UniProtKB/Swiss-Prot P68871: Variant p.Glu7Val

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

Variant position:  7
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 Glutamate (E) to Valine (V) at position 7 (E7V, p.Glu7Val).
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 medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Sickle cell anemia (SKCA) [MIM:603903]: Characterized by abnormally shaped red cells resulting in chronic anemia and periodic episodes of pain, serious infections and damage to vital organs. Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular occlusion thus cutting off the blood supply to nearby tissues. {ECO:0000269|PubMed:13464827, ECO:0000269|Ref.10}. 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 SKCA; Hb S; at heterozygosity confers resistance to malaria.
Any additional useful information about the variant.

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



Sequence information

Variant position:  7
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

Location on the sequence:   MVHLTP  E EKSAVTALWGKVNVDEVGGE
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.

TypePositionsDescription
Initiator methionine 1 – 1 Removed
Chain 2 – 147 Hemoglobin subunit beta
Binding site 2 – 2 2,3-bisphosphoglycerate; via amino nitrogen
Binding site 3 – 3 2,3-bisphosphoglycerate
Modified residue 2 – 2 N-acetylvaline
Modified residue 2 – 2 N-pyruvate 2-iminyl-valine; in Hb A1b
Modified residue 10 – 10 Phosphoserine
Modified residue 13 – 13 Phosphothreonine
Glycosylation 2 – 2 N-linked (Glc) (glycation); in Hb A1c
Glycosylation 9 – 9 N-linked (Glc) (glycation)
Glycosylation 18 – 18 N-linked (Glc) (glycation)
Helix 6 – 17


Literature citations

A new hemoglobin, beta chain variant 'Hb S-Wake' confirmed to be on the same chromosome with hemoglobin S mutation, detected in an African-American family.
Kutlar F.; Lallinger R.R.; Holley L.; Glendenning M.; Kutlar A.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT SKCA VAL-7; VARIANT SER-140;

Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin.
Ingram V.M.;
Nature 180:326-328(1957)
Cited for: PROTEIN SEQUENCE OF 3-9; INVOLVEMENT IN SKCA; VARIANT SKCA VAL-7;

How malaria has affected the human genome and what human genetics can teach us about malaria.
Kwiatkowski D.P.;
Am. J. Hum. Genet. 77:171-192(2005)
Cited for: POLYMORPHISM; ASSOCIATION OF VARIANT SKCA VAL-7 WITH RESISTANCE TO MALARIA;

Crystal structure of sickle-cell deoxyhemoglobin at 5 A resolution.
Wishner B.C.; Ward K.B.; Lattman E.E.; Love W.E.;
J. Mol. Biol. 98:179-194(1975)
Cited for: X-RAY CRYSTALLOGRAPHY (5 ANGSTROMS) OF VARIANT SKCA VAL-7;

Structure of fully liganded Hb zeta2beta2s trapped in a tense conformation.
Safo M.K.; Ko T.P.; Abdulmalik O.; He Z.; Wang A.H.; Schreiter E.R.; Russell J.E.;
Acta Crystallogr. D 69:2061-2071(2013)
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF VARIANT SKCA VAL-7 IN COMPLEX WITH HEME AND HBZ; SUBUNIT;

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.