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# 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.

## In detail

- 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.

## Memory aid

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

## Clinical notes

- 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.

## Related conditions

- [Sickle cell disease](https://durgical.com/en/conditions/sickle-cell-disease/)
- [Thalassemias (α and β)](https://durgical.com/en/conditions/thalassemias/)
- [Methemoglobinemia](https://durgical.com/en/conditions/methemoglobinemia/)
- [Malaria](https://durgical.com/en/conditions/malaria/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)

## Related

- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)
- [Myoglobin](https://durgical.com/en/biochemistry/enzymes/myoglobin/)
- [Heme](https://durgical.com/en/biochemistry/molecules/heme/)
- [Iron metabolism](https://durgical.com/en/biochemistry/topics/iron-metabolism/)

## Test yourself

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.

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

Sources: [Hemoglobin electrophoresis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003639.htm) (MedlinePlus, US National Library of Medicine, 2026); [HBB gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hbb/) (MedlinePlus, US National Library of Medicine, 2026); [Sickle cell disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/sickle-cell-disease/) (MedlinePlus, US National Library of Medicine, 2026); [Beta thalassemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/beta-thalassemia/) (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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