Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC) !

Hemoglobin changes chains from fetus to adult, and a single amino-acid change is enough to cause diseases such as sickle cell anemia.

Updated 2026-11-01

Key facts

Adult: HbA (α₂β₂) ~97 %, HbA2 (α₂δ₂) 2–3 %, HbF (α₂γ₂) under 1 %.
HbF predominates at birth and binds 2,3-BPG poorly: higher O₂ affinity, useful for taking it from maternal blood. The switch to HbA happens in the first 6 months.
HbS: glutamic acid → valine at position 6 of the β chain; when deoxygenated it polymerises and deforms the red cell (sickle).
HbC: glutamic acid → lysine at the same position; it forms crystals and causes mild hemolysis; HbSC is a moderate form of sickle cell disease.

The α genes (HBA1, HBA2) are on chromosome 16; the β-like genes (ε, γ, δ, β) are on chromosome 11, in the order they are expressed during development.
The valine of HbS creates a hydrophobic patch that fits a pocket of another deoxygenated hemoglobin: long fibres form.
HbF does not join those fibres: that is why hydroxyurea, which raises HbF, eases sickle cell disease.
On alkaline electrophoresis HbA runs fastest toward the anode, then HbF, HbS and HbC (the lysine of HbC adds positive charge).
In β-thalassemia minor HbA2 rises (above 3.5 %); in the major form, HbF does.
In α-thalassemia chains are left over: γ₄ (Hb Bart's) in the fetus and β₄ (HbH) in the adult, both useless for delivering O₂.
HbA1c is HbA with glucose attached non-enzymatically; it reflects mean glycemia over about 3 months. Variants and hemolysis can distort its value.

Electrophoresis, fastest to slowest: «A Fat Santa Claus» (A, F, S, C).

Sickle cell trait (HbAS) usually causes no symptoms and protects against severe P. falciparum malaria; that is why it is commoner where malaria was present.
Newborn screening detects HbS and other variants while HbF still predominates.
Hereditary persistence of HbF is benign and softens sickle cell anemia or thalassemia when inherited together.

Think of the answer, then tap the question to see it.

Which amino-acid change produces HbS?

Glutamic acid replaced by valine at position 6 of the β chain.

Why does HbF have a higher oxygen affinity than HbA?

Its γ chains bind 2,3-BPG poorly, and 2,3-BPG stabilises the low-affinity form.

Which hemoglobin fraction rises in β-thalassemia minor?

HbA2 (α₂δ₂), above 3.5 %.

Why does hydroxyurea improve sickle cell disease?

It raises HbF, which does not join HbS polymers and dilutes HbS inside the red cell.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Hemoglobin electrophoresis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); HBB gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Sickle cell disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Beta thalassemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.