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UniProtKB/Swiss-Prot P23769: Variant p.Thr354Met

Endothelial transcription factor GATA-2
Gene: GATA2
Variant information

Variant position:  354
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 Threonine (T) to Methionine (M) at position 354 (T354M, p.Thr354Met).
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 polar (T) to medium size and hydrophobic (M)
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:  Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:21892162}. 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:  Immunodeficiency 21 (IMD21) [MIM:614172]: An immunodeficiency disease characterized by profoundly decreased or absent monocytes, B-lymphocytes, natural killer lymphocytes, and circulating and tissue dendritic cells, with little or no effect on T-cell numbers. Clinical features of DCML include susceptibility to disseminated non-tuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. This syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern. {ECO:0000269|PubMed:21670465}. 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 IMD21 and MDS.
Any additional useful information about the variant.

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



Sequence information

Variant position:  354
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  480
The length of the canonical sequence.

Location on the sequence:   KPKRRLSAARRAGTCCANCQ  T TTTTLWRRNANGDPVCNACG
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                         KPKRRLSAARRAGTCCANCQTTTTTLWRRNANGDPVCNACG

Mouse                         KPKRRLSAARRAGTCCANCQTTTTTLWRRNANGDPVCNACG

Rat                           KPKRRLSAARRAGTCCANCQTTTTTLWRRNANGDPVCNACG

Chicken                       KPKRRLSAARRAGTCCANCQTTTTTLWRRNANGDPVCNACG

Xenopus laevis                KPKRRLSAARRAGTCCANCQTSTTTLWRRNANGDPVCNACG

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 – 480 Endothelial transcription factor GATA-2
Zinc finger 349 – 373 GATA-type 2


Literature citations

Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome.
Hsu A.P.; Sampaio E.P.; Khan J.; Calvo K.R.; Lemieux J.E.; Patel S.Y.; Frucht D.M.; Vinh D.C.; Auth R.D.; Freeman A.F.; Olivier K.N.; Uzel G.; Zerbe C.S.; Spalding C.; Pittaluga S.; Raffeld M.; Kuhns D.B.; Ding L.; Paulson M.L.; Marciano B.E.; Gea-Banacloche J.C.; Orange J.S.; Cuellar-Rodriguez J.; Hickstein D.D.; Holland S.M.;
Blood 118:2653-2655(2011)
Cited for: VARIANTS IMD21 LEU-254; MET-354 AND TRP-398;

Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia.
Hahn C.N.; Chong C.E.; Carmichael C.L.; Wilkins E.J.; Brautigan P.J.; Li X.C.; Babic M.; Lin M.; Carmagnac A.; Lee Y.K.; Kok C.H.; Gagliardi L.; Friend K.L.; Ekert P.G.; Butcher C.M.; Brown A.L.; Lewis I.D.; To L.B.; Timms A.E.; Storek J.; Moore S.; Altree M.; Escher R.; Bardy P.G.; Suthers G.K.; D'Andrea R.J.; Horwitz M.S.; Scott H.S.;
Nat. Genet. 43:1012-1017(2011)
Cited for: VARIANTS MDS MET-354 AND THR-355 DEL;

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.