It carries off some of the body's respiratory carbon dioxide (about 20–25% of the total)[7] as carbaminohemoglobin, in which CO2 binds to the heme protein.

The majority of hemoglobin variants do not cause disease and are most commonly discovered either incidentally or through newborn screening.

Hb variants can usually be detected by protein-based assay methods such as electrophoresis,[15] isoelectric focusing,[16] or high-performance liquid chromatography.

[18] The hemoglobin structural variants can be broadly classified as follows:[19] Methemoglobinemia is a condition caused by elevated levels of methemoglobin in the blood.

[23][24] Methemoglobinemia can be hereditary but more commonly occurs as a side effect of certain medications or by abuse of recreational drugs.

The excess chains that fail to incorporate into normal hemoglobin can form non-functional aggregates that precipitate.

In this, excess beta-globin forms β4-tetramers, which accumulate and precipitate in red blood cells, damaging their membranes.

Anemia in beta thalassemia results from a combination of ineffective production of RBCs, peripheral hemolysis, and an overall reduction in hemoglobin synthesis.

Malaria parasites infect red blood cells, but subtly disturb normal cellular function and subvert the immune response.

A number of mechanisms have been proposed to explain the increased chance of survival for the carrier of an abnormal hemoglobin trait.