This gene encodes the enzyme homogentisate 1,2 dioxygenase. This enzyme is involved in the catabolism of the amino acids tyrosine and phenylalanine. Mutations in this gene are the cause of the autosomal recessive metabolism disorder alkaptonuria.[provided by RefSeq, May 2010] See more...

Aliases for HGD Gene

Aliases for HGD Gene

  • Homogentisate 1,2-Dioxygenase 2 3 4 5
  • HGO 2 3 4
  • Homogentisic Acid Oxidase 3 4
  • Homogentisate Oxygenase 3 4
  • Homogentisate Oxidase 2 3
  • Homogentisicase 3 4
  • EC 4 50
  • Homogentisate 1,2-Dioxygenase (Homogentisate Oxidase) 2
  • AKU 3
  • HGD 5

External Ids for HGD Gene

Previous HGNC Symbols for HGD Gene

  • AKU

Previous GeneCards Identifiers for HGD Gene

  • GC03M116980
  • GC03M119987
  • GC03M121628
  • GC03M121667
  • GC03M121829
  • GC03P9I0013
  • GC03M120347
  • GC03M117720

Summaries for HGD Gene

Entrez Gene Summary for HGD Gene

  • This gene encodes the enzyme homogentisate 1,2 dioxygenase. This enzyme is involved in the catabolism of the amino acids tyrosine and phenylalanine. Mutations in this gene are the cause of the autosomal recessive metabolism disorder alkaptonuria.[provided by RefSeq, May 2010]

GeneCards Summary for HGD Gene

HGD (Homogentisate 1,2-Dioxygenase) is a Protein Coding gene. Diseases associated with HGD include Alkaptonuria and Ochronosis. Among its related pathways are Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include homogentisate 1,2-dioxygenase activity.

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HGD Gene

Genomics for HGD Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HGD Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J120677 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE 250.7 +1.9 1939 5.8 CEBPA ATF3 POLR2A YY1 MXD4 CEBPB HOMEZ EP300 THAP11 FOXA2 HGD lnc-RABL3-3 RABL3 piR-38423-033 NDUFB4
GH03J120641 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 11.1 +39.3 39255 6.2 NCOR1 ZNF592 BHLHE40 MNT TAF9B ZNF316 RBM22 NFE2 SKIL ATF1 NDUFB4 HGD GTF2E1 RABL3 FSTL1 ENSG00000240661 HSALNG0028402 HSALNG0028400
GH03J120780 Enhancer 0.9 Ensembl ENCODE 14.4 -97.6 -97562 3.8 BCLAF1 SP1 JUND POLR2A BCL11A ZNF592 ZNF623 IRF4 EBF1 CBFB GTF2E1 HGD RABL3 HQ292180 HSALNG0028412 STXBP5L
GH03J120776 Enhancer 0.6 Ensembl 15.9 -91.5 -91546 0.2 JUND IRF4 BATF TCF7 ATF2 JUNB ARID1B SMARCE1 ATF3 CREM HGD RABL3 GTF2E1 HQ292180 HSALNG0028412 STXBP5L
GH03J120719 Enhancer 0.8 ENCODE CraniofacialAtlas 11.1 -37.2 -37182 1.2 ZNF592 ZNF217 ELF1 FOXA2 CTBP1 SIN3A FOXA1 FOXK2 EGR1 NFIB HSALNG0028407 piR-48553-201 HGD lnc-GTF2E1-1 GTF2E1 RABL3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HGD on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HGD

Top Transcription factor binding sites by QIAGEN in the HGD gene promoter:
  • CUTL1
  • FOXI1
  • HFH-3
  • HSF1 (long)
  • HSF1short
  • LUN-1
  • POU2F1
  • POU2F1a
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for HGD Gene

Latest Assembly
54,388 bases
Minus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
54,068 bases
Minus strand

(GRCh37/hg19 by Ensembl)
54,399 bases
Minus strand

Genomic View for HGD Gene

Genes around HGD on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HGD Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HGD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HGD Gene

Proteins for HGD Gene

  • Protein details for HGD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Homogentisate 1,2-dioxygenase
    Protein Accession:
    Secondary Accessions:
    • A8K417
    • B2R8Z0

    Protein attributes for HGD Gene

    445 amino acids
    Molecular mass:
    49964 Da
    Name=Fe cation; Xref=ChEBI:CHEBI:24875;
    Quaternary structure:
    • Homohexamer arranged as a dimer of trimers.

    Three dimensional structures from OCA and Proteopedia for HGD Gene

neXtProt entry for HGD Gene

Selected DME Specific Peptides for HGD Gene


Post-translational modifications for HGD Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibodies for research

  • Abcam antibodies for HGD
  • Santa Cruz Biotechnology (SCBT) Antibodies for HGD

Domains & Families for HGD Gene

Gene Families for HGD Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for HGD Gene

  • Homogentisate 1,2-dioxygenase

Suggested Antigen Peptide Sequences for HGD Gene

GenScript: Design optimal peptide antigens:
  • Homogentisicase (HGD_HUMAN)
  • Homogentisate 1,2-dioxygenase (Homogentisate oxidase) (Q8WW71_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the homogentisate dioxygenase family.
  • Belongs to the homogentisate dioxygenase family.
genes like me logo Genes that share domains with HGD: view

Function for HGD Gene

Molecular function for HGD Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=homogentisate + O2 = 4-maleylacetoacetate + H(+); Xref=Rhea:RHEA:15449, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16169, ChEBI:CHEBI:17105; EC=;.
GENATLAS Biochemistry:
homogentisate 1,2 dioxygenase (49kDa),catalyzing the third step of tyrosine catabolism

Enzyme Numbers (IUBMB) for HGD Gene

Gene Ontology (GO) - Molecular Function for HGD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004411 homogentisate 1,2-dioxygenase activity IEA,IBA 21873635
GO:0005515 protein binding IPI 21044950
GO:0016491 oxidoreductase activity IEA --
GO:0042802 identical protein binding IPI 25416956
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with HGD: view
genes like me logo Genes that share phenotypes with HGD: view

Human Phenotype Ontology for HGD Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HGD Gene

MGI Knock Outs for HGD:
  • Hgd Hgd<tm1a(KOMP)Wtsi>

miRNA for HGD Gene

miRTarBase miRNAs that target HGD

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HGD

No data available for Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for HGD Gene

Localization for HGD Gene

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HGD gene
Compartment Confidence
extracellular 4
cytosol 4
nucleus 3
plasma membrane 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HGD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with HGD: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for HGD Gene

Pathways & Interactions for HGD Gene

genes like me logo Genes that share pathways with HGD: view

UniProtKB/Swiss-Prot Q93099-HGD_HUMAN

  • Pathway: Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 4/6.

Gene Ontology (GO) - Biological Process for HGD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006520 cellular amino acid metabolic process IEA --
GO:0006559 L-phenylalanine catabolic process IEA,TAS --
GO:0006570 tyrosine metabolic process IEA --
GO:0006572 tyrosine catabolic process TAS,IEA --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with HGD: view

No data available for SIGNOR curated interactions for HGD Gene

Drugs & Compounds for HGD Gene

(18) Drugs for HGD Gene - From: ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
acetic acid Approved Pharma 151
Bevacizumab Approved, Investigational Pharma VEGF antagonist, Therapeutic Antibodies, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 2506
Vitamin A Approved, Vet_approved Nutra 747
Oxygen Approved, Vet_approved Pharma 0
Fe2+ Experimental Pharma 0

(3) Additional Compounds for HGD Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Maleylacetoacetic acid
  • 4-Maleylacetoacetate
  • 4-Maleylacetoacetic acid
  • Maleylacetoacetate
  • (2Z)-4,6-Dioxo-2-octenedioic acid
  • Maleylacetoacetic acid
genes like me logo Genes that share compounds with HGD: view

Transcripts for HGD Gene

mRNA/cDNA for HGD Gene

11 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HGD

Alternative Splicing Database (ASD) splice patterns (SP) for HGD Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b ^ 14a · 14b
SP1: - - -
SP2: - - - - -
SP3: - - - - - - -

Relevant External Links for HGD Gene

GeneLoc Exon Structure for

Expression for HGD Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HGD Gene

mRNA differential expression in normal tissues according to GTEx for HGD Gene

This gene is overexpressed in Liver (x31.7) and Kidney - Cortex (x8.5).

Protein differential expression in normal tissues from HIPED for HGD Gene

This gene is overexpressed in Liver, secretome (41.0) and Liver (11.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HGD Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HGD

SOURCE GeneReport for Unigene cluster for HGD Gene:


mRNA Expression by UniProt/SwissProt for HGD Gene:

Tissue specificity: Highest expression in the prostate, small intestine, colon, kidney and liver.

Evidence on tissue expression from TISSUES for HGD Gene

  • Liver(4.7)
  • Kidney(4.6)
  • Blood(4.4)
  • Intestine(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HGD Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeleton
  • urinary
Head and neck:
  • brain
  • ear
  • eye
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • skull
  • aorta
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • kidney
  • pelvis
  • prostate
  • ureter
  • urethra
  • urinary bladder
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
  • blood
  • blood vessel
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with HGD: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for HGD Gene

Orthologs for HGD Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HGD Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HGD 29 30
  • 99.78 (n)
(Bos Taurus)
Mammalia HGD 29 30
  • 91.24 (n)
(Canis familiaris)
Mammalia HGD 29 30
  • 91.16 (n)
(Monodelphis domestica)
Mammalia HGD 30
  • 90 (a)
(Mus musculus)
Mammalia Hgd 29 16 30
  • 88.44 (n)
(Rattus norvegicus)
Mammalia Hgd 29
  • 88.44 (n)
(Ornithorhynchus anatinus)
Mammalia HGD 30
  • 76 (a)
(Gallus gallus)
Aves HGD 29 30
  • 76.92 (n)
(Anolis carolinensis)
Reptilia HGD 30
  • 75 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hgd 29
  • 72.95 (n)
Str.8815 29
(Danio rerio)
Actinopterygii hgd 29 30
  • 72.54 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta hgo 29 30 31
  • 65.59 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009609 29
  • 61.03 (n)
(Caenorhabditis elegans)
Secernentea hgo-1 29 30
  • 61.83 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons HGO 29
  • 60.27 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.12262 29
(Oryza sativa)
Liliopsida Os06g0103300 29
  • 58.14 (n)
Os.11622 29
(Hordeum vulgare)
Liliopsida Hv.8867 29
(Triticum aestivum)
Liliopsida Ta.6319 29
(Zea mays)
Liliopsida Zm.8772 29
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 66 (a)
Bread mold
(Neurospora crassa)
Ascomycetes NCU05499 29
  • 55.27 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.14034 29
Species where no ortholog for HGD was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for HGD Gene

Gene Tree for HGD (if available)
Gene Tree for HGD (if available)
Evolutionary constrained regions (ECRs) for HGD: view image
Alliance of Genome Resources:
Additional Orthologs for HGD

Paralogs for HGD Gene

No data available for Paralogs for HGD Gene

Variants for HGD Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HGD Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
1032245 Pathogenic: Alkaptonuria 120,644,308(-) TTTTAC/T
836287 Likely Pathogenic: Alkaptonuria 120,644,413(-) A/G
NM_000187.4(HGD):c.680T>C (p.Phe227Ser)
850435 Pathogenic: Alkaptonuria 120,633,296(-) G/A
NM_000187.4(HGD):c.1039C>T (p.Arg347Ter)
855743 Pathogenic: Alkaptonuria 120,652,643(-) C/T
NM_000187.4(HGD):c.291G>A (p.Trp97Ter)
861290 Conflicting Interpretations: Alkaptonuria 120,633,221(-) C/T
NM_000187.4(HGD):c.1114G>A (p.Gly372Arg)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HGD Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HGD Gene

Variant ID Type Subtype PubMed ID
nsv829699 CNV loss 17160897

Variation tolerance for HGD Gene

Residual Variation Intolerance Score: 21.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.13; 51.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HGD Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HGD Gene

Disorders for HGD Gene

MalaCards: The human disease database

(15) MalaCards diseases for HGD Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
  • aku
  • ankylosis of ankle and foot joint
aortic valve disease 2
  • aovd2
  • pntsu
- elite association - COSMIC cancer census association via MalaCards
Search HGD in MalaCards View complete list of genes associated with diseases


  • Alkaptonuria (AKU) [MIM:203500]: An autosomal recessive error of metabolism characterized by an increase in the level of homogentisic acid. The clinical manifestations are urine that turns dark on standing and alkalinization, black ochronotic pigmentation of cartilage and collagenous tissues, and spine arthritis. {ECO:0000269 PubMed:10205262, ECO:0000269 PubMed:10340975, ECO:0000269 PubMed:10482952, ECO:0000269 PubMed:10594001, ECO:0000269 PubMed:19862842, ECO:0000269 PubMed:21437689, ECO:0000269 PubMed:23353776, ECO:0000269 PubMed:23430897, ECO:0000269 PubMed:25681086, ECO:0000269 PubMed:8782815, ECO:0000269 PubMed:9154114, ECO:0000269 PubMed:9529363, ECO:0000269 PubMed:9630082}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for HGD

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HGD: view

No data available for Genatlas for HGD Gene

Publications for HGD Gene

  1. Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria. (PMID: 19862842) Vilboux T … Gahl WA (Human mutation 2009) 3 4 22 72
  2. Allelic heterogeneity of alkaptonuria in Central Europe. (PMID: 10482952) Müller CR … Kress W (European journal of human genetics : EJHG 1999) 3 4 22 72
  3. The molecular basis of alkaptonuria. (PMID: 8782815) Fernández-Cañón JM … Rodríguez de Córdoba S (Nature genetics 1996) 3 4 22 72
  4. Crystal structure of human homogentisate dioxygenase. (PMID: 10876237) Titus GP … Timm DE (Nature structural biology 2000) 3 4 22
  5. Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene (HGO). (PMID: 10205262) Beltrán-Valero de Bernabé D … Rodríguez de Córdoba S (American journal of human genetics 1999) 3 4 22

Products for HGD Gene

Sources for HGD Gene