UniProtKB/Swiss-Prot P68871: Variant p.Glu27Lys

Hemoglobin subunit beta
Gene: HBB
Chromosomal location: 11p15.5
Variant information

Variant position:  27
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 27 (E27K, p.Glu27Lys).
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:  Beta-thalassemia (B-THAL) [MIM:613985]: A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of detectable beta globin causes beta(+)-thalassemia. In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate severity), and thalassemia minor that is asymptomatic. {ECO:0000269|PubMed:12144064, ECO:0000269|PubMed:12149194, ECO:0000269|PubMed:15481886, ECO:0000269|PubMed:2399911, ECO:0000269|PubMed:6166632, ECO:0000269|PubMed:7693620}. 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 B-THAL; Hb E; confers resistance to severe malaria.
Any additional useful information about the variant.

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

Sequence information

Variant position:  27
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  147
The length of the canonical sequence.

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.

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.

Chain 2 – 147 Hemoglobin subunit beta
Modified residue 10 – 10 Phosphoserine
Modified residue 13 – 13 Phosphothreonine
Modified residue 45 – 45 Phosphoserine
Glycosylation 9 – 9 N-linked (Glc) (glycation) lysine
Glycosylation 18 – 18 N-linked (Glc) (glycation) lysine
Helix 21 – 35

Literature citations

Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha 2 beta2(26)Glu leads to Lys).
Benz E.J. Jr.; Berman B.W.; Tonkonow B.L.; Coupal E.; Coates T.; Boxer L.A.; Altman A.; Adams J.G. III;
J. Clin. Invest. 68:118-126(1981)

Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria.
Chotivanich K.; Udomsangpetch R.; Pattanapanyasat K.; Chierakul W.; Simpson J.; Looareesuwan S.; White N.;
Blood 100:1172-1176(2002)

Double heterozygosity for Hb Pyrgos [beta83(EF7)Gly-->Asp] and Hb E [beta26(B8)Glu-->Lys] found in association with alpha-thalassemia.
Sawangareetrakul P.; Svasti S.; Yodsowon B.; Winichagoon P.; Srisomsap C.; Svasti J.; Fucharoen S.;
Hemoglobin 26:191-196(2002)

The 'hot-spot' of Hb E [beta26(B8)Glu-->Lys] in Southeast Asia: beta-globin anomalies in the Lao Theung population of southern Laos.
Flatz G.; Sanguansermsri T.; Sengchanh S.; Horst D.; Horst J.;
Hemoglobin 28:197-204(2004)
Cited for: VARIANT B-THAL LYS-27;

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.