UniProtKB/Swiss-Prot Q9Y6X0: Variant p.Ile871Thr

SET-binding protein
Gene: SETBP1
Chromosomal location: 18q21.1
Variant information

Variant position:  871
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Isoleucine (I) to Threonine (T) at position 871 (I871T, p.Ile871Thr).
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:  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. 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.

Involvement in disease:  Schinzel-Giedion midface retraction syndrome (SGMFS) [MIM:269150]: A disorder characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia. 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 SGMFS and ACML; somatic mutation in ACML and other myeloid malignancies.
Any additional useful information about the variant.



Sequence information

Variant position:  871
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:   ITLSPVSESHSEETIPSDSG  I GTDNNSTSDQAEKSSESRRR
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                         ITLSPVSESHSEETIPSDSGIGTDNNSTSDQAEKSSESRRR

Mouse                         ITLSPVSESHSEETIPSDSGIGTDNNSTSDQAEKSSESRRR

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


Literature citations

De novo mutations of SETBP1 cause Schinzel-Giedion syndrome.
Hoischen A.; van Bon B.W.; Gilissen C.; Arts P.; van Lier B.; Steehouwer M.; de Vries P.; de Reuver R.; Wieskamp N.; Mortier G.; Devriendt K.; Amorim M.Z.; Revencu N.; Kidd A.; Barbosa M.; Turner A.; Smith J.; Oley C.; Henderson A.; Hayes I.M.; Thompson E.M.; Brunner H.G.; de Vries B.B.; Veltman J.A.;
Nat. Genet. 42:483-485(2010)
Cited for: VARIANTS SGMFS ASN-868; ALA-868; ASP-870; SER-870 AND THR-871;

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;

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.