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UniProtKB/Swiss-Prot Q8NI22: Variant p.Ile136Thr

Multiple coagulation factor deficiency protein 2
Gene: MCFD2
Variant information

Variant position:  136
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 Isoleucine (I) to Threonine (T) at position 136 (I136T, p.Ile136Thr).
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 hydrophobic (I) to medium size and polar (T)
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:  Factor V and factor VIII combined deficiency 2 (F5F8D2) [MIM:613625]: A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal. {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:18590741, ECO:0000269|PubMed:18685427, ECO:0000269|PubMed:20491958}. 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 F5F8D2; interferes with protein folding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  136
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  146
The length of the canonical sequence.

Location on the sequence:   ELINIIDGVLRDDDKNNDGY  I DYAEFAKSLQ
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                         ELINIIDGVLRDDDKNNDGYIDYAEFAKSLQ

Mouse                         ELVSIIDGVLRDDDKNNDGYIDYAEFAKSLQ

Rat                           ELISIIDGVLRDDDKNNDGYIDYAEFAKSLQ

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 27 – 146 Multiple coagulation factor deficiency protein 2
Domain 116 – 146 EF-hand 2
Calcium binding 129 – 140 2
Beta strand 133 – 137


Literature citations

Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex.
Zhang B.; Cunningham M.A.; Nichols W.C.; Bernat J.A.; Seligsohn U.; Pipe S.W.; McVey J.H.; Schulte-Overberg U.; de Bosch N.B.; Ruiz-Saez A.; White G.C.; Tuddenham E.G.; Kaufman R.J.; Ginsburg D.;
Nat. Genet. 34:220-225(2003)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); SUBCELLULAR LOCATION; INTERACTION WITH LMAN1; FUNCTION; VARIANTS F5F8D2 GLU-129 AND THR-136;

New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2.
Guy J.E.; Wigren E.; Svaerd M.; Haerd T.; Lindqvist Y.;
J. Mol. Biol. 381:941-955(2008)
Cited for: STRUCTURE BY NMR OF 27-146; DOMAIN; CHARACTERIZATION OF VARIANTS F5F8D2 GLU-129 AND THR-136; CALCIUM-BINDING;

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.