OAT

Chr 10AR

ornithine aminotransferase

Also known as: GACR, HOGA, OATASE, OKT

The mitochondrial enzyme ornithine aminotransferase catalyzes the reversible interconversion of L-ornithine and 2-oxoglutarate to L-glutamate semialdehyde and L-glutamate, serving as a key enzyme in the pathway converting arginine and ornithine into the neurotransmitters glutamate and GABA. Mutations cause gyrate atrophy of choroid and retina with or without ornithinemia, an autosomal recessive eye disease that primarily affects the posterior segment of the eye. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its autosomal recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.961 OMIM phenotype
Clinical SummaryOAT
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Gene-Disease Validity (ClinGen)
ornithine aminotransferase deficiency · 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
89 unique Pathogenic / Likely Pathogenic· 145 VUS of 500 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — OAT
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

opentargets: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.000
Z-score 1.70
OE 0.61 (0.390.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.88Z-score
OE missense 0.84 (0.750.94)
204 obs / 242.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.390.96)
00.351.4
Missense OE0.84 (0.750.94)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 13 / 21.5Missense obs/exp: 204 / 242.4Syn Z: 1.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveOAT-related gyrate atrophy of choroid and retina with or without ornithinemiaLOFAR

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

DN
0.7327th %ile
GOF
0.6442th %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

500 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic52
VUS145
Likely Benign256
Benign3
Conflicting3
37
Pathogenic
52
Likely Pathogenic
145
VUS
256
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
1
19
0
37
Likely Pathogenic
44
5
3
0
52
VUS
2
132
7
4
145
Likely Benign
0
3
96
157
256
Benign
0
0
3
0
3
Conflicting
3
Total63141128161496

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

View in ClinVar →

Protein Context — Lollipop Plot

OAT · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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