HAAO

Chr 2AR

3-hydroxyanthranilate 3,4-dioxygenase

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

3-Hydroxyanthranilate 3,4-dioxygenase catalyzes the oxidative ring opening of 3-hydroxyanthranilate to produce quinolinate in the kynurenine pathway. Biallelic mutations cause vertebral, cardiac, renal, and limb defects syndrome 1, a multisystem developmental disorder with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
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.
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ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 52 VUS of 100 total submissions
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GeneReview available — HAAO
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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 OE0.74 (0.491.14)
00.351.4
Missense OE1.04 (0.921.18)
00.61.4
Synonymous OE1.13
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

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

100 submitted variants in ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic9
VUS52
Likely Benign5
Benign9
Conflicting1
17
Pathogenic
9
Likely Pathogenic
52
VUS
5
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
13
0
17
Likely Pathogenic
4
3
2
0
9
VUS
0
48
3
1
52
Likely Benign
0
3
1
1
5
Benign
0
3
4
2
9
Conflicting
1
Total75823493

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →