HAO1 (Q9UJM8) review notes

Identity

HAO1 = hydroxyacid oxidase 1 = HAOX1 = glycolate oxidase (GO/GOX) = glyoxylate oxidase.
HGNC:4809; chr 20; 370 aa; peroxisomal matrix; homotetramer; FMN-dependent.
Member of the FMN-dependent alpha-hydroxy acid dehydrogenase family (TIM-barrel, PROSITE PRU00683).
C-terminal PTS1 microbody targeting signal (residues 368-370, motif "SKI"-type).

Broad-specificity (S)-2-hydroxy-acid oxidase that preferentially oxidises glycolate -> glyoxylate,
using O2 as physiological electron acceptor and producing H2O2 (EC 1.1.3.15; RHEA:16789 / RHEA:25311).
[UniProt FUNCTION; PMID:10777549 abstract "most active on the two-carbon substrate, glycolate"].
Also oxidises long-chain 2-hydroxy fatty acids (2-hydroxyhexadecanoate, 2-hydroxyoctanoate) with much
lower efficiency -> contributes to fatty-acid alpha-oxidation [PMID:10777549; PMID:18215067].
Can also oxidise glyoxylate -> oxalate (EC 1.2.3.5) in vitro, but PMID:18215067 explicitly states this
is "most likely not relevant under normal conditions"; glycolate->glyoxylate is "the primary reaction".
FMN is the cofactor [PMID:17669354, PMID:18215067]; product oxalate inhibits PMID:17669354.
Highly/tissue-enriched expression in liver (HPA: tissue-enriched liver); also pancreas/kidney PMID:10777549.

Generates glyoxylate, the immediate precursor of oxalate. In primary hyperoxaluria (PH1: AGXT deficiency),
glyoxylate is not detoxified to glycine and is converted to oxalate -> kidney stones/oxalosis.
HAO1 (upstream of glyoxylate) is a validated therapeutic target: the siRNA drug lumasiran silences HAO1
to reduce hepatic oxalate production. HAO1 loss is protective (substrate-reduction rationale), so there is
no classic HAO1 loss-of-function Mendelian disease.
PMID:10777549: HAOX1 in liver/kidney peroxisomes + ability to oxidise glyoxylate to oxalate implicate it in
PH1 pathophysiology.

Core MF in GOA and used here: GO:0003973 (S)-2-hydroxy-acid oxidase activity (verified label current).
Core BP: GO:0046296 glycolate catabolic process (IDA PMID:18215067).
Located in peroxisome / peroxisomal matrix (GO:0005777 / GO:0005782).
FMN binding (GO:0010181) secondary (cofactor).
glyoxylate oxidase (GO:0047969, glyoxylate->oxalate) = real IDA but non-core (not physiologically relevant).
fatty acid alpha-oxidation (GO:0001561, IDA) + glycine biosynthetic process (GO:0006545, UniPathway) = non-core.
oxidoreductase activity (GO:0016491), alcohol oxidase activity (GO:0047639), fatty acid oxidation (GO:0019395),
cytosol (GO:0005829, import transit), response to oxidative stress (GO:0006979) = over-annotations.

PMID:10777549 (Jones 2000), PMID:17669354 (Vignaud 2007), PMID:18215067 (Murray 2008): abstract-only cached
(full_text_available: false; PMID:18215067 has abstract+partial discussion). PMID:10978532 (Williams 2000,
glycolate oxidase cDNA) NOT cached — cited only via UniProt where relevant.
supporting_text quotes below are verbatim substrings of the cached abstracts (grep-verified) or file: UniProt.