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
  • Homogentisic Acid Oxidase 3 4
  • Homogentisate Oxygenase 3 4
  • Homogentisate Oxidase 2 3
  • Homogentisicase 3 4
  • EC 1.13.11.5 4 52
  • HGO 3 4
  • Homogentisate 1,2-Dioxygenase (Homogentisate Oxidase) 2
  • AKU 3

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 Metabolism and Viral mRNA Translation. Gene Ontology (GO) annotations related to this gene include homogentisate 1,2-dioxygenase activity.

Additional gene information for HGD Gene

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 for HGD Gene

Promoters and enhancers for HGD Gene
GeneHancer (GH) Identifier GH Type GH
Score
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 500.7 +2.0 1955 5.8 EP300 FOXK2 TCF12 POLR2G USF1 NCOR1 TEAD4 KDM6A TCF7 TGIF2 HGD lnc-RABL3-3 ENSG00000242622 RABL3 piR-38423-033
GH03J120641 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 11.1 +39.3 39271 6.2 TCF12 POLR2G TARDBP MYC JUN TAF9B NCOR1 NFRKB NEUROD1 ZNF316 NDUFB4 HGD GTF2E1 RABL3 FSTL1 ENSG00000240661 HSALNG0028402 piR-61365-009
GH03J120791 Enhancer 0.9 Ensembl ENCODE 16.4 -110.7 -110671 4.5 CTCF JUND FOS REST RAD21 TRIM22 TEAD1 SMC3 YY1 FOSL1 HGD STXBP5L RABL3 GTF2E1 HQ292180 NAP1L1P3
GH03J120780 Enhancer 1 Ensembl ENCODE 14.4 -97.6 -97630 4 SP1 JUND FOS EP300 ZNF623 BCL11A TCF12 CBFB POLR2A FOSL2 GTF2E1 HGD RABL3 HQ292180
GH03J120773 Enhancer 0.8 FANTOM5 Ensembl 16.1 -91.5 -91510 2.2 JUND FOS FOSL1 BATF IRF4 ATF2 JUNB IKZF1 TCF7 SMARCE1 GTF2E1 HGD RABL3 HQ292180
- 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 UCSC Golden Path with GeneCards custom track

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

Genomic Locations for HGD Gene
chr3:120,628,168-120,682,571
(GRCh38/hg38)
Size:
54,404 bases
Orientation:
Minus strand
chr3:120,347,015-120,401,418
(GRCh37/hg19)
Size:
54,404 bases
Orientation:
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:
    Q93099-HGD_HUMAN
    Recommended name:
    Homogentisate 1,2-dioxygenase
    Protein Accession:
    Q93099
    Secondary Accessions:
    • A8K417
    • B2R8Z0

    Protein attributes for HGD Gene

    Size:
    445 amino acids
    Molecular mass:
    49964 Da
    Cofactor:
    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

Q93099:
  • VVAWHGN
  • DPSIFTVLT
  • LGPIGANGLA
  • LYAEQLSG
  • AFMFESSLSLAVTKWG
  • MSEFMGLI
  • EICVIQRG
  • DFVIFPPRW
  • PNEICVI
  • TFRPPYYHRNCMSE
  • TMAFMFE

Post-translational modifications for HGD Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

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

Blocks:
  • Homogentisate 1,2-dioxygenase
InterPro:
ProtoNet:

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

Q93099

UniProtKB/Swiss-Prot:

HGD_HUMAN :
  • Belongs to the homogentisate dioxygenase family.
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=1.13.11.5;.
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 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 Model Products

CRISPR Products

miRNA for HGD Gene

miRTarBase miRNAs that target HGD

Inhibitory RNA Products

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

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

Localization for HGD Gene

Subcellular locations from

COMPARTMENTS
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
cytosol 5
nucleus 3
extracellular 2
mitochondrion 2
plasma membrane 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 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: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,IBA 21873635
GO:0006559 L-phenylalanine catabolic process TAS,IEA --
GO:0006570 tyrosine metabolic process IEA --
GO:0006572 tyrosine catabolic process IEA,TAS --
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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
acetic acid Approved Pharma Full agonist, Agonist 141
Bevacizumab Approved, Investigational Pharma VEGF antagonist, Therapeutic Antibodies, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 2327
Vitamin A Approved, Vet_approved Nutra 658
Iron Approved, Experimental Pharma 1496
Oxygen Approved, Vet_approved Pharma 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Homogentisic acid
  • 2,5-Dihydroxyphenylacetic acid
  • 2-(3,6-DIHYDROXYPHENYL)acetIC ACID
  • 2,5-Dihydroxyphenylacetate
  • Homogentisate
  • 2-(3,6-DIHYDROXYPHENYL)acetate
451-13-8
Maleylacetoacetic acid
  • 4-Maleylacetoacetate
  • 4-Maleylacetoacetic acid
  • Maleylacetoacetate
28613-33-4, 5698-52-2
genes like me logo Genes that share compounds with HGD: view

Transcripts for HGD Gene

mRNA/cDNA for HGD Gene

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

CRISPR Products

Inhibitory RNA Products

  • 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: - - - - - - -
SP4:
SP5:
SP6:

Relevant External Links for HGD Gene

GeneLoc Exon Structure for
HGD

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:

Hs.368254

mRNA Expression by UniProt/SwissProt for HGD Gene:

Q93099-HGD_HUMAN
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(2.5)
  • Gall bladder(2.3)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • skull
Thorax:
  • aorta
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
Pelvis:
  • pelvis
  • prostate
  • ureter
  • urethra
  • urinary bladder
Limb:
  • 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
General:
  • 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
chimpanzee
(Pan troglodytes)
Mammalia HGD 31 30
  • 99.78 (n)
OneToOne
cow
(Bos Taurus)
Mammalia HGD 31 30
  • 91.24 (n)
OneToOne
dog
(Canis familiaris)
Mammalia HGD 31 30
  • 91.16 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HGD 31
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hgd 17 31 30
  • 88.44 (n)
rat
(Rattus norvegicus)
Mammalia Hgd 30
  • 88.44 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia HGD 31
  • 76 (a)
OneToOne
chicken
(Gallus gallus)
Aves HGD 31 30
  • 76.92 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HGD 31
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hgd 30
  • 72.95 (n)
Str.8815 30
zebrafish
(Danio rerio)
Actinopterygii hgd 31 30 30
  • 72.54 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta hgo 31 32 30
  • 65.59 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009609 30
  • 61.03 (n)
worm
(Caenorhabditis elegans)
Secernentea hgo-1 31 30
  • 61.83 (n)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons HGO 30
  • 60.27 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.12262 30
rice
(Oryza sativa)
Liliopsida Os06g0103300 30
  • 58.14 (n)
Os.11622 30
wheat
(Triticum aestivum)
Liliopsida Ta.6319 30
barley
(Hordeum vulgare)
Liliopsida Hv.8867 30
corn
(Zea mays)
Liliopsida Zm.8772 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 66 (a)
OneToOne
Cin.14034 30
bread mold
(Neurospora crassa)
Ascomycetes NCU05499 30
  • 55.27 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.14034 30
Species where no ortholog for HGD was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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

ENSEMBL:
Gene Tree for HGD (if available)
TreeFam:
Gene Tree for HGD (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HGD: view image

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
640206 Pathogenic: Alkaptonuria 120,633,257(-) C/G MISSENSE_VARIANT
643931 Pathogenic: Alkaptonuria 120,644,440(-) GCC/G
707988 Likely Benign: not provided 120,638,542(-) G/A MISSENSE_VARIANT
710691 Benign: not provided 120,670,488(-) T/A MISSENSE_VARIANT
712390 Benign: not provided 120,674,948(-) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for HGD Gene

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)
HGD
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HGD

SNP Genotyping and Copy Number Assay Products

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

Disorders for HGD Gene

MalaCards: The human disease database

(18) MalaCards diseases for HGD Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alkaptonuria
  • aku
ochronosis
arthropathy
  • ankylosis of ankle and foot joint
prostate calculus
  • calculus of prostate
idiopathic progressive polyneuropathy
- elite association - COSMIC cancer census association via MalaCards
Search HGD in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HGD_HUMAN
  • 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 mutations affecting the gene represented in this entry.

Additional Disease Information for HGD

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 23 54
  2. Crystal structure of human homogentisate dioxygenase. (PMID: 10876237) Titus GP … Timm DE (Nature structural biology 2000) 3 4 23 54
  3. Allelic heterogeneity of alkaptonuria in Central Europe. (PMID: 10482952) Müller CR … Kress W (European journal of human genetics : EJHG 1999) 3 4 23 54
  4. Mutational analysis of the HGO gene in Finnish alkaptonuria patients. (PMID: 10594001) Beltrán-Valero de Bernabé D … Ranki A (Journal of medical genetics 1999) 3 4 23 54
  5. Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene. (PMID: 10340975) Felbor U … Kress W (The British journal of ophthalmology 1999) 3 4 23 54

Products for HGD Gene

  • Signalway ELISA kits for HGD
  • Signalway Proteins for HGD

Sources for HGD Gene