HGD

homogentisate 1,2-dioxygenase

Basic information

Region (hg38): 3:120628172-120682269

Previous symbols: [ "AKU" ]

Links

ENSG00000113924

∙ NCBI:3081 ∙ OMIM:607474 ∙ HGNC:4892 ∙ Uniprot:Q93099 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

alkaptonuria (Strong), mode of inheritance: AR
alkaptonuria (Supportive), mode of inheritance: AR
alkaptonuria (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alkaptonuria	AR	Biochemical; Cardiovascular; Musculoskeletal; Renal	The condition can include cardiac complications, and surveillance for early detection and management of manifestations such as aortic dilatation, valvular disease, or coronary artery calcification may be beneficial; Awareness of complications including urolithiasis and joint degeneration may allow prompt recognition and treatment; Other, more specific therapies are under investigation	Biochemical; Cardiovascular; Musculoskeletal; Renal	12784973; 5472968; 2667832; 2771520; 2270175; 2316305; 8782815; 9154114; 9529363; 9809834; 10482952; 10594001; 11001939; 10970188; 10945668; 12359141; 12501223; 12872815; 15260431; 20301627; 21620748; 21927854; 22482092; 22772574; 23035044; 23357094; 23353776; 23430897; 23430917; 23438536; 23466771; 23486607; 23619548; 23879342; 24009934; 24009959

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HGD gene.

Alkaptonuria (565 variants)
Inborn_genetic_diseases (35 variants)
not_provided (24 variants)
HGD-related_disorder (10 variants)
not_specified (8 variants)
See_cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HGD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000187.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	3 clinvar	2 clinvar	2 clinvar	106 clinvar	1 clinvar	114
missense	90 clinvar	45 clinvar	99 clinvar	8 clinvar	1 clinvar	243
nonsense	16 clinvar	16 clinvar	1 clinvar			33
start loss	2					2
frameshift	34 clinvar	21 clinvar				55
splice donor/acceptor (+/-2bp)	24 clinvar	16 clinvar				40
Total	169	100	102	114	2

Highest pathogenic variant AF is 0.000209401

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HGD	protein_coding	protein_coding	ENST00000283871	14	54399

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.96e-8	0.921	125664	0	82	125746	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.290	223	236	0.947	0.0000125	2948
Missense in Polyphen		99	100.66	0.98353		1220
Synonymous	-1.86	106	84.3	1.26	0.00000463	820
Loss of Function	1.81	16	26.0	0.616	0.00000129	316

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000353	0.000352
Middle Eastern	0.000272	0.000272
South Asian	0.000915	0.000915
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Pathway: Tyrosine metabolism - Homo sapiens (human);Tyrosinemia, transient, of the newborn;Dopamine beta-hydroxylase deficiency;Disulfiram Action Pathway;Phenylalanine and Tyrosine Metabolism;Tyrosine Metabolism;Alkaptonuria;Monoamine oxidase-a deficiency (MAO-A);Hawkinsinuria;Tyrosinemia Type I;Phenylketonuria;Tyrosinemia Type 3 (TYRO3);Tyrosinemia Type 2 (or Richner-Hanhart syndrome);Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Phenylalanine and tyrosine catabolism;Metabolism;tyrosine degradation;Tyrosine metabolism (Consensus)

Recessive Scores

pRec: 0.235

Intolerance Scores

loftool: 0.273
rvis_EVS: -0.38
rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

pHI: 0.591
hipred: N
hipred_score: 0.394
ghis: 0.549

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Hgd
Phenotype: immune system phenotype; renal/urinary system phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: cellular amino acid metabolic process;L-phenylalanine catabolic process;tyrosine catabolic process;oxidation-reduction process
Cellular component: cytosol;extracellular exosome
Molecular function: homogentisate 1,2-dioxygenase activity;protein binding;identical protein binding;metal ion binding