The IDS gene maps to chromosome Xq28, where it encodes an enzyme of 550 amino acids called iduronate 2-sulfatase (IDS) that belongs to the sulfatase family. This enzyme is localized to the lysosome, and is essential in lysosomal degradation of heparan sulfate and dermatan sulfate.

Defects in the iduronate 2-sulfatase enzyme cause intracellular accumulation of heparan sulfate and dermatan sulfate as well as their excretion in urine. This leads to cell death and to the clinical manifestations of the mucopolysaccharidosis type II disease (MPS II), which is an X-linked lysosomal storage disease. Children with the severe form of this disease have early somatic abnormalities including skeletal deformities, hepatosplenomegaly, and progressive cardiopulmonary deterioration. A prominent feature is neurological damage, which presents as developmental delay and hyperactivity, but progresses to mental retardation and dementia. Affected patients die before 15-years of age, usually as a result of obstructive airway disease or cardiac failure. On the other hand, patients with the mild form survive into adulthood, with attenuated somatic complications and often without mental retardation.

The IDS gene has nine coding exons and spans approximately 57 kb in the genomic DNA. An IDS pseudogene, called IDS2 is located about 80 kb downstream of the transcribed IDS gene. This pseudogene shares homology to exon 2, intron 2, exon 3, intron 3, and intron 7 of the IDS gene. To date about 300 different mutations in the IDS gene have been identified in patients with Hunter syndrome, including gene rearrangements caused by recombination with the IDS2 pseudogene, deletions of certain exons or the entire IDS gene or small mutations including insertions, deletions and point mutations creating a novel splice sites.