IthaID: 691
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 99 AAG>AAT [Lys>Asn] | HGVS Name: | HBA1:c.300G>T |
| Hb Name: | Hb Beziers | Protein Info: | α1 99(G6) Lys>Asn |
Context nucleotide sequence:
TTCGGGTGGACCCGGTCAACTTCAA [G/T] GTGAGCGGCGGGCCGGGAGCGATCT (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFNLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as: Hb Harlow
Comments: The lysine residue at α99(G6) is in the central cavity of the haemoglobin tetramer, situated in the region of the α1β1 contact. The Lys>Asn substitution was reported to bind β globin normally but to disrupt AHSP binding, thus destabilizing α globin. Variant was not associated with any haematological disturbance. Reported in a French Caucasian person during HbA1c screening.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 37996 |
| Size: | 1 bp |
| Located at: | α1 |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | French |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Lacan P, Aubry M, Couprie N, Francina A, Two new alpha chain variants: Hb Die [alpha93(FG5)Val --> Ala (alpha1)] and Hb Beziers [alpha99(G6)Lys --> Asn (alpha1)]., Hemoglobin , 28(1), 59-63, 2004
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013