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The official name of this gene is “hemoglobin, beta.”
HBB is the gene's official symbol. The HBB gene is also known by other names, listed below.
The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of a larger protein called hemoglobin, which is located inside red blood cells. Hemoglobin normally consists of four protein subunits: two subunits of beta-globin and two subunits of another protein called alpha-globin.
Each of the four protein subunits of hemoglobin carries an iron-containing molecule called heme. Heme molecules are necessary for red blood cells to pick up oxygen in the lungs and deliver it to cells throughout the body. A complete hemoglobin protein is capable of carrying four oxygen molecules at a time (one attached to each heme molecule). Oxygen attached to hemoglobin gives blood its bright red color.
More than 250 mutations in the HBB gene have been found to cause beta thalassemia. Most of the mutations involve a change in a single DNA building block (nucleotide) within or near the HBB gene. Other mutations insert or delete a small number of nucleotides in the HBB gene.
HBB gene mutations that decrease beta-globin production result in a type of the condition called beta-plus (B+) thalassemia. Mutations that prevent cells from producing any beta-globin result in beta-zero (B0) thalassemia.
Without proper amounts of beta-globin, sufficient hemoglobin cannot be formed. A lack of hemoglobin disrupts the normal development of red blood cells. A shortage of mature red blood cells prevents these cells from carrying and delivering enough oxygen to satisfy the body's energy needs. A lack of oxygen in the body's tissues can lead to poor growth, organ damage, and other health problems associated with beta thalassemia.
Mutations in specific regions of the HBB gene cause red blood cells to produce an abnormal form of hemoglobin called hemoglobin M. This form of hemoglobin disrupts the protein's interaction with iron and interferes with the delivery of oxygen to cells. As a result, people with this condition may have a bluish tint to their skin, mucous membranes (such as the moist lining of the nose and mouth), and underneath their fingernails.
Sickle cell anemia, a common form of sickle cell disease, is caused by a particular mutation in the HBB gene. This mutation results in the production of an abnormal version of beta-globin called hemoglobin S or HbS. In this condition, hemoglobin S replaces both beta-globin subunits in hemoglobin. The mutation changes a single protein building block (amino acid) in beta-globin. Specifically, the amino acid glutamic acid is replaced with the amino acid valine at position 6 in beta-globin, written as Glu6Val or E6V. Replacing glutamic acid with valine causes the abnormal HbS subunits to stick together and form long, rigid molecules. The rigid HbS molecules bend red blood cells into a sickle (crescent) shape. The sickle-shaped cells die prematurely, which can lead to a shortage of red blood cells (anemia). The sickle-shaped cells can also block small blood vessels, causing pain and organ damage.
Mutations in the HBB gene can also cause other abnormalities in beta-globin, leading to other types of sickle cell disease. These abnormal forms of beta-globin are often designated by letters of the alphabet or sometimes by a name. In these other types of sickle cell disease, just one beta-globin subunit is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C or hemoglobin E.
In hemoglobin SC (HbSC) disease, the beta-globin subunits are replaced by hemoglobin S and hemoglobin C. Hemoglobin C results when the amino acid lysine replaces the amino acid glutamic acid at position 6 in beta-globin (written Glu6Lys or E6K). The severity of hemoglobin SC disease is quite variable, but it can be as severe as sickle cell anemia. Hemoglobin E (HbE) is caused when the amino acid glutamic acid is replaced with the amino acid lysine at position 26 in beta-globin (written Glu26Lys or E26K). In some cases, the hemoglobin E mutation is present with hemoglobin S. In these cases, a person may have more severe signs and symptoms associated with sickle cell anemia, such as episodes of pain, anemia, and abnormal spleen function.
Other conditions, known as hemoglobin sickle-beta thalassemias (HbSBetaThal), are caused when mutations that produce hemoglobin S and beta thalassemia occur together. The signs and symptoms of hemoglobin S-beta thalassemias are usually more severe than those of hemoglobin SC disease, and may include severe pain and organ damage.
Hundreds of variations have been identified in the HBB gene. These changes result in the production of different versions of beta-globin. Some of these variations cause no noticeable signs or symptoms, while others may affect a person's health. Two of the most common variants are hemoglobin C and hemoglobin E.
Hemoglobin C (HbC), caused by the Glu6Lys mutation in beta-globin, is more common in people of West African descent than in other populations. People who have two hemoglobin C subunits in their hemoglobin, instead of normal beta-globin, have a mild condition called hemoglobin C disease. This condition often causes chronic anemia, in which the red blood cells are broken down prematurely.
Hemoglobin E (HbE), caused by the Glu26Lys mutation in beta-globin, is a variant of hemoglobin most commonly found in the Southeast Asian population. When a person has two hemoglobin E subunits in their hemoglobin in place of beta-globin, a mild anemia called hemoglobin E disease can occur. In some cases, the mutations that produce hemoglobin E and beta thalassemia are found together. People with this hemoglobin combination can have signs and symptoms ranging from mild anemia to severe thalassemia major.
Cytogenetic Location: 11p15.5
Molecular Location on chromosome 11: base pairs 5,246,695 to 5,248,300
The HBB gene is located on the short (p) arm of chromosome 11 at position 15.5.
More precisely, the HBB gene is located from base pair 5,246,695 to base pair 5,248,300 on chromosome 11.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about HBB helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
amino acid ; anemia ; cell ; chronic ; DNA ; gene ; Hb ; heme ; hemoglobin ; hemoglobin M ; iron ; locus ; molecule ; mucous ; mutation ; newborn screening ; nucleotide ; oxygen ; population ; protein ; screening ; subunit ; thalassemia
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.