OAT

Chr 10

ornithine aminotransferase

Also known as: GACR, HOGA, OATASE, OKT

NCBI Gene: 4942 ENSG00000065154 UniProt: P04181

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the mitochondrial enzyme ornithine aminotransferase, which is a key enzyme in the pathway that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Mutations that result in a deficiency of this enzyme cause the autosomal recessive eye disease Gyrate Atrophy. Alternatively spliced transcript variants encoding different isoforms have been described. Related pseudogenes have been defined on the X chromosome. [provided by RefSeq, Jan 2010]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.96

Clinical Summary— OAT

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Gene-Disease Validity (ClinGen)

ornithine aminotransferase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

159 unique Pathogenic / Likely Pathogenic· 214 VUS of 743 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — OAT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.70

OE 0.61 (0.39–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.88Z-score

OE missense 0.84 (0.75–0.94)

204 obs / 242.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.39–0.96)

0≤0.351.4

Missense OE?0.84 (0.75–0.94)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

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

This gene — mechanism propensity

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

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

743 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59

Likely Pathogenic100

VUS214

Likely Benign288

Benign57

Conflicting21

Pathogenic

100

Likely Pathogenic

214

VUS

288

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	37	14	8	0	59
Likely Pathogenic	68	29	3	0	100
VUS	2	179	28	5	214
Likely Benign	0	4	109	175	288
Benign	0	1	55	1	57
Conflicting	—				21
Total	107	227	203	181	739

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap OAT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →