# HAO2 > Gene · canonical: https://sugi.bio/atlas/gene/HAO2/ > Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00 ## Summary **HAO2** (hydroxyacid oxidase 2, HGNC:4810) is a protein-coding gene on chromosome 1p12, encoding **2-Hydroxyacid oxidase 2** (Q9NYQ3). Oxidase that catalyzes the oxidation of medium and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, to the corresponding 2-oxoacids. This gene is one of three related genes that have 2-hydroxyacid oxidase activity. The encoded protein localizes to the peroxisome has the highest activity toward the substrate 2-hydroxypalmitate. Alternative splicing results in multiple transcript variants. *Source: [NCBI Gene 51179](https://www.ncbi.nlm.nih.gov/gene/51179) — RefSeq curated summary.* **At a glance** - **GWAS associations:** 8 - **Clinical variants (ClinVar):** 60 total - **GTEx eGene:** eQTL in 13 tissues, sQTL in 1 (q < 0.05) - **Constraint (gnomAD):** pLI 0.00 (LoF-tolerant), LOEUF 1.33 (unconstrained) - **MANE Select transcript:** `NM_016527` - **Interaction hub:** 1,764 STRING partners (top 10% of genes corpus-wide) - **Notable:** 60 clinical variants but no curated precision-oncology (CIViC) evidence yet ## Identifiers ### Gene identifiers | Field | Value | | --- | --- | | HGNC ID | HGNC:4810 | | Approved symbol | HAO2 | | Name | hydroxyacid oxidase 2 | | Location | 1p12 | | Locus type | gene with protein product | | Status | Approved | | Aliases | HAOX2, GIG16 | | Ensembl gene | ENSG00000116882 | | Ensembl biotype | protein_coding | | OMIM | 605176 | | Entrez | 51179 | ## Gene structure ### Transcript identifiers **Ensembl transcripts: 54** — 45 protein_coding, 8 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined **MANE Select:** `ENST00000325945` **Transcript support level (Ensembl TSL; 1 = fully mRNA-supported):** TSL 1: 3, TSL 2: 1, TSL 3: 1 `ENST00000325945`, `ENST00000361035`, `ENST00000457318`, `ENST00000482991`, `ENST00000622548`, `ENST00000864531`, `ENST00000864532`, `ENST00000864533`, `ENST00000864534`, `ENST00000864535`, `ENST00000864536`, `ENST00000864537`, `ENST00000864538`, `ENST00000864539`, `ENST00000864540`, `ENST00000864541`, `ENST00000864542`, `ENST00000864543`, `ENST00000864544`, `ENST00000864545`, `ENST00000864546`, `ENST00000864547`, `ENST00000864548`, `ENST00000864549`, `ENST00000864550`, `ENST00000864551`, `ENST00000864552`, `ENST00000864553`, `ENST00000864554`, `ENST00000864555`, `ENST00000864556`, `ENST00000864557`, `ENST00000864558`, `ENST00000864559`, `ENST00000864560`, `ENST00000864561`, `ENST00000979307`, `ENST00000979308`, `ENST00000979310`, `ENST00000979311`, `ENST00000979316`, `ENST00000979317`, `ENST00001092846`, `ENST00001092847`, `ENST00001118773`, `ENST00001118774`, `ENST00001118775`, `ENST00001118776`, `ENST00001118777`, `ENST00001118778`, `ENST00001118779`, `ENST00001118780`, `ENST00001118781`, `ENST00001145700` **RefSeq mRNA: 3** — MANE Select: `NM_016527` `NM_001005783`, `NM_001377472`, `NM_016527` **CCDS:** `CCDS76196`, `CCDS901` #### Canonical transcript exons `ENST00000325945` — 8 exons | Exon | Start | End | | --- | --- | --- | | ENSE00000785225 | 119382915 | 119383066 | | ENSE00000785226 | 119384776 | 119385053 | | ENSE00000785228 | 119392110 | 119392268 | | ENSE00000785229 | 119392618 | 119392687 | | ENSE00000800638 | 119386622 | 119386831 | | ENSE00001814760 | 119368785 | 119368902 | | ENSE00001839391 | 119393785 | 119394130 | | ENSE00003513214 | 119381078 | 119381216 | ### Expression profiles **Bgee:** expression breadth **ubiquitous**, 132 present calls, max score 98.37. **FANTOM5 (CAGE):** breadth **tissue_specific**, TPM avg 0.1438 / max 48.4179, expressed in 11 samples. **Highest expression (Bgee):** lobe of liver, liver, kidney epithelium, nephron tubule, adult mammalian kidney. #### Genetic regulation across tissues (GTEx eQTL / sQTL) HAO2 is an **eGene** in GTEx v10 — its expression is genetically regulated (eQTL) in **13** tissues and its splicing (sQTL) in **1** (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant's alternative allele. 14 significant tissue × QTL associations: | Tissue | QTL | q-value | Slope | Lead variant | | --- | --- | --- | --- | --- | | Nerve Tibial | eqtl | 1.3e-12 | -0.47 | 1:119177063:T:C | | Adrenal Gland | eqtl | 4.6e-10 | -0.43 | 1:119380908:A:C | | Thyroid | eqtl | 2.4e-08 | +0.48 | 1:119156143:C:T | | Adipose Subcutaneous | eqtl | 1.7e-07 | -0.32 | 1:119130721:G:A | | Liver | sqtl | 8.5e-06 | +0.62 | 1:119370421:T:C | | Breast Mammary Tissue | eqtl | 2.5e-05 | -0.32 | 1:119130721:G:A | | Artery Tibial | eqtl | 6.5e-05 | -0.29 | 1:119138966:C:T | | Skin Not Sun Exposed Suprapubic | eqtl | 3.7e-03 | -0.32 | 1:119656586:T:C | | Artery Coronary | eqtl | 1.1e-02 | -0.45 | 1:119219552:G:A | | Minor Salivary Gland | eqtl | 1.7e-02 | -0.54 | 1:119066292:T:C | | Testis | eqtl | 3.0e-02 | -0.34 | 1:119233151:G:A | | Skin Sun Exposed Lower leg | eqtl | 3.2e-02 | +0.55 | 1:118727436:G:A | | Adipose Visceral Omentum | eqtl | 4.7e-02 | +0.46 | 1:120270073:T:C | | Whole Blood | eqtl | 5.0e-02 | -0.17 | 1:119261927:G:A | #### FANTOM5 promoters 3 alternative TSS: | Promoter ID | TPM avg | Samples expressed | | --- | --- | --- | | 4917 | 0.0828 | 7 | | 4916 | 0.0584 | 8 | | 201635 | 0.0025 | 2 | #### Top tissues by expression showing 100 of 263 tissues by Bgee expression score (0-100, higher = more expressed): | Tissue | Anatomy ID | Expression score | Quality | | --- | --- | --- | --- | | right lobe of liver | UBERON:0001114 | 98.37 | gold quality | | liver | UBERON:0002107 | 95.68 | gold quality | | kidney epithelium | UBERON:0004819 | 94.72 | gold quality | | nephron tubule | UBERON:0001231 | 94.69 | gold quality | | adult mammalian kidney | UBERON:0000082 | 93.55 | gold quality | | adult organism | UBERON:0007023 | 93.55 | gold quality | | renal glomerulus | UBERON:0000074 | 93.40 | gold quality | | metanephric glomerulus | UBERON:0004736 | 92.92 | gold quality | | male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 91.55 | gold quality | | kidney | UBERON:0002113 | 90.15 | gold quality | | renal medulla | UBERON:0000362 | 87.06 | gold quality | | cortex of kidney | UBERON:0001225 | 84.64 | gold quality | | metanephros | UBERON:0000081 | 79.73 | gold quality | | upper leg skin | UBERON:0004262 | 73.80 | gold quality | | upper arm skin | UBERON:0004263 | 70.05 | gold quality | | mammalian vulva | UBERON:0000997 | 69.53 | gold quality | | ileal mucosa | UBERON:0000331 | 69.26 | silver quality | | thymus | UBERON:0002370 | 69.11 | silver quality | | cerebellar vermis | UBERON:0004720 | 68.00 | gold quality | | metanephros cortex | UBERON:0010533 | 67.19 | gold quality | | olfactory bulb | UBERON:0002264 | 66.68 | gold quality | | type B pancreatic cell | CL:0000169 | 66.48 | gold quality | | nipple | UBERON:0002030 | 65.71 | gold quality | | right adrenal gland cortex | UBERON:0035827 | 65.19 | gold quality | | deltoid | UBERON:0001476 | 63.66 | silver quality | | diaphragm | UBERON:0001103 | 63.44 | gold quality | | male germ cell | CL:0000015 | 63.42 | gold quality | | right adrenal gland | UBERON:0001233 | 63.27 | gold quality | | left adrenal gland | UBERON:0001234 | 63.03 | gold quality | | pancreatic ductal cell | CL:0002079 | 62.89 | silver quality | | sperm | CL:0000019 | 62.83 | gold quality | | adrenal cortex | UBERON:0001235 | 62.20 | gold quality | | left adrenal gland cortex | UBERON:0035825 | 61.72 | gold quality | | adrenal gland | UBERON:0002369 | 60.72 | gold quality | | nasal cavity epithelium | UBERON:0005384 | 60.70 | gold quality | | saphenous vein | UBERON:0007318 | 59.71 | gold quality | | pharyngeal mucosa | UBERON:0000355 | 59.13 | gold quality | | inferior vagus X ganglion | UBERON:0005363 | 59.13 | gold quality | | dorsal plus ventral thalamus | UBERON:0001897 | 59.06 | gold quality | | pericardium | UBERON:0002407 | 58.90 | gold quality | | skin of abdomen | UBERON:0001416 | 58.88 | gold quality | | ventral tegmental area | UBERON:0002691 | 58.72 | gold quality | | decidua | UBERON:0002450 | 58.49 | gold quality | | subthalamic nucleus | UBERON:0001906 | 58.44 | gold quality | | dorsal root ganglion | UBERON:0000044 | 58.42 | gold quality | | trigeminal ganglion | UBERON:0001675 | 58.38 | gold quality | | superior vestibular nucleus | UBERON:0007227 | 58.38 | gold quality | | superior surface of tongue | UBERON:0007371 | 58.36 | gold quality | | body of tongue | UBERON:0011876 | 58.35 | gold quality | | pons | UBERON:0000988 | 58.33 | gold quality | | pylorus | UBERON:0001166 | 58.33 | gold quality | | substantia nigra pars reticulata | UBERON:0001966 | 58.19 | gold quality | | substantia nigra pars compacta | UBERON:0001965 | 58.17 | gold quality | | lateral nuclear group of thalamus | UBERON:0002736 | 58.11 | gold quality | | cardia of stomach | UBERON:0001162 | 58.10 | gold quality | | tongue | UBERON:0001723 | 57.98 | gold quality | | lateral globus pallidus | UBERON:0002476 | 57.97 | gold quality | | trachea | UBERON:0003126 | 57.53 | gold quality | | medulla oblongata | UBERON:0001896 | 57.20 | gold quality | | myocardium | UBERON:0002349 | 57.20 | gold quality | | vena cava | UBERON:0004087 | 56.96 | gold quality | | gluteal muscle | UBERON:0002000 | 56.63 | gold quality | | triceps brachii | UBERON:0001509 | 56.48 | gold quality | | zone of skin | UBERON:0000014 | 56.46 | gold quality | | globus pallidus | UBERON:0001875 | 56.22 | gold quality | | quadriceps femoris | UBERON:0001377 | 55.68 | gold quality | | medial globus pallidus | UBERON:0002477 | 55.42 | gold quality | | hair follicle | UBERON:0002073 | 55.37 | gold quality | | biceps brachii | UBERON:0001507 | 55.22 | gold quality | | skeletal muscle tissue of biceps brachii | UBERON:0004502 | 55.07 | gold quality | | oocyte | CL:0000023 | 54.89 | gold quality | | trabecular bone tissue | UBERON:0002483 | 54.66 | gold quality | | epithelial cell of pancreas | CL:0000083 | 54.21 | gold quality | | mucosa of sigmoid colon | UBERON:0004993 | 53.73 | gold quality | | mammary duct | UBERON:0001765 | 53.46 | gold quality | | epithelium of mammary gland | UBERON:0003244 | 53.35 | gold quality | | vastus lateralis | UBERON:0001379 | 53.21 | gold quality | | buccal mucosa cell | CL:0002336 | 53.11 | gold quality | | lymph node | UBERON:0000029 | 52.85 | gold quality | | synovial joint | UBERON:0002217 | 52.30 | gold quality | | skin of leg | UBERON:0001511 | 52.10 | gold quality | | heart right ventricle | UBERON:0002080 | 51.80 | gold quality | | penis | UBERON:0000989 | 51.74 | gold quality | | layer of synovial tissue | UBERON:0007616 | 51.67 | gold quality | | primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 51.48 | silver quality | | oral cavity | UBERON:0000167 | 50.57 | gold quality | | cervix epithelium | UBERON:0004801 | 49.87 | gold quality | | nasal cavity mucosa | UBERON:0001826 | 49.77 | gold quality | | colonic mucosa | UBERON:0000317 | 49.60 | gold quality | | orbitofrontal cortex | UBERON:0004167 | 49.54 | gold quality | | olfactory segment of nasal mucosa | UBERON:0005386 | 49.51 | gold quality | | oviduct epithelium | UBERON:0004804 | 49.41 | gold quality | | Brodmann (1909) area 46 | UBERON:0006483 | 49.30 | gold quality | | duodenum | UBERON:0002114 | 49.29 | gold quality | | blood vessel layer | UBERON:0004797 | 49.29 | gold quality | | cervix squamous epithelium | UBERON:0006922 | 49.20 | gold quality | | parotid gland | UBERON:0001831 | 48.97 | gold quality | | choroid plexus epithelium | UBERON:0003911 | 48.89 | gold quality | | cardiac muscle of right atrium | UBERON:0003379 | 48.55 | gold quality | | CA1 field of hippocampus | UBERON:0003881 | 48.50 | gold quality | #### Single-cell (SCXA) Detected in 2 experiment(s), a significant marker in 2. | Experiment | Marker? | Max mean expression | | --- | --- | --- | | [E-HCAD-10](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-10) | yes | 32.77 | | [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/E-ANND-3) | yes | 4.53 | #### HPA expression RNA tissue specificity: **Group enriched** 55 HPA tissues / cells by nTPM: | Tissue / cell | Axis | nTPM | | --- | --- | --- | | Liver | tissue | 397.7 | | Kidney | tissue | 283.1 | | Thymus | tissue | 21.7 | | Amygdala | tissue | 10.2 | | Corpus callosum | tissue | 10.0 | | Basal ganglia | tissue | 9.8 | | Cerebral cortex | tissue | 9.6 | | Insular cortex | tissue | 9.6 | | Retrosplenial and cingulate cortex | tissue | 9.3 | | Putamen | tissue | 9.2 | | Olfactory bulb | tissue | 9.2 | | Retrosplenial cortex | tissue | 9.2 | | Cerebellum | tissue | 9.1 | | Spinal cord | tissue | 9.0 | | Ventral forebrain | tissue | 9.0 | | Hippocampal formation | tissue | 8.7 | | Entorhinal cortex | tissue | 8.7 | | Temporal cortex | tissue | 8.6 | | Prefrontal cortex | tissue | 8.5 | | Motor cortex | tissue | 8.0 | | Occipital cortex | tissue | 7.9 | | Periaqueductal gray | tissue | 7.8 | | Septum | tissue | 7.8 | | Midbrain | tissue | 7.2 | | Somatosensory cortex | tissue | 7.2 | | Medulla oblongata | tissue | 7.0 | | Hypothalamus | tissue | 7.0 | | Substantia nigra | tissue | 6.8 | | Thalamus | tissue | 6.2 | | Pons | tissue | 5.9 | | Superior colliculi | tissue | 5.9 | | Postcentral gyrus | tissue | 3.0 | | Locus coeruleus | tissue | 1.6 | | Breast | tissue | 0.6 | | Hippocampus | tissue | 0.5 | | Adrenal gland | tissue | 0.5 | | Nucleus accumbens | tissue | 0.4 | | Spleen | tissue | 0.4 | | Skin 1 | tissue | 0.3 | | Lymph node | tissue | 0.3 | | Placenta | tissue | 0.3 | | Colon | tissue | 0.2 | | Tonsil | tissue | 0.2 | | Testis | tissue | 0.1 | | Stomach 1 | tissue | 0.1 | | Heart muscle | tissue | 0.1 | | Rectum | tissue | 0.1 | | Urinary bladder | tissue | 0.1 | | Pancreas | tissue | 0.1 | | Epididymis | tissue | 0.1 | | Choroid plexus | tissue | 0.1 | | Small intestine | tissue | 0.1 | | Duodenum | tissue | 0.1 | | Prostate | tissue | 0.1 | | Appendix | tissue | 0.1 | **Brain sub-regions (HPA Brain Atlas):** detected in 184; highest nTPM — White matter (10.0), Ventral spinal cord (9.0), Dorsal spinal cord (8.7), Subiculum (8.5), Ventral hippocampus (8.1). ### Regulation **Is transcription factor: no** #### miRNA regulators (miRDB) Targeting HAO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific). 24 miRNAs: | miRNA | Max score | Avg score | miRNA target_count | | --- | --- | --- | --- | | HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 | | HSA-MIR-524-5P | 99.98 | 73.43 | 4882 | | HSA-MIR-4648 | 99.91 | 67.00 | 710 | | HSA-MIR-5680 | 99.91 | 69.83 | 3421 | | HSA-MIR-374A-5P | 99.90 | 71.34 | 2923 | | HSA-MIR-4697-3P | 99.89 | 67.09 | 1123 | | HSA-MIR-377-3P | 99.37 | 70.18 | 1905 | | HSA-MIR-6737-3P | 98.95 | 68.56 | 1577 | | HSA-MIR-7157-3P | 98.95 | 68.70 | 1582 | | HSA-MIR-5008-3P | 98.73 | 67.50 | 1433 | | HSA-MIR-5572 | 98.55 | 65.84 | 970 | | HSA-MIR-1233-5P | 98.19 | 66.71 | 1201 | | HSA-MIR-6778-5P | 98.19 | 66.59 | 1239 | | HSA-MIR-615-5P | 98.10 | 63.76 | 591 | | HSA-MIR-6847-5P | 97.93 | 66.74 | 1808 | | HSA-MIR-450A-2-3P | 97.91 | 67.56 | 1459 | | HSA-MIR-4257 | 97.86 | 68.05 | 1190 | | HSA-MIR-299-3P | 97.73 | 66.67 | 773 | | HSA-MIR-4253 | 97.48 | 65.11 | 692 | | HSA-MIR-6862-5P | 97.48 | 64.84 | 713 | | HSA-MIR-6515-5P | 97.08 | 65.48 | 1219 | | HSA-MIR-4654 | 95.86 | 65.72 | 751 | | HSA-MIR-4769-5P | 95.37 | 66.09 | 570 | | HSA-MIR-4442 | 92.35 | 67.08 | 98 | ### Functional genomics **gnomAD constraint:** pLI 2.42e-10, LOEUF 1.33, missense Z -0.36 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). [gnomAD](https://gnomad.broadinstitute.org/) **Regional missense constraint (gnomAD RMC):** no regional variation along `ENST00000325945` — one region, missense o/e 1.11. ### Literature-anchored findings (GeneRIF, showing 4) - Dysregulation of HAO2 is a very early event in the development of hepatocellular carcinoma (HCC). (PMID:26658681) - Overexpression of HAO2 by plasmid promoted lipid catabolic process, eliminated lipid accumulation, inhibited KRAS expression, controlled the proliferation, migration, and invasion activity of clear cell renal cell carcinoma (ccRCC) tumor cells (PMID:31127626) - miR-1293 Suppresses Tumor Malignancy by Targeting Hydrocyanic Oxidase 2: Therapeutic Potential of a miR-1293/Hydrocyanic Oxidase 2 Axis in Renal Cell Carcinoma. (PMID:31971830) - Hydroxyacid Oxidase 2 (HAO2) Inhibits the Tumorigenicity of Hepatocellular Carcinoma and Is Negatively Regulated by miR-615-5p. (PMID:35528616) ### Cross-species orthologs **5 orthologs** | Organism | Symbol | Gene ID | | --- | --- | --- | | danio_rerio | hao2 | ENSDARG00000027992 | | mus_musculus | Hao2 | ENSMUSG00000027870 | | rattus_norvegicus | Hao2 | ENSRNOG00000019470 | | drosophila_melanogaster | Hao | FBGN0061356 | | caenorhabditis_elegans | | WBGENE00018286 | **Paralogs (2):** HAO1 (ENSG00000101323), CARNS1 (ENSG00000172508) #### Additional cross-species homologs Sequence homologs in species beyond Ensembl Compara's model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions' gene symbols aren't in biobtree yet, so each row shows the UniProt accession. | Organism | UniProt | Identity | Method | | --- | --- | --- | --- | | Oryza sativa Indica Group | [B8AKX6](https://www.uniprot.org/uniprotkb/B8AKX6/entry) | 100.0% | Diamond | | Oryza sativa Japonica Group | [Q10CE4](https://www.uniprot.org/uniprotkb/Q10CE4/entry) | 100.0% | Diamond | | Fusarium oxysporum f. sp. lycopersici 4287 | [A0A0D2YG00](https://www.uniprot.org/uniprotkb/A0A0D2YG00/entry) | 97.2% | Diamond | | Fusarium verticillioides 7600 | [W7NCP1](https://www.uniprot.org/uniprotkb/W7NCP1/entry) | 97.2% | Diamond | | Arabidopsis thaliana | [Q9LRR9](https://www.uniprot.org/uniprotkb/Q9LRR9/entry) | 95.1% | Diamond | | Fusarium fujikuroi IMI 58289 | [S0DRI9](https://www.uniprot.org/uniprotkb/S0DRI9/entry) | 93.9% | Diamond | | Zea mays | [A0A3L6E0R4](https://www.uniprot.org/uniprotkb/A0A3L6E0R4/entry) | 93.2% | Diamond | | Borreliella bavariensis PBi | [Q660I6](https://www.uniprot.org/uniprotkb/Q660I6/entry) | 90.1% | Diamond | | Spinacia oleracea | [P05414](https://www.uniprot.org/uniprotkb/P05414/entry) | 89.2% | Diamond | | Bos taurus | [Q3ZBW2](https://www.uniprot.org/uniprotkb/Q3ZBW2/entry) | 82.4% | Diamond | | Hansenula anomala | [P09437](https://www.uniprot.org/uniprotkb/P09437/entry) | 60.0% | Diamond | | Talaromyces stipitatus ATCC 10500 | [B8MKR3](https://www.uniprot.org/uniprotkb/B8MKR3/entry) | 58.5% | Diamond | | Saccharomyces cerevisiae S288C | [P00175](https://www.uniprot.org/uniprotkb/P00175/entry) | 56.0% | Diamond | | Dictyostelium discoideum | [Q54E41](https://www.uniprot.org/uniprotkb/Q54E41/entry) | 53.7% | Diamond | | Lactobacillus jensenii | [A0A5N1I561](https://www.uniprot.org/uniprotkb/A0A5N1I561/entry) | 52.4% | Diamond | | Lentilactobacillus hilgardii DSM 20176 = ATCC 8290 | [C0XIJ3](https://www.uniprot.org/uniprotkb/C0XIJ3/entry) | 52.4% | Diamond | | Nostoc sp. PCC 7120 = FACHB-418 | [Q8Z0C8](https://www.uniprot.org/uniprotkb/Q8Z0C8/entry) | 52.1% | Diamond | | Chlamydomonas reinhardtii | [F8WQN2](https://www.uniprot.org/uniprotkb/F8WQN2/entry) | 52.0% | Diamond | | Aerococcus viridans ATCC 11563 = CCUG 4311 | [Q44467](https://www.uniprot.org/uniprotkb/Q44467/entry) | 51.5% | Diamond | | Streptococcus iniae | [O33655](https://www.uniprot.org/uniprotkb/O33655/entry) | 51.1% | Diamond | | Lacticaseibacillus rhamnosus LMS2-1 | [C2K1F0](https://www.uniprot.org/uniprotkb/C2K1F0/entry) | 48.7% | Diamond | | Penicillium citrinum | [P0DUR7](https://www.uniprot.org/uniprotkb/P0DUR7/entry) | 46.7% | Diamond | | Schizosaccharomyces pombe 972h- | [Q9HDX2](https://www.uniprot.org/uniprotkb/Q9HDX2/entry) | 46.7% | Diamond | | Amycolatopsis orientalis | [O52792](https://www.uniprot.org/uniprotkb/O52792/entry) | 45.4% | Diamond | | Roseobacter sp. GAI101 | [B7RR92](https://www.uniprot.org/uniprotkb/B7RR92/entry) | 45.0% | Diamond | | Alicycliphilus denitrificans K601 | [F4G5A4](https://www.uniprot.org/uniprotkb/F4G5A4/entry) | 45.0% | Diamond | | Coccidioides immitis RS | [J3KAR9](https://www.uniprot.org/uniprotkb/J3KAR9/entry) | 44.1% | Diamond | | Rhodotorula graminis | [P32953](https://www.uniprot.org/uniprotkb/P32953/entry) | 42.4% | Diamond | | Lysinibacillus sphaericus C3-41 | [B1HZY7](https://www.uniprot.org/uniprotkb/B1HZY7/entry) | 42.0% | Diamond | | Mycolicibacterium smegmatis | [P21795](https://www.uniprot.org/uniprotkb/P21795/entry) | 40.1% | Diamond | ### Genomic neighbors (locus context) Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that). | Symbol | Type | Entrez | | --- | --- | --- | | [WARS2-AS1](/atlas/gene/WARS2-AS1/) | ncRNA | 101929147 | | [LINC01780](/atlas/gene/LINC01780/) | ncRNA | 105378934 | | [HSD3B2](/atlas/gene/HSD3B2/) | protein-coding | 3284 | | [HAO2-IT1](/atlas/gene/HAO2-IT1/) | ncRNA | 100874270 | | [WARS2](/atlas/gene/WARS2/) | protein-coding | 10352 | ## Protein ### Protein identifiers **2-Hydroxyacid oxidase 2** — `Q9NYQ3` (reviewed: Q9NYQ3) **Alternative names:** (S)-2-hydroxy-acid oxidase, peroxisomal, Cell growth-inhibiting gene 16 protein, Long chain alpha-hydroxy acid oxidase, Long-chain L-2-hydroxy acid oxidase **All UniProt accessions (2):** `Q9NYQ3`, `Q5QP02` #### UniProt curated annotations — [full annotation on UniProt →](https://www.uniprot.org/uniprotkb/Q9NYQ3/entry) **Function.** Oxidase that catalyzes the oxidation of medium and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, to the corresponding 2-oxoacids. Its role in the oxidation of 2-hydroxy fatty acids may contribute to the general pathway of fatty acid alpha-oxidation. Active in vitro with the artificial electron acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be the physiological electron acceptor, leading to the production of H2O2. Is not active on glycolate, glyoxylate, L-lactate and 2-hydroxybutanoate. **Subunit / interactions.** Homotetramer. **Subcellular location.** Peroxisome. **Tissue specificity.** Expressed in the liver and kidney. **Pathway.** Lipid metabolism; fatty acid metabolism. **Similarity.** Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family. #### Isoforms (2) | UniProt ID | Names | Canonical? | | --- | --- | --- | | Q9NYQ3-1 | 1 | yes | | Q9NYQ3-2 | 2 | | **RefSeq proteins (3):** `NP_001005783`, `NP_001364401`, `NP_057611`* (*=MANE) #### Domains & families (InterPro) | ID | Name | Type | | --- | --- | --- | | IPR000262 | FMN-dep_DH | Domain | | IPR008259 | FMN_hydac_DH_AS | Active_site | | IPR012133 | Alpha-hydoxy_acid_DH_FMN | Family | | IPR013785 | Aldolase_TIM | Homologous_superfamily | | IPR037396 | FMN_HAD | Domain | **Pfam:** `PF01070` #### Enzyme classification (BRENDA) - EC 1.1.3.15 — (S)-2-hydroxy-acid oxidase *(BRENDA: 44 organisms, 164 substrates, 154 inhibitors, 169 Km, 41 kcat entries)* #### Substrate kinetics (BRENDA) 52 substrates with measured Km, best-characterized 15. *Km ranges are aggregated across organisms/conditions.* | Substrate | Km (mM) | Measurements | | --- | --- | --- | | GLYCOLATE | 0.0056–2.1 | 24 | | (S)-LACTATE | 0.0052–103 | 15 | | L-LACTATE | 0.34–16.5 | 14 | | L-2-HYDROXYISOCAPROATE | 0.3–2.5 | 11 | | O2 | 0.022–0.64 | 10 | | DL-2-HYDROXYBUTYRATE | 0.6–14 | 8 | | GLYOXYLATE | 1.41–6.51 | 7 | | L-MANDELATE | 0.16–20 | 7 | | DL-2-HYDROXYCAPROATE | 0.15–3.2 | 4 | | DL-2-HYDROXYVALERATE | 0.25–13 | 4 | | GLYCERATE | 2.76–7.14 | 4 | | L-LEUCINE | 5.3–15 | 4 | | DL-3-CHLOROLACTATE | 0.7–28 | 3 | | DL-2-HYDROXY-4-METHYLTHIOBUTANOIC ACID | 0.7–1.1 | 2 | | DL-2-HYDROXYISOVALERATE | 0.6–8 | 2 | #### Catalyzed reactions (Rhea) - a (2S)-2-hydroxycarboxylate + O2 = a 2-oxocarboxylate + H2O2 *(RHEA:16789)* - 2-hydroxyoctanoate + O2 = 2-oxooctanoate + H2O2 *(RHEA:67940)* - 2-hydroxyhexadecanoate + O2 = 2-oxohexadecanoate + H2O2 *(RHEA:67944)* **UniProt features (20 total):** binding site 10, sequence variant 2, sequence conflict 2, chain 1, domain 1, modified residue 1, splice variant 1, short sequence motif 1, active site 1 ### Structure #### Predicted structure (AlphaFold) | Model | pLDDT | Fraction very-high | | --- | --- | --- | | AF-Q9NYQ3-F1 | 92.99 | 0.88 | ### Human Protein Atlas **Protein class:** Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins **Protein evidence:** Evidence at protein level **Subcellular location (HPA, imaging):** cytosol; vesicles **Antibody reliability (HPA):** IF approved ### Functional residue map Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. *Source: UniProtKB sequence features.* #### Catalytic / active sites (1) | Position | Role | | --- | --- | | 246 | proton acceptor | #### Ligand- & substrate-binding residues (10) | Position | Role | | --- | --- | | 222 | FMN | | 249 | a 2-oxocarboxylate | | 277–281 | FMN | | 300–301 | FMN | | 77–79 | FMN | | 106 | FMN | | 128 | FMN | | 130 | a 2-oxocarboxylate | | 156 | FMN | | 165 | a 2-oxocarboxylate | #### Post-translational modifications (1) | Type | Positions | | --- | --- | | Phosphothreonine | 178 | ## Function ### Pathways and Gene Ontology #### Reactome pathways **1 curated (TAS)** of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference). 6 pathways: | ID | Pathway | Evidence | | --- | --- | --- | | R-HSA-390918 | Peroxisomal lipid metabolism | curated | | R-HSA-8978868 | Fatty acid metabolism | — | | R-HSA-1430728 | Metabolism | — | | R-HSA-556833 | Metabolism of lipids | — | | R-HSA-9033241 | Peroxisomal protein import | electronic | | R-HSA-9609507 | Protein localization | — | **MSigDB gene sets: 91** (showing top): `GOBP_LIPID_MODIFICATION`, `GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS`, `BLALOCK_ALZHEIMERS_DISEASE_UP`, `TGTGTGA_MIR377`, `ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_DN`, `CAIRO_HEPATOBLASTOMA_DN`, `GOBP_LIPID_METABOLIC_PROCESS`, `GOBP_ORGANIC_ACID_METABOLIC_PROCESS`, `chr1p12`, `GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS`, `GOBP_LIPID_OXIDATION`, `TGGAAA_NFAT_Q4_01`, `GOCC_MICROBODY`, `GOCC_MICROBODY_LUMEN`, `GOBP_FATTY_ACID_METABOLIC_PROCESS` **GO Biological Process (3):** fatty acid oxidation (GO:0019395), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631) **GO Molecular Function (6):** (S)-2-hydroxy-acid oxidase activity (GO:0003973), FMN binding (GO:0010181), protein binding (GO:0005515), glutamate synthase activity (GO:0015930), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-NH2 group of donors (GO:0016638) **GO Cellular Component (3):** peroxisomal matrix (GO:0005782), cytosol (GO:0005829), peroxisome (GO:0005777) #### Reactome top-level categories 4 top-level categories: | Category | Pathways | | --- | --- | | Fatty acid metabolism | 1 | | Protein localization | 1 | | Metabolism | 1 | | Metabolism of lipids | 1 | #### GO top-level categories 17 GO namespaces: | Category | Terms | | --- | --- | | fatty acid metabolic process | 1 | | lipid oxidation | 1 | | primary metabolic process | 1 | | lipid metabolic process | 1 | | monocarboxylic acid metabolic process | 1 | | oxidoreductase activity, acting on the CH-OH group of donors, oxygen as acceptor | 1 | | ribonucleotide binding | 1 | | anion binding | 1 | | binding | 1 | | oxidoreductase activity, acting on the CH-NH2 group of donors | 1 | | catalytic activity | 1 | | oxidoreductase activity | 1 | | peroxisome | 1 | | microbody lumen | 1 | | cytoplasm | 1 | | cellular anatomical structure | 1 | | microbody | 1 | #### Experimentally-supported GO annotations GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA). 3 experimentally-supported GO terms: | GO term | NS | Evidence | | --- | --- | --- | | [fatty acid oxidation](https://amigo.geneontology.org/amigo/term/GO:0019395) | BP | direct assay | | [peroxisomal matrix](https://amigo.geneontology.org/amigo/term/GO:0005782) | CC | direct assay | | [(S)-2-hydroxy-acid oxidase activity](https://amigo.geneontology.org/amigo/term/GO:0003973) | MF | direct assay | ### Protein interactions and networks #### STRING showing 15 of 1,764 interactions by confidence (×1000): | Protein A | Protein B | Partner UniProt | Score | | --- | --- | --- | --- | | HAO2 | ACO1 | P21399 | 690 | | HAO2 | IREB2 | P48200 | 681 | | HAO2 | AGXT | P21549 | 486 | | HAO2 | PECR | Q9BY49 | 459 | | HAO2 | PIPOX | Q9P0Z9 | 448 | | HAO2 | ACSL6 | Q9UKU0 | 427 | | HAO2 | HAAO | P46952 | 387 | | HAO2 | ACAA1 | P09110 | 382 | | HAO2 | FAR1 | Q8WVX9 | 373 | | HAO2 | NUDT12 | Q9BQG2 | 370 | | HAO2 | AADAT | Q8N5Z0 | 370 | | HAO2 | DHRS7 | Q9Y394 | 369 | | HAO2 | GRHPR | Q9UBQ7 | 367 | | HAO2 | CRAT | P43155 | 367 | | HAO2 | PCK1 | P35558 | 365 | #### IntAct Human interaction partners of HAO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records). 3 partners by confidence: | Partner | Interaction type | MIscore | Records | | --- | --- | --- | --- | | SEC14L4 | physical association | 0.560 | 3 | | EIF4G3 | association | 0.530 | 2 | | TRIM7 | physical association | 0.400 | 1 | **BioGRID (56 interactions; top human partners by supporting records):** ASPSCR1 (Affinity Capture-MS; 2 records), BCOR (Affinity Capture-MS; 2 records), CTAGE5 (Affinity Capture-MS; 2 records), CYHR1 (Affinity Capture-MS; 2 records), EIF4G3 (Affinity Capture-MS; 2 records), GSE1 (Affinity Capture-MS; 2 records), HSPA8 (Affinity Capture-MS; 2 records), MIA3 (Affinity Capture-MS; 2 records), PM20D2 (Affinity Capture-MS; 2 records), PPFIBP1 (Affinity Capture-MS; 2 records), PPM1A (Affinity Capture-MS; 2 records), RBPMS (Affinity Capture-MS; 2 records), RBPMS2 (Affinity Capture-MS; 2 records), SF1 (Affinity Capture-MS; 2 records), SMG6 (Affinity Capture-MS; 2 records) ## Disease & clinical ### Genetic variants **Variant evidence for HAO2:** [60 ClinVar records](#clinvar) (0 pathogenic / likely pathogenic); [8 GWAS associations](#gwas-assoc). #### ClinVar 60 variants total. Per-class counts are floors (≥ shown; pagination cap): | Classification | Count (floor) | | --- | --- | | Pathogenic | 0 | | Likely pathogenic | 0 | | Uncertain significance | 51 | | Likely benign | 6 | | Benign | 0 | #### SpliceAI Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 840): | Position(s) | Effect | Δscore | Sites | | --- | --- | --- | --- | | 1:119385332 | donor_gain | 1.0000 | | | 1:119392219 | donor_gain | 1.0000 | | | 1:119382981 | donor_gain | 0.9900 | | | 1:119383886 | donor_gain | 0.9900 | | | 1:119384774–119384775 | acceptor_loss | 0.9900 | 6 | | 1:119385205 | donor_gain | 0.9900 | | | 1:119385364 | donor_gain | 0.9900 | | | 1:119381216–119381218 | donor_loss | 0.9800 | 7 | | 1:119382988 | donor_gain | 0.9800 | | | 1:119385054–119385055 | donor_loss | 0.9800 | 3 | #### AlphaMissense 628 missense substitutions predicted likely pathogenic (of 2,288 scored), across 200 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score: | Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity | | --- | --- | --- | --- | | D158 | 8 | 0.967 | 0.980 | | H246 | 8 | 0.958 | 0.973 | | D277 | 8 | 0.955 | 0.972 | | D229 | 8 | 0.885 | 0.956 | | D252 | 8 | 0.838 | 0.957 | | D285 | 8 | 0.790 | 0.897 | | D8 | 8 | 0.742 | 0.845 | | K222 | 7 | 0.940 | 0.998 | | W205 | 7 | 0.918 | 0.978 | | W126 | 7 | 0.898 | 0.992 | | E89 | 7 | 0.891 | 0.952 | | N38 | 7 | 0.870 | 0.980 | | S106 | 7 | 0.867 | 0.992 | | F42 | 7 | 0.866 | 0.932 | | F127 | 7 | 0.864 | 0.954 | | N245 | 7 | 0.864 | 0.984 | | W305 | 7 | 0.849 | 0.957 | | F24 | 7 | 0.840 | 0.963 | | Q128 | 7 | 0.821 | 0.922 | | G223 | 6 | 0.973 | 0.989 | ### HPA cancer prognostics **RNA cancer specificity:** Group enriched (Kidney Renal Clear Cell Carcinoma, Kidney Renal Papillary Cell Carcinoma, Liver Hepatocellular Carcinoma) Human Protein Atlas survival analysis — favorable = higher expression predicts better survival. 4 prognostic cancer types: | Cancer | Prognostic | p-value | | --- | --- | --- | | Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 1.43e-08 | | Kidney Renal Clear Cell Carcinoma (validation) | favorable | 5.51e-06 | | Liver Hepatocellular Carcinoma (validation) | favorable | 1e-05 | | Kidney Renal Papillary Cell Carcinoma (TCGA) | favorable | 0.000175 | ### Disease associations **OMIM:** gene `MIM:605176` | disease phenotypes: #### GWAS associations 8 associations: | Study | Trait | p-value | | --- | --- | --- | | GCST012020_309 | Serum metabolite levels | 5e-27 | | GCST012353_4 | Serum metabolite concentrations in chronic kidney disease | 4e-19 | | GCST012020_310 | Serum metabolite levels | 6e-17 | | GCST012353_5 | Serum metabolite concentrations in chronic kidney disease | 1e-14 | | GCST003996_8 | Monobrow | 4e-11 | | GCST008971_32 | Urate levels | 2e-8 | | GCST008972_148 | Urate levels | 2e-8 | | GCST007239_2 | Ovarian cancer | 8e-7 | #### EFO canonical traits (from GWAS) 2 canonical traits: | EFO ID | Trait name | | --- | --- | | EFO:0007906 | synophrys measurement | | EFO:0004531 | urate measurement | ## Drugs & pharmacology ### Drug and pharmacology data **Is drug target: yes** **ChEMBL targets (1):** CHEMBL2169732 (SINGLE PROTEIN) **PharmGKB:** 1 entry (CPIC guideline: no) #### Binding affinities (BindingDB) 1 measured of 1 human assays (1 total across all organisms); most potent 1 below. *Values come from heterogeneous assays and are not directly comparable.* | Ligand | Measure | Value | | --- | --- | --- | | CHEMBL2172058 | IC50 | 950 nM | #### ChEMBL bioactivities 1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM). | pChembl | Type | Value | Unit | Molecule | | --- | --- | --- | --- | --- | | 6.02 | IC50 | 950 | nM | [CHEMBL2172058](https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2172058/) | #### PubChem BioAssay actives 1 with measured affinity, of 107 total; 1 most potent distinct compounds. *Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.* | Compound | Assay | Type | Value | Unit | | --- | --- | --- | --- | --- | | 4-[3-(4-fluorophenyl)phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid | [702442](https://pubchem.ncbi.nlm.nih.gov/bioassay/702442/): Inhibition of human Hao2-mediated oxidation of 2-hydroxyoctanoic acid assessed as proportionate release of H2O2 | ic50 | 0.9500 | uM | #### CTD chemical–gene interactions 27 total (human), top 27 by PubMed support. | Chemical | Actions (top 5) | PubMed papers | | --- | --- | --- | | Tetrachlorodibenzodioxin | affects cotreatment, decreases expression, affects expression | 4 | | Benzo(a)pyrene | decreases expression, increases methylation | 3 | | Aflatoxin B1 | affects expression, decreases expression, decreases methylation | 3 | | perfluorooctane sulfonic acid | decreases expression | 2 | | Cyclosporine | decreases expression | 2 | | methyleugenol | decreases expression | 1 | | sodium arsenite | decreases expression | 1 | | perfluorooctanoic acid | decreases expression | 1 | | CGP 52608 | affects binding, increases reaction | 1 | | perfluoro-n-nonanoic acid | decreases expression | 1 | | Acetaminophen | decreases expression | 1 | | Arsenic | affects methylation | 1 | | Chenodeoxycholic Acid | affects cotreatment, decreases expression | 1 | | Deoxycholic Acid | affects cotreatment, decreases expression | 1 | | Endosulfan | affects cotreatment, decreases expression | 1 | | Estradiol | decreases expression | 1 | | Glycochenodeoxycholic Acid | affects cotreatment, decreases expression | 1 | | Glycocholic Acid | affects cotreatment, decreases expression | 1 | | Glycodeoxycholic Acid | affects cotreatment, decreases expression | 1 | | Methapyrilene | decreases expression | 1 | | Nickel | decreases expression | 1 | | Triclosan | affects cotreatment, decreases expression | 1 | | Valproic Acid | decreases expression | 1 | | Isotretinoin | decreases expression | 1 | | Cadmium Chloride | decreases expression | 1 | | Palmitic Acid | decreases expression | 1 | | Okadaic Acid | decreases expression | 1 | #### ChEMBL screening assays 3 unique, capped per target: 3 binding Representative assays (with source publication via chembl_document): | Assay ID | Type | Description | Source paper | | --- | --- | --- | --- | | CHEMBL2175908 | Binding | Inhibition of human Hao2-mediated oxidation of 2-hydroxyoctanoic acid assessed as proportionate release of H2O2 at 10 uM | Discovery of pyrazole carboxylic acids as potent inhibitors of rat long chain L-2-hydroxy acid oxidase. — \*Bioorg Med Chem Lett\* | #### Clinical trials (associated diseases) Via MONDO — disease-level, not drug-specific. #### Predicted chemistry — Sugi Predict The predicted patent-compound landscape for HAO2 across ~30M SureChEMBL compounds — [explore on Sugi Predict](https://sugi.bio/predict/target/HAO2/). ## Related Atlas pages *No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.*