GOT2

Chr 16AR

glutamic-oxaloacetic transaminase 2

Also known as: DEE82, KAT4, KATIV, KYAT4, mitAAT

NCBI Gene: 2806 ENSG00000125166 UniProt: P00505 OMIM: 138150

Glutamic-oxaloacetic transaminase 2 (GOT2) is a mitochondrial enzyme that catalyzes amino acid transamination reactions, plays a key role in the malate-aspartate shuttle for intracellular NAD(H) redox balance, and facilitates cellular uptake of long-chain fatty acids. Biallelic mutations cause developmental and epileptic encephalopathy 82, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.623), affecting both neurological development and seizure control.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles. The two enzymes are homodimeric and show close homology. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 82MIM #618721

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · mitochondrial disease · AR · ClinGen 2025

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.014

Z-score 2.84

OE 0.33 (0.19–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.39Z-score

OE missense 0.75 (0.67–0.85)

190 obs / 251.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.19–0.62)

0≤0.351.4

Missense OE?0.75 (0.67–0.85)

0≤0.61.4

Synonymous OE?0.74

0≤1.21.6

LoF obs/exp: 7 / 21.1Missense obs/exp: 190 / 251.9Syn Z: 1.93

Background carrier burden — how many people carry a rare variant somewhere in GOT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

465 rare PASS variants

Rare truncating (LoF)

1 in 4,700

47 rare PASS variants

Rare synonymous (reference)

1 in 220

184 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GOT2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 5,700
South Asian	~43k	1 in 100	1 in 980
Remaining (unassigned)	~30k	1 in 92	≈ 1 in 30,000
European (Finnish)	~27k	1 in 790	≈ 1 in 7,700
Admixed American	~22k	1 in 160	≈ 1 in 7,700
African / African American	~21k	1 in 95	1 in 3,000
East Asian	~20k	1 in 120	none seen
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓