thr493 with Ala, Pro, Lys or Arg all abolish the site and also severely reduce level of secreted FXI:Ag. Substitution with Ser which does not abolish the site had no affect on secretion. However substitution of Asn491 with Ala which abolishes the glycosylation site also had no affect on secretion. This indicates the cause of failure to secrete FXI is not the loss of glycolsylation site. McVey et al 2005

Patient Information: Show

Patient_ID	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
46					Heterozygote	Mild		Bolton-Maggs et al 2003 Abstract
164	M	Non-Jewish	39	27	Heterozygote	Mild	Asymptomatic microscopic haematuria identified at medical examination, age 14. Bleed for 2 days following tooth extraction.	McVey et al 2005
255		UK Population	46		Heterozygote	Not Reported		Mitchell et al 2006

Residue Information:

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

Substitution Analysis:

Grantham Score : 89

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

SIFT Prediction : Probably Damaging (SCORE: 0.00)

PROVEAN Prediction : Deleterious (SCORE: -4.025)

Structural Implications:

Thr493 is an exposed residue (surface accessibility value = 3 ).

Thr493 is in a random coil area of the FXI structure.

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

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