id: Q9UJM8
gene_symbol: HAO1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: HAO1 (hydroxyacid oxidase 1; also called glycolate oxidase, GO/GOX, or
  glyoxylate oxidase; HAOX1) is a peroxisomal FMN-dependent (S)-2-hydroxy-acid oxidase
  of the FMN-dependent alpha-hydroxy acid dehydrogenase family. It is a homotetramer
  localized to the peroxisomal matrix and is highly expressed in liver. HAO1 has broad
  substrate specificity but preferentially oxidizes glycolate to glyoxylate, using
  molecular O2 as the physiological electron acceptor and generating hydrogen peroxide
  (H2O2); it also oxidizes long-chain 2-hydroxy fatty acids (e.g. 2-hydroxyhexadecanoate,
  2-hydroxyoctanoate) with lower efficiency, contributing to fatty-acid alpha-oxidation.
  Because it produces glyoxylate, the immediate precursor of oxalate, HAO1 is central
  to hepatic oxalate production, and in primary hyperoxaluria glyoxylate that is not
  detoxified to glycine is converted to oxalate, causing kidney stones and systemic
  oxalosis. HAO1 is therefore a validated therapeutic target, and the siRNA drug lumasiran
  silences hepatic HAO1 to lower oxalate in primary hyperoxaluria.
existing_annotations:
- term:
    id: GO:0003973
    label: (S)-2-hydroxy-acid oxidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Core molecular function of HAO1. This IEA (RHEA:16789 / EC:1.1.3.15)
      captures the FMN-dependent (S)-2-hydroxy-acid oxidase activity that preferentially
      oxidizes glycolate to glyoxylate, matching the experimentally determined function.
    action: ACCEPT
    reason: This is the correct, specific core molecular function and is independently
      supported by direct experimental IDA annotations (PMID:10777549, PMID:18215067)
      and by the UniProt catalytic activity records (RHEA:16789, EC 1.1.3.15).
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: Broad substrate specificity (S)-2-hydroxy-acid oxidase that
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: preferentially oxidizes glycolate
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: HAO1 is a soluble peroxisomal matrix enzyme with a C-terminal PTS1 microbody
      targeting signal. This IEA correctly places it in the peroxisomal matrix.
    action: ACCEPT
    reason: Consistent with the experimental IDA localization (PMID:10777549) and
      the UniProt subcellular location; HAO1 carries a C-terminal microbody targeting
      signal.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0010181
    label: FMN binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: HAO1 is an FMN-dependent flavoenzyme; FMN is the catalytic cofactor.
      This InterPro-based IEA is correct but represents a supporting cofactor-binding
      function rather than the core catalytic function.
    action: ACCEPT
    reason: FMN is the experimentally confirmed cofactor (PMID:17669354, PMID:18215067);
      multiple FMN-binding residues are annotated in UniProt. Correct but secondary
      to the oxidase activity.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: Name=FMN;
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: Belongs to the FMN-dependent alpha-hydroxy acid
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Generic parent term for the oxidase activity. Not wrong, but far less
      informative than the specific (S)-2-hydroxy-acid oxidase activity that is separately
      annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0016491 is a high-level ancestor of the specific GO:0003973 activity
      already annotated with experimental evidence; it adds no information beyond the
      more specific term.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: Broad substrate specificity (S)-2-hydroxy-acid oxidase that
- term:
    id: GO:0019395
    label: fatty acid oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning inference. HAO1 does oxidize long-chain 2-hydroxy
      fatty acids, but its role is in fatty-acid alpha-oxidation (the specific IDA
      annotation GO:0001561), not in general fatty acid oxidation (which connotes beta-oxidation-type
      degradation).
    action: MARK_AS_OVER_ANNOTATED
    reason: The enzyme's fatty-acid-related role is the more specific alpha-oxidation
      of 2-hydroxy fatty acids (separately annotated as GO:0001561 with IDA). The broad
      ARBA-derived "fatty acid oxidation" term is imprecise for this activity.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: long chain hydroxyacids such
    - reference_id: PMID:10777549
      supporting_text: substrate, glycolate, but is also active on 2-hydroxy fatty
        acids
- term:
    id: GO:0047639
    label: alcohol oxidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: RHEA-based IEA (RHEA:25311, glycolate + O2 = glyoxylate + H2O2). Although
      glycolate has a hydroxyl group, the informative and correct molecular function
      term for this reaction is the (S)-2-hydroxy-acid oxidase activity (GO:0003973),
      not the generic "alcohol oxidase activity".
    action: MARK_AS_OVER_ANNOTATED
    reason: The Rhea-to-GO mapping assigns a less-specific, potentially misleading
      MF term; the glycolate oxidation reaction is properly captured by the (S)-2-hydroxy-acid
      oxidase activity already annotated with experimental evidence.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: preferentially oxidizes glycolate
- term:
    id: GO:0047969
    label: glyoxylate oxidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Oxidation of glyoxylate to oxalate (EC 1.2.3.5). HAO1 can catalyze this
      reaction in vitro, but it is a low-efficiency secondary activity that is "most
      likely not relevant under normal conditions"; the primary reaction is glycolate
      to glyoxylate.
    action: KEEP_AS_NON_CORE
    reason: A genuine but physiologically minor in vitro activity (kcat/KM far below
      that for glycolate). Retained but marked non-core because glycolate oxidation,
      not glyoxylate oxidation, is the primary physiological function.
    supported_by:
    - reference_id: PMID:18215067
      supporting_text: oxidation of glycolate to glyoxylate is the primary reaction
        catalyzed by GO, while the oxidation of glyoxylate to oxalate is most likely
        not relevant under normal conditions
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: HAO1 is a peroxisomal enzyme. This IEA (parent of the more specific peroxisomal
      matrix term) correctly places HAO1 in the peroxisome.
    action: ACCEPT
    reason: Correct organelle localization, consistent with the experimental IDA to
      the peroxisomal matrix (PMID:10777549) and the UniProt subcellular location.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ensembl ortholog-transfer inference. HAO1 is a producer of H2O2 (a reactive
      oxygen species) rather than a component of the cellular response to oxidative
      stress; there is no direct evidence that HAO1 participates in defending against
      oxidative stress.
    action: MARK_AS_OVER_ANNOTATED
    reason: The activity generates H2O2 as a by-product; casting HAO1 as part of the
      "response to oxidative stress" over-interprets an electronic ortholog transfer
      and does not reflect a validated protective role.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: leading to the production of H2O2
- term:
    id: GO:0006545
    label: glycine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: UniPathway mapping (UPA00288). The glyoxylate produced by HAO1 is transaminated
      by alanine-glyoxylate aminotransferase to form glycine, so HAO1 provides an upstream
      substrate for peroxisomal glycine synthesis rather than performing a glycine-synthetic
      step itself.
    action: KEEP_AS_NON_CORE
    reason: HAO1 contributes the glyoxylate substrate for glycine biosynthesis (a genuine
      upstream role recorded in the UniProt pathway annotation) but does not itself
      catalyze glycine formation; retained as a non-core, contributory process.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'Amino-acid biosynthesis; glycine biosynthesis'
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: IDA
  original_reference_id: PMID:10777549
  qualifier: located_in
  review:
    summary: Direct experimental demonstration that HAO1 (HAOX1) is targeted to peroxisomes;
      it is a soluble matrix enzyme. This is the primary evidence for the peroxisomal
      matrix localization.
    action: ACCEPT
    reason: Experimental IDA localization of the human enzyme to peroxisomes, consistent
      with the UniProt subcellular location and the presence of a C-terminal PTS1 signal.
    supported_by:
    - reference_id: PMID:10777549
      supporting_text: targeted to peroxisomes and have 2-hydroxy acid
- term:
    id: GO:0047969
    label: glyoxylate oxidase activity
  evidence_type: IDA
  original_reference_id: PMID:10777549
  qualifier: enables
  review:
    summary: Experimental demonstration that HAOX1 can oxidize glyoxylate to oxalate.
      This is a genuine but physiologically minor activity relative to the primary
      glycolate oxidation.
    action: KEEP_AS_NON_CORE
    reason: A real, experimentally supported in vitro activity implicated in oxalate
      production (and PH1 pathophysiology), but a low-efficiency side reaction rather
      than the core physiological function. Retained as non-core.
    supported_by:
    - reference_id: PMID:10777549
      supporting_text: implicate HAOX1 as a mediator of PH1 pathophysiology
- term:
    id: GO:0047969
    label: glyoxylate oxidase activity
  evidence_type: IDA
  original_reference_id: PMID:17669354
  qualifier: enables
  review:
    summary: Characterization of recombinant human liver glycolate oxidase confirming
      it can contribute to oxalate production. As above, glyoxylate-to-oxalate oxidation
      is a minor secondary activity relative to glycolate oxidation.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported minor activity; the same physiologically-minor
      glyoxylate oxidase reaction. Retained as non-core, deferring to the curator's
      experimental annotation.
    supported_by:
    - reference_id: PMID:17669354
      supporting_text: to the production of oxalate with formation of kidney stones
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  qualifier: located_in
  review:
    summary: This Reactome annotation reflects the transient cytosolic pool of HAO1
      cargo prior to PTS1-dependent peroxisomal import (the "Cargo of PEX5S,L translocates
      from the cytosol to the peroxisomal matrix" reaction), not the steady-state functional
      location.
    action: MARK_AS_OVER_ANNOTATED
    reason: HAO1 is synthesized in the cytosol and imported into peroxisomes; the cytosolic
      annotation captures a transit state of the peroxisomal import pathway rather
      than a distinct cytosolic function. The functional location is the peroxisomal
      matrix.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033236
  qualifier: located_in
  review:
    summary: As above, this Reactome cytosol annotation derives from the peroxisomal
      protein import pathway (PEX5:cargo docking), representing an import-transit state
      rather than a steady-state cytosolic localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Reflects the cytosolic phase of PTS1-mediated peroxisomal import, not an
      independent cytosolic function; the mature enzyme resides in the peroxisomal
      matrix.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389842
  qualifier: located_in
  review:
    summary: Reactome-curated peroxisomal matrix localization ("HAO1 tetramer oxidizes
      glycolate to glyoxylate"), consistent with the experimental and UniProt evidence.
    action: ACCEPT
    reason: Correct steady-state functional location, agreeing with the IDA (PMID:10777549)
      and UniProt subcellular location.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389862
  qualifier: located_in
  review:
    summary: Reactome-curated peroxisomal matrix localization associated with the "Conversion
      of glyoxylate to oxalate" reaction. Correct localization.
    action: ACCEPT
    reason: Correct peroxisomal matrix localization, consistent with experimental and
      UniProt evidence.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  qualifier: located_in
  review:
    summary: Reactome peroxisomal matrix localization (peroxisomal import pathway).
      Consistent with the mature functional location of HAO1.
    action: ACCEPT
    reason: Correct peroxisomal matrix localization; the destination of the PTS1-mediated
      import pathway.
    supported_by:
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Peroxisome matrix'
- term:
    id: GO:0003973
    label: (S)-2-hydroxy-acid oxidase activity
  evidence_type: IDA
  original_reference_id: PMID:10777549
  qualifier: enables
  review:
    summary: Direct experimental demonstration that HAOX1 has 2-hydroxy acid oxidase
      activity and is most active on glycolate. This is the core molecular function
      of HAO1.
    action: ACCEPT
    reason: Primary experimental evidence for the core (S)-2-hydroxy-acid oxidase activity,
      with glycolate as the preferred substrate.
    supported_by:
    - reference_id: PMID:10777549
      supporting_text: targeted to peroxisomes and have 2-hydroxy acid
    - reference_id: PMID:10777549
      supporting_text: substrate, glycolate, but is also active on 2-hydroxy fatty
        acids
- term:
    id: GO:0001561
    label: fatty acid alpha-oxidation
  evidence_type: IDA
  original_reference_id: PMID:18215067
  qualifier: involved_in
  review:
    summary: HAO1 oxidizes long-chain 2-hydroxy fatty acids (e.g. 2-hydroxyoctanoate,
      2-hydroxyhexadecanoate), a step within the fatty-acid alpha-oxidation pathway.
      This is a genuine but secondary role relative to glycolate oxidation.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported involvement in alpha-oxidation via oxidation of
      2-hydroxy fatty acids, but performed with much lower catalytic efficiency than
      glycolate oxidation; retained as a non-core biological process.
    supported_by:
    - reference_id: PMID:10777549
      supporting_text: substrate, glycolate, but is also active on 2-hydroxy fatty
        acids
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: long chain hydroxyacids such
- term:
    id: GO:0003973
    label: (S)-2-hydroxy-acid oxidase activity
  evidence_type: IDA
  original_reference_id: PMID:18215067
  qualifier: enables
  review:
    summary: Structural and kinetic study confirming the FMN-dependent (S)-2-hydroxy-acid
      oxidase activity, with glycolate oxidation to glyoxylate as the primary reaction.
      Core molecular function.
    action: ACCEPT
    reason: Direct experimental (structural/kinetic) support for the core (S)-2-hydroxy-acid
      oxidase activity; the study explicitly identifies glycolate-to-glyoxylate as
      the primary catalyzed reaction.
    supported_by:
    - reference_id: PMID:18215067
      supporting_text: catalyzes the FMN-dependent oxidation of glycolate to glyoxylate
        and glyoxylate to oxalate
    - reference_id: PMID:18215067
      supporting_text: oxidation of glycolate to glyoxylate is the primary reaction
        catalyzed by GO, while the oxidation of glyoxylate to oxalate is most likely
        not relevant under normal conditions
- term:
    id: GO:0010181
    label: FMN binding
  evidence_type: IDA
  original_reference_id: PMID:18215067
  qualifier: enables
  review:
    summary: Crystal structures of HAO1 in complex with FMN directly demonstrate FMN
      binding. FMN is the catalytic cofactor of this flavoenzyme.
    action: ACCEPT
    reason: Direct structural evidence (PDB complexes with FMN) for FMN binding; correct
      cofactor-binding function, secondary to the core oxidase activity.
    supported_by:
    - reference_id: PMID:18215067
      supporting_text: catalyzes the FMN-dependent oxidation of glycolate to glyoxylate
        and glyoxylate to oxalate
    - reference_id: file:human/HAO1/HAO1-uniprot.txt
      supporting_text: Name=FMN;
- term:
    id: GO:0046296
    label: glycolate catabolic process
  evidence_type: IDA
  original_reference_id: PMID:18215067
  qualifier: involved_in
  review:
    summary: HAO1 catalyzes the committed oxidation of glycolate to glyoxylate, the
      primary catabolic fate of glycolate. This is a core biological process for HAO1.
    action: ACCEPT
    reason: Direct experimental support; glycolate oxidation to glyoxylate is identified
      as the primary reaction catalyzed by the enzyme, making glycolate catabolism
      a core process.
    supported_by:
    - reference_id: PMID:18215067
      supporting_text: oxidation of glycolate to glyoxylate is the primary reaction
        catalyzed by GO, while the oxidation of glyoxylate to oxalate is most likely
        not relevant under normal conditions
core_functions:
- description: FMN-dependent oxidation of glycolate to glyoxylate (and other L-2-hydroxy
    acids) using O2, producing H2O2, in the peroxisomal matrix of hepatocytes
  molecular_function:
    id: GO:0003973
    label: (S)-2-hydroxy-acid oxidase activity
  directly_involved_in:
  - id: GO:0046296
    label: glycolate catabolic process
  locations:
  - id: GO:0005782
    label: peroxisomal matrix
  supported_by:
  - reference_id: PMID:18215067
    supporting_text: oxidation of glycolate to glyoxylate is the primary reaction catalyzed
      by GO, while the oxidation of glyoxylate to oxalate is most likely not relevant
      under normal conditions
  - reference_id: PMID:10777549
    supporting_text: substrate, glycolate, but is also active on 2-hydroxy fatty acids
  - reference_id: file:human/HAO1/HAO1-uniprot.txt
    supporting_text: Broad substrate specificity (S)-2-hydroxy-acid oxidase that
- description: Binds the FMN cofactor required for its flavoenzyme oxidase activity
  molecular_function:
    id: GO:0010181
    label: FMN binding
  locations:
  - id: GO:0005782
    label: peroxisomal matrix
  supported_by:
  - reference_id: PMID:18215067
    supporting_text: catalyzes the FMN-dependent oxidation of glycolate to glyoxylate
      and glyoxylate to oxalate
  - reference_id: file:human/HAO1/HAO1-uniprot.txt
    supporting_text: Belongs to the FMN-dependent alpha-hydroxy acid
proposed_new_terms: []
suggested_questions:
- question: Under physiological hepatic conditions, what fraction of glyoxylate that
    is ultimately converted to oxalate originates from HAO1-generated glyoxylate versus
    other sources (e.g. hydroxyproline metabolism)?
- question: Does HAO1-generated peroxisomal H2O2 have any regulated signaling or redox
    role, or is it purely a metabolic by-product handled by peroxisomal catalase?
suggested_experiments:
- description: Quantitative flux analysis in primary human hepatocytes with graded
    HAO1 knockdown (mimicking lumasiran) to measure the contribution of HAO1 to glyoxylate
    and oxalate pools.
- description: Structure-guided kinetic profiling of HAO1 against the full spectrum
    of L-2-hydroxy acid and 2-hydroxy fatty acid substrates to define its in vivo substrate
    hierarchy beyond glycolate.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10777549
  title: Identification and characterization of HAOX1, HAOX2, and HAOX3, three human
    peroxisomal 2-hydroxy acid oxidases.
  findings:
  - statement: HAOX1 (HAO1) is a peroxisomal 2-hydroxy acid oxidase most active on
      glycolate, also active on 2-hydroxy fatty acids, and able to oxidize glyoxylate
      to oxalate, implicating it in primary hyperoxaluria type 1 pathophysiology.
      Expressed primarily in liver and pancreas.
    supporting_text: substrate, glycolate, but is also active on 2-hydroxy fatty acids
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; primary identification/characterization of human
      HAO1 (HAOX1) establishing peroxisomal localization, glycolate preference, and
      the PH1 connection. Abstract-only cache.
- id: PMID:17669354
  title: Purification and characterization of recombinant human liver glycolate oxidase.
  findings:
  - statement: Recombinant human liver glycolate oxidase is an FMN-dependent peroxisomal
      oxidase belonging to the L-2-hydroxy-acid-oxidizing flavoenzyme family; it contributes
      to oxalate production and is inhibited by its product oxalate.
    supporting_text: an FMN-dependent peroxisomal oxidase
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; biochemical characterization of recombinant human
      HAO1, confirming FMN dependence, homotetramer, and substrate specificity. Abstract-only
      cache.
- id: PMID:18215067
  title: 'Active site and loop 4 movements within human glycolate oxidase: implications
    for substrate specificity and drug design.'
  findings:
  - statement: Crystal structures and kinetics of human glycolate oxidase (HAO1) show
      that oxidation of glycolate to glyoxylate is the primary reaction, that glyoxylate-to-oxalate
      oxidation is likely not physiologically relevant, and that the enzyme is a drug
      target for primary hyperoxaluria type 1.
    supporting_text: oxidation of glycolate to glyoxylate is the primary reaction catalyzed
      by GO, while the oxidation of glyoxylate to oxalate is most likely not relevant
      under normal conditions
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified; structural/kinetic study establishing glycolate
      oxidation as the primary reaction and framing HAO1 as a hyperoxaluria drug target.
- id: Reactome:R-HSA-389842
  title: HAO1 tetramer oxidizes glycolate to glyoxylate
  findings: []
- id: Reactome:R-HSA-389862
  title: Conversion of glyoxylate to oxalate
  findings: []
- id: Reactome:R-HSA-9033235
  title: Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
  findings: []
- id: Reactome:R-HSA-9033236
  title: PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation
    Module)
  findings: []
- id: file:human/HAO1/HAO1-uniprot.txt
  title: UniProtKB Q9UJM8 (HAOX1_HUMAN) 2-Hydroxyacid oxidase 1
  findings:
  - statement: HAO1 is a broad-specificity (S)-2-hydroxy-acid oxidase that preferentially
      oxidizes glycolate, uses O2 to produce H2O2, is an FMN-dependent homotetramer
      in the peroxisome matrix, is highly expressed in liver, and feeds glyoxylate
      into peroxisomal glycine biosynthesis.
    supporting_text: preferentially oxidizes glycolate
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: UniProt reviewed entry; source for catalytic activities (RHEA/EC),
      FMN cofactor, homotetramer, peroxisomal matrix location, liver expression, and
      the glycine-biosynthesis/oxalate context.