IthaID: 1052

Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: Variant of Uncertain Significance
Common Name: CD 75 CTG>CGG HGVS Name: HBB:c.227T>G
Hb Name: Hb Pasadena Protein Info: β 75(E19) Leu>Arg

Context nucleotide sequence:

Protein sequence:

Also known as:

Comments: The hydrophobic leucyl residue at β75(E19) is the second residue from the C-terminus of the E helix. It makes neither heme nor interchain contacts, but is part of the interlocking residues that link helices E and A (with Val β11(A8) and Trp β15(A12)). Its substitution by the relatively large, hydrophylic arginyl residue leaves a gap that allows water penetration in the protein interior, loosening the tertiary structure. Also, the arginyl side chain would protrude at the surface so that its guanidium group could be hydrated. The bulky volume of the arginyl residue at βE19 may also disturb the adjacent phenylalanyl residue in the helix at βE15, which ordinarily makes contact with the distal side of the heme in the normal β chain. These changes could account for the instability, increased autoxidation rate and altered oxygen binding properties of Hb Pasadena.

We follow the HGVS sequence variant nomenclature and IUPAC standards.


Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:N/A
Stability: Unstable
Oxygen Affinity: Increased Oxygen Affinity
Associated Phenotypes: N/A


Chromosome: 11
Locus: NG_000007.3
Locus Location: 70951
Size: 1 bp
Located at: β
Specific Location: Exon 2

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: N/A
Ethnic Origin: French
Molecular mechanism: N/A
Inheritance: Recessive
DNA Sequence Determined: No

In silico pathogenicity prediction

Sequence Viewer

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Publications / Origin

  1. Johnson CS, Moyes D, Schroeder WA, Shelton JB, Shelton JR, Beutler E, Hemoglobin Pasadena,alpha 2 beta 275(E19)Leu leads to Arg. Identification by high performance liquid chromatography of a new unstable variant with increased oxygen affinity., Biochimica et biophysica acta, 623(2), 360-7, 1980 PubMed
  2. Shih TB, Jones RT, Johnson CS, Functional properties of Hb Pasadena, alpha 2 beta 2 75(E 19) Leu replaced by Arg., Hemoglobin, 6(2), 153-67, 1982 PubMed
Created on 2010-06-16 16:13:16, Last reviewed on 2023-08-21 10:55:37 (Show full history)

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