The HGD gene provides instructions for making an enzyme called homogentisate 1,2-dioxygenase, which is active mainly in the liver and kidneys. This enzyme participates in a multi step process that breaks down two protein building blocks (amino acids), phenylalanine and tyrosine. They get broken down when they are no longer needed or when there are too many of them. These two amino acids also play a role in making certain brain chemicals (neurotransmitters), hormones, and pigments.

Homogentisate 1,2-dioxygenase is responsible for a specific step in the breakdown of phenylalanine and tyrosine. Previous steps convert the two amino acids into a molecule called homogentisic acid. Homogentisate 1,2-dioxygenase adds two oxygen atoms to homogentisic acid, converting it to another molecule called maleylacetoacetate. Other enzymes break down maleylacetoacetate into smaller molecules that are later used for energy or to make other products that can be used by the body.

Tests Listed in the Genetic Testing Registry

• Tests of HGD

Scientific Articles on PubMed

• PubMed

Catalog of Genes and Diseases from OMIM

• HOMOGENTISATE 1,2-DIOXYGENASE; HGD

Gene and Variant Databases

• NCBI Gene
• ClinVar

• Amaya AA, Brzezinski KT, Farrington N, Moran GR. Kinetic analysis of human homogentisate 1,2-dioxygenase. Arch Biochem Biophys. 2004 Jan 1;421(1):135-42. doi: 10.1016/j.abb.2003.10.014. Citation on PubMed
• Bernardini G, Braconi D, Zatkova A, Sireau N, Kujawa MJ, Introne WJ, Spiga O, Geminiani M, Gallagher JA, Ranganath LR, Santucci A. Alkaptonuria. Nat Rev Dis Primers. 2024 Mar 7;10(1):16. doi: 10.1038/s41572-024-00498-x. Citation on PubMed
• Goicoechea De Jorge E, Lorda I, Gallardo ME, Perez B, Perez De Ferran C, Mendoza H, Rodriguez De Cordoba S. Alkaptonuria in the Dominican Republic: identification of the founder AKU mutation and further evidence of mutation hot spots in the HGO gene. J Med Genet. 2002 Jul;39(7):E40. doi: 10.1136/jmg.39.7.e40. No abstract available. Citation on PubMed or Free article on PubMed Central
• Introne WJ, Perry M, Chen M. Alkaptonuria. 2003 May 9 [updated 2021 Jun 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1454/ Citation on PubMed
• Rodriguez JM, Timm DE, Titus GP, Beltran-Valero De Bernabe D, Criado O, Mueller HA, Rodriguez De Cordoba S, Penalva MA. Structural and functional analysis of mutations in alkaptonuria. Hum Mol Genet. 2000 Sep 22;9(15):2341-50. doi: 10.1093/oxfordjournals.hmg.a018927. Citation on PubMed
• Srsen S, Muller CR, Fregin A, Srsnova K. Alkaptonuria in Slovakia: thirty-two years of research on phenotype and genotype. Mol Genet Metab. 2002 Apr;75(4):353-9. doi: 10.1016/S1096-7192(02)00002-1. Citation on PubMed
• Zatkova A, Chmelikova A, Polakova H, Ferakova E, Kadasi L. Rapid detection methods for five HGO gene mutations causing alkaptonuria. Clin Genet. 2003 Feb;63(2):145-9. doi: 10.1034/j.1399-0004.2003.00027.x. Citation on PubMed