HMBS

The HMBS gene provides instructions for the production of an enzyme called hydroxymethylbilane synthase. Two forms of this enzyme are produced by the HMBS gene. One form is specific to red blood cells (erythrocytes), and the other is present in all tissues, including red blood cells; therefore, red blood cells may make both versions of this enzyme.

Hydroxymethylbilane synthase is responsible for the third step in the production of heme, the iron-containing part of hemoglobin. Hemoglobin is the oxygen-carrying protein in red blood cells. Each step in heme production is controlled by a different enzyme, each of which is produced from a single gene. Hydroxymethylbilane synthase assembles four molecules of porphobilinogen (the product of the second step of the heme manufacturing pathway) to form a compound called hydroxymethylbilane. Five additional enzymes modify this compound before it becomes heme. The heme molecule is incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.

porphyria - caused by mutations in the HMBS gene

More than 200 mutations in the HMBS gene have been identified in people with a form of porphyria known as acute intermittent porphyria. Approximately half of these mutations change one of the building blocks (amino acids) used to make hydroxymethylbilane synthase. Other mutations add or delete small amounts of genetic material within the HMBS gene. As a result of these mutations, reduced amounts of this enzyme are made, which allows byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol, smoking, and dieting), causes acute intermittent porphyria.