UniProtKB/SwissProt variant VAR

Variant information

Variant position:

858

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 Glutamate (E) to Lysine (K) at position 858 (E858K, p.Glu858Lys).

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 acidic (E) 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:

Leukemia, chronic myeloid, atypical (ACML) [MIM:608232]: A myeloproliferative disorder that shares clinical and laboratory features with chronic myeloid leukemia but lacks the pathognomonic Philadelphia chromosome and the corresponding BCR/ABL1 fusion transcript. Features include myeloid predominance in the bone marrow, myeloid proliferation and low leukocyte alkaline phosphatase value, splenomegaly, hepatomegaly, elevated white blood cell count. Enlarged spleen may also be associated with a hypermetabolic state, fever, weight loss, and chronic fatigue. The enlarged liver may contribute to the patient's weight loss. {ECO:0000269|PubMed:23222956}. Note=The gene represented in this entry is involved in disease pathogenesis.

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 ACML; somatic mutation in ACML and other myeloid malignancies.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1178702025 [ dbSNP | Ensembl ]

Sequence information

Variant position:

858

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

Protein sequence length:

1596

The length of the canonical sequence.

Location on the sequence:

SPSHLCEIGSLKEITLSPVS E SHSEETIPSDSGIGTDNNST

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                         SPSHLCEIGSLKEITLSPVSESHSEETIPSDSGIGTDNNST

Mouse                         SPSHLCEIGSLKEITLSPVSESHSEETIPSDSGIGTDNNST

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	1 – 1596	SET-binding protein
Alternative sequence	243 – 1596	Missing. In isoform 2.

Literature citations

SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations.
Meggendorfer M.; Bacher U.; Alpermann T.; Haferlach C.; Kern W.; Gambacorti-Passerini C.; Haferlach T.; Schnittger S.;
Leukemia 27:1852-1860(2013)
Cited for: VARIANTS MYELOID MALIGNANCIES LYS-858; ASN-868; TYR-868; GLY-868; ARG-869; SER-870; ASP-870; VAL-870; THR-871; ARG-873; ASN-874 AND ASN-908;

Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.
Piazza R.; Valletta S.; Winkelmann N.; Redaelli S.; Spinelli R.; Pirola A.; Antolini L.; Mologni L.; Donadoni C.; Papaemmanuil E.; Schnittger S.; Kim D.W.; Boultwood J.; Rossi F.; Gaipa G.; De Martini G.P.; di Celle P.F.; Jang H.G.; Fantin V.; Bignell G.R.; Magistroni V.; Haferlach T.; Pogliani E.M.; Campbell P.J.; Chase A.J.; Tapper W.J.; Cross N.C.; Gambacorti-Passerini C.;
Nat. Genet. 45:18-24(2013)
Cited for: VARIANTS ACML LYS-858; ASN-868; SER-870 AND THR-871; VARIANTS HIS-1321 AND LEU-1377; CHARACTERIZATION OF VARIANT ACML SER-870;

UniProtKB/Swiss-Prot Q9Y6X0: Variant p.Glu858Lys