HGD

Protein identityUniProt · HPA

UniProt accession

Q93099

Gene

HGD

Ensembl

ENSG00000113924

Chromosome

3

Canonical length

445 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Golgi apparatus

Quaternary structure

Homohexamer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

445 residues, UniProt reviewed canonical sequence.

>Q93099|HGD
     1  MAELKYISGF GNECSSEDPR CPGSLPEGQN NPQVCPYNLY AEQLSGSAFT CPRSTNKRSW
    61  LYRILPSVSH KPFESIDEGQ VTHNWDEVDP DPNQLRWKPF EIPKASQKKV DFVSGLHTLC
   121  GAGDIKSNNG LAIHIFLCNT SMENRCFYNS DGDFLIVPQK GNLLIYTEFG KMLVQPNEIC
   181  VIQRGMRFSI DVFEETRGYI LEVYGVHFEL PDLGPIGANG LANPRDFLIP IAWYEDRQVP
   241  GGYTVINKYQ GKLFAAKQDV SPFNVVAWHG NYTPYKYNLK NFMVINSVAF DHADPSIFTV
   301  LTAKSVRPGV AIADFVIFPP RWGVADKTFR PPYYHRNCMS EFMGLIRGHY EAKQGGFLPG
   361  GGSLHSTMTP HGPDADCFEK ASKVKLAPER IADGTMAFMF ESSLSLAVTK WGLKASRCLD
   421  ENYHKCWEPL KSHFTPNSRN PAEPN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HGD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

703 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HGD.

Disease | AllUniProt

Conditions HGD is implicated in, by any mechanism.

• Alkaptonuria (AKU) MIM:203500

Disease | GeneticClinVar

272 pathogenic / likely-pathogenic of 633 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Alkaptonuria
• HGD-related disorder
• Clear cell carcinoma of kidney
• See cases
• Nonpapillary renal cell carcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0

gnomAD missense Z

0.29

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• L-phenylalanine catabolic process
• L-tyrosine catabolic process

Molecular functions

• identical protein binding
• metal ion binding
• homogentisate 1,2-dioxygenase activity

Cellular components

• cytosol
• extracellular exosome

Protein domainsUniProt · Pfam · InterPro

• RmlC-like cupin domain superfamily
• RmlC-like jelly roll fold
• Homogentisate 1,2-dioxygenase
• Homogentisate 1,2-dioxygenase, C-terminal domain
• Homogentisate 1,2-dioxygenase, N-terminal domain
• Homogentisate 1,2-dioxygenase C-terminal
• Homogentisate 1,2-dioxygenase N-terminal

KeywordsUniProt

• Acetylation
• Dioxygenase
• Iron
• Metal-binding
• Oxidoreductase
• Phenylalanine catabolism
• Tyrosine catabolism