UniProtKB/SwissProt variant VAR

Variant information

Variant position:

7

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

Type of variant:

LB/B

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Glutamate (E) to Lysine (K) at position 7 (E7K, p.Glu7Lys).

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

Polymorphism:

Genetic variations in HBB are involved in resistance to malaria [MIM:611162]. Hemoglobin S (Hb S), which at homozygosity is responsible for sickle cell anemia, is not associated with any clinical abnormality when heterozygous. At heterozygosity, Hb S confers an increase in protection from life-threatening malaria. Additional variants conferring resistance against severe malaria are hemoglobin C (Hb C) and hemoglobin E (Hb E).

Additional information on the polymorphism described.

Variant description:

In Hb C; confers resistance to severe malaria.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs33930165 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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) valine; in Hb A1c
Glycosylation	9 – 9	N-linked (Glc) (glycation) lysine
Glycosylation	18 – 18	N-linked (Glc) (glycation) lysine
Helix	6 – 17

Literature citations

The beta-globin recombinational hotspot reduces the effects of strong selection around HbC, a recently arisen mutation providing resistance to malaria.
Wood E.T.; Stover D.A.; Slatkin M.; Nachman M.W.; Hammer M.F.;
Am. J. Hum. Genet. 77:637-642(2005)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT LYS-7;

Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S.
Agarwal A.; Guindo A.; Cissoko Y.; Taylor J.G.; Coulibaly D.; Kone A.; Kayentao K.; Djimde A.; Plowe C.V.; Doumbo O.; Wellems T.E.; Diallo D.;
Blood 96:2358-2363(2000)
Cited for: POLYMORPHISM; ASSOCIATION OF VARIANT LYS-7 WITH RESISTANCE TO MALARIA;

Structure of mutant human carbonmonoxyhemoglobin C (betaE6K) at 2.0 A resolution.
Dewan J.C.; Feeling-Taylor A.; Puius Y.A.; Patskovska L.; Patskovsky Y.; Nagel R.L.; Almo S.C.; Hirsch R.E.;
Acta Crystallogr. D 58:2038-2042(2002)
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF VARIANT LYS-7;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P68871: Variant p.Glu7Lys