UniProtKB/SwissProt variant VAR

Variant information

Variant position:

247

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 247 (I247T, p.Ile247Thr).

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:

Anhaptoglobinemia (AHP) [MIM:614081]: A condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions. {ECO:0000269|PubMed:14999562}. 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 AHP; causes reduced expression of the protein.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894517 [ dbSNP | Ensembl ]

Sequence information

Variant position:

247

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

Protein sequence length:

406

The length of the canonical sequence.

Location on the sequence:

KKQLVEIEKVVLHPNYSQVD I GLIKLKQKVSVNERVMPICL

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                         KKQLVEIEKVVLHPNYSQVDIGLIKLKQKVSVNERVMPICL

                              KNQLVEVEKVVLHPDYSKVDIGLIKLKQKVPIDERVMPICL

Mouse                         KNQLVEIEKVVLHPNHSVVDIGLIKLKQRVLVTERVMPICL

Rat                           KNQLVEIEKVVLHPERSVVDIGLIKLKQKVLVTEKVMPICL

Pig                           KKQEVEIEKVIFHPDNSTVDIGLIKLKQKVPVNERVMPICL

Bovine                        KNQLVEVEKVVLHPDHSKVDIGLIKLRQKVPVNDKVMPICL

Rabbit                        RRQLVEIEKVVLHPNYSEVDIGLIKLKDKVPVNERVMPICL

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.

Type	Positions	Description
Chain	19 – 406	Haptoglobin
Chain	162 – 406	Haptoglobin beta chain
Domain	162 – 404	Peptidase S1
Glycosylation	241 – 241	N-linked (GlcNAc...) (complex) asparagine
Disulfide bond	149 – 266	Interchain (between alpha and beta chains)

Literature citations

A novel I247T missense mutation in the haptoglobin 2 beta-chain decreases the expression of the protein and is associated with ahaptoglobinemia.
Teye K.; Quaye I.K.; Koda Y.; Soejima M.; Pang H.; Tsuneoka M.; Amoah A.G.; Adjei A.; Kimura H.;
Hum. Genet. 114:499-502(2004)
Cited for: VARIANT AHP THR-247; CHARACTERIZATION OF VARIANT AHP THR-247;

UniProtKB/Swiss-Prot P00738: Variant p.Ile247Thr