HAO1
protein-codinghydroxyacid oxidase 1
Gene summary
This gene is one of three related genes that have 2-hydroxyacid oxidase activity yet differ in encoded protein amino acid sequence, tissue expression and substrate preference. Subcellular location of the encoded protein is the peroxisome. Specifically, this gene is expressed primarily in liver and pancreas and the encoded protein is most active on glycolate, a two-carbon substrate. The protein is also active on 2-hydroxy fatty acids. The transcript detected at high levels in pancreas may represent an alternatively spliced form or the use of a multiple near-consensus upstream polyadenylation site. [provided by RefSeq, Jul 2008]
- GOX1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~57.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HAO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017545.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 1 | 58 | 1 | 60 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 2 | 0 | 59 | 1 | 0 | 62 |
Highest pathogenic variant AF is 0.000021066877
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060015.1 | 8 | MANE Select | |
| Ensembl | ENSP00000368066.3 | 8 | MANE Select | |
| Ensembl | ENSP00000561842.1 | 7 | Standard | |
| Ensembl | ENSP00000653191.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Peroxisome - Homo sapiens (human)
- Glyoxylate and dicarboxylate metabolism - Homo sapiens (human)
- Metabolism of proteins
- Metabolism of amino acids and derivatives
- Metabolism
Biological Process
- fatty acid alpha-oxidation
- protein targeting to peroxisome
- response to oxidative stress
- cellular nitrogen compound metabolic process
- glycolate catabolic process
Molecular Function
- (S)-2-hydroxy-acid oxidase activity
- signaling receptor binding
- glycolate oxidase activity
- FMN binding
- glyoxylate oxidase activity
Cellular Component
- peroxisome
- peroxisomal matrix
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000378789
- Coding exons
- 8
- Length
- 57494
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125740
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.497 | 239 | 218 | 1.09 | 0.0000123 | 2387 |
| Missense (PolyPhen) | 111 | 95.431 | 1.1631 | 990 | ||
| Synonymous | 0.182 | 81 | 83.1 | 0.975 | 0.00000477 | 749 |
| Loss of Function | 1.10 | 13 | 18.0 | 0.720 | 9.14e-7 | 213 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has 2-hydroxyacid oxidase activity. Most active on the 2-carbon substrate glycolate, but is also active on 2-hydroxy fatty acids, with high activity towards 2-hydroxy palmitate and 2- hydroxy octanoate. {ECO:0000269|PubMed:18215067}.;
Recessive Scores
- pRec
- 0.302
Intolerance Scores
- LoFtool
- 0.818
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.950
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |