HGD (originally HGO) is the alkaptonuria gene; alkaptonuria results from loss of homogentisate 1,2-dioxygenase activity, causing accumulation of homogentisic acid, an intermediary product of tyrosine and phenylalanine catabolism.

Homogentisic acid, the substrate of HGD, is an intermediate of phenylalanine and tyrosine degradation; the aromatic ring is opened and oxidized by the hexameric homogentisate 1,2-dioxygenase, and reduced HGD catalytic activity causes HGA accumulation in alkaptonuria.

X-ray structure of human HGD reveals a homohexamer (dimer of trimers) with one catalytic Fe ion per subunit at the active site.

High-throughput protein-complementation screen for telomere-signaling regulators reported an HGD-TERF1 interaction; a bulk-screen hit rather than a functional partner of HGD's catalytic role.

Systematic binary protein-protein interaction mapping recorded an HGD self (identical-protein) interaction, consistent with its known homo-oligomer.

HuRI binary interactome map recorded HGD self-interaction (identical protein binding) and an HGD-NTAQ1 interaction.

HGD peptides were detected by bulk proteomics of prostatic-secretion-derived urinary exosomes; a mass-spectrometry co-purification, not evidence of functional exosomal localization.

HGD was identified among proteins in a large-scale proteomic survey of urinary exosomes.

Cytosolic homogentisate 1,2-dioxygenase catalyzes the reaction of homogentisate and molecular oxygen to form 4-maleylacetoacetate; HGD is a homohexamer with one Fe(2+) ion per monomer as catalytic cofactor.