HAAO

Chr 2AR

3-hydroxyanthranilate 3,4-dioxygenase

Also known as: 3-HAO, HAO, VCRL1, h3HAO

3-Hydroxyanthranilate 3,4-dioxygenase is a monomeric cytosolic protein belonging to the family of intramolecular dioxygenases containing nonheme ferrous iron. It is widely distributed in peripheral organs, such as liver and kidney, and is also present in low amounts in the central nervous system. HAAO catalyzes the synthesis of quinolinic acid (QUIN) from 3-hydroxyanthranilic acid. QUIN is an excitotoxin whose toxicity is mediated by its ability to activate glutamate N-methyl-D-aspartate receptors. Increased cerebral levels of QUIN may participate in the pathogenesis of neurologic and inflammatory disorders. HAAO has been suggested to play a role in disorders associated with altered tissue levels of QUIN. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 1.141 OMIM phenotype
Clinical SummaryHAAO
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Gene-Disease Validity (ClinGen)
vertebral, cardiac, renal, and limb defects syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.14LOEUF
pLI 0.000
Z-score 1.08
OE 0.74 (0.491.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.18Z-score
OE missense 1.04 (0.921.18)
167 obs / 160.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.74 (0.491.14)
00.351.4
Missense OE?1.04 (0.921.18)
00.61.4
Synonymous OE?1.13
01.21.6
LoF obs/exp: 15 / 20.2Missense obs/exp: 167 / 160.7Syn Z: -0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateHAAO-related NAD deficiency disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6743th %ile
GOF
0.5071th %ile
LOF
0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HAAO · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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