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UniProtKB/Swiss-Prot P00748: Variant p.Thr328Lys

Coagulation factor XII
Gene: F12
Variant information

Variant position:  328
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Threonine (T) to Lysine (K) at position 328 (T328K, p.Thr328Lys).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (T) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Hereditary angioedema 3 (HAE3) [MIM:610618]: A hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). {ECO:0000269|PubMed:16638441, ECO:0000269|PubMed:17186468}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HAE3.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  328
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  615
The length of the canonical sequence.

Location on the sequence:   SPRLHVPLMPAQPAPPKPQP  T TRTPPQSQTPGALPAKREQP
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SPRLHVPLMPAQPAPPKPQPTTRTPPQSQTPG-ALPAKREQP

Mouse                         PLVVPESQEESPSQAPSLSHAPNDSTDHQTS----------

Rat                           SPVSPESHDMLKPRPPILQSSPRDSTRNQNV----------

Pig                           PTQSPSEHQDSPLLSREPQPTTQTPSQNLTSAWCAPPEQRG

Bovine                        PLPSPSALQ-------KPESTTQTPLPSLTSGWCSPT----

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 20 – 372 Coagulation factor XIIa heavy chain
Compositional bias 296 – 349 Pro-rich
Glycosylation 308 – 308 O-linked (GalNAc...) serine
Glycosylation 328 – 328 O-linked (GalNAc...) threonine
Glycosylation 329 – 329 O-linked (GalNAc...) threonine
Glycosylation 337 – 337 O-linked (GalNAc...) threonine


Literature citations

Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor.
Dewald G.; Bork K.;
Biochem. Biophys. Res. Commun. 343:1286-1289(2006)
Cited for: VARIANTS HAE3 LYS-328 AND ARG-328;

Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III.
Cichon S.; Martin L.; Hennies H.C.; Mueller F.; Van Driessche K.; Karpushova A.; Stevens W.; Colombo R.; Renne T.; Drouet C.; Bork K.; Noethen M.M.;
Am. J. Hum. Genet. 79:1098-1104(2006)
Cited for: VARIANT HAE3 LYS-328;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.