GPT2

Chr 16AR

glutamic--pyruvic transaminase 2

Also known as: ALT2, GPT 2, MRT49, NEDSPM

NCBI Gene: 84706ENSG00000166123UniProt: Q8TD30OMIM: 138210

This mitochondrial alanine transaminase catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate, playing a key role in gluconeogenesis and amino acid metabolism across multiple tissues including skeletal muscle, kidney, and liver. Mutations cause neurodevelopmental disorder with microcephaly and spastic paraplegia with autosomal recessive inheritance. The gene is not highly constrained against loss-of-function variants (pLI 0.0003, LOEUF 0.698).

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.701 OMIM phenotype
Clinical Summary— GPT2
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Gene-Disease Validity (ClinGen)
glutamate pyruvate transaminase 2 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.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.000
Z-score 2.69
OE 0.41 (0.25–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.88Z-score
OE missense 0.70 (0.63–0.78)
216 obs / 308.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.25–0.70)
0≤0.351.4
Missense OE0.70 (0.63–0.78)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 10 / 24.3Missense obs/exp: 216 / 308.8Syn Z: 0.57
DN
0.6937th %ile
GOF
0.4678th %ile
LOF
0.3259th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GPT2 · 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

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.
Ouyang Q et al.·Proc Natl Acad Sci U S A
2016
Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy.
Yao Y et al.·Cancer Immunol Immunother
2025
Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo.
Baytas O et al.·Hum Mol Genet
2022Functional
Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning.
Yu H et al.·Front Immunol
2024Cohort
GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.
Hengel H et al.·Clin Genet
2018
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients