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UniProtKB/Swiss-Prot O60674: Variant p.Val617Phe

Tyrosine-protein kinase JAK2
Gene: JAK2
Variant information

Variant position:  617
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 Valine (V) to Phenylalanine (F) at position 617 (V617F, p.Val617Phe).
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 (V) to large size and aromatic (F)
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:  Thrombocythemia 3 (THCYT3) [MIM:614521]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. {ECO:0000269|PubMed:16325696, ECO:0000269|PubMed:22397670}. Note=The disease may be 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.

Involvement in disease:  Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:16247455}. 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.

Involvement in disease:  Polycythemia vera (PV) [MIM:263300]: A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. {ECO:0000269|PubMed:15781101, ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, ECO:0000269|PubMed:16603627}. 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 PV, THCYT3 and AML; associated with susceptibility to Budd-Chiari syndrome; somatic mutation in a high percentage of patients with essential thrombocythemia or myelofibrosis; leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  617
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1132
The length of the canonical sequence.

Location on the sequence:   AASMMSKLSHKHLVLNYGVC  V CGDENILVQEFVKFGSLDTY
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                         AASMMSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTY

Mouse                         AASMMSQLSHKHLVLNYGVCVCGEENILVQEFVKFGSLDTY

Rat                           AASMMSQLSHKHLVLNYGVCVCGEENILVQEFVKFGSLDTY

Pig                           AASMMSQLSHKHLVLNYGVCVCGEENILVQEFVKFGSLDTY

Chicken                       AASMMSQLSYKHLVLNYGVCVCGEENILVQEYVKFGSLDTY

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 – 1132 Tyrosine-protein kinase JAK2
Domain 545 – 809 Protein kinase 1


Literature citations

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.
Baxter E.J.; Scott L.M.; Campbell P.J.; East C.; Fourouclas N.; Swanton S.; Vassiliou G.S.; Bench A.J.; Boyd E.M.; Curtin N.; Scott M.A.; Erber W.N.; Green A.R.;
Lancet 365:1054-1061(2005)
Cited for: VARIANT PV PHE-617;

Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study.
Campbell P.J.; Scott L.M.; Buck G.; Wheatley K.; East C.L.; Marsden J.T.; Duffy A.; Boyd E.M.; Bench A.J.; Scott M.A.; Vassiliou G.S.; Milligan D.W.; Smith S.R.; Erber W.N.; Bareford D.; Wilkins B.S.; Reilly J.T.; Harrison C.N.; Green A.R.;
Lancet 366:1945-1953(2005)
Cited for: VARIANT THCYT3 PHE-617;

A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.
James C.; Ugo V.; Le Couedic J.-P.; Staerk J.; Delhommeau F.; Lacout C.; Garcon L.; Raslova H.; Berger R.; Bennaceur-Griscelli A.; Villeval J.L.; Constantinescu S.N.; Casadevall N.; Vainchenker W.;
Nature 434:1144-1148(2005)
Cited for: VARIANT PV PHE-617; CHARACTERIZATION OF VARIANT PV PHE-617;

A gain-of-function mutation of JAK2 in myeloproliferative disorders.
Kralovics R.; Passamonti F.; Buser A.S.; Teo S.-S.; Tiedt R.; Passweg J.R.; Tichelli A.; Cazzola M.; Skoda R.C.;
N. Engl. J. Med. 352:1779-1790(2005)
Cited for: VARIANT PV PHE-617;

Case records of the Massachusetts General Hospital. Case 15-2006: a 46-year-old woman with sudden onset of abdominal distention.
Chung R.T.; Iafrate A.J.; Amrein P.C.; Sahani D.V.; Misdraji J.;
N. Engl. J. Med. 354:2166-2175(2006)
Cited for: ASSOCIATION OF VARIANT PHE-617 WITH SUSCEPTIBILITY BUDD-CHIARI SYNDROME;

The JAK2 V617F mutation in de novo acute myelogenous leukemias.
Lee J.W.; Kim Y.G.; Soung Y.H.; Han K.J.; Kim S.Y.; Rhim H.S.; Min W.S.; Nam S.W.; Park W.S.; Lee J.Y.; Yoo N.J.; Lee S.H.;
Oncogene 25:1434-1436(2006)
Cited for: VARIANTS AML ASN-607 AND PHE-617;

The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation.
Jamieson C.H.M.; Gotlib J.; Durocher J.A.; Chao M.P.; Mariappan M.R.; Lay M.; Jones C.; Zehnder J.L.; Lilleberg S.L.; Weissman I.L.;
Proc. Natl. Acad. Sci. U.S.A. 103:6224-6229(2006)
Cited for: VARIANT PV PHE-617;

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.