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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPT2
glutamic--pyruvic transaminase 2
Chromosome 16 · 16q11.2
NCBI Gene: 84706Ensembl: ENSG00000166123.15HGNC: HGNC:18062UniProt: Q8TD30
53PubMed Papers
21Diseases
0Drugs
18Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
L-alanine:2-oxoglutarate transaminase activity2-oxoglutarate metabolic processGO:0042851mitochondrionglutamate pyruvate transaminase 2 deficiencyneurodegenerative diseasegenetic disorderlupus erythematosus
✦AI Summary

GPT2 (glutamic-pyruvic transaminase 2) is a mitochondrial enzyme that catalyzes the reversible transamination between alanine and α-ketoglutarate to form pyruvate and glutamate 1. Located in the mitochondrial matrix, GPT2 plays crucial roles in amino acid metabolism and cellular energy homeostasis. The enzyme facilitates glutamine catabolism, with its glutamate product serving as a precursor for GABA synthesis 1. GPT2 expression is regulated at multiple levels, including mRNA stability control by RNA-binding proteins like SPTBN1 2 and transcriptional activation through the Ku70-SIX1 complex 3. The enzyme demonstrates significant clinical relevance across multiple diseases. GPT2 is associated with neurodevelopmental disorders characterized by spastic paraplegia and microcephaly. In cancer, GPT2 promotes metastasis in breast cancer through GABA-GABAA receptor signaling and PKC-CREB pathway activation 1, while also facilitating tumor progression via exosomal mechanisms 4. Additionally, GPT2 contributes to metabolic reprogramming in renal clear cell carcinoma 2 and prostate cancer 3. In diabetes, GPT2 negatively regulates pancreatic β-cell incretin sensitivity, suggesting therapeutic potential in targeting GPT2 for improved glucose homeostasis 5. GPT2 also serves as a biomarker in atopic dermatitis, correlating with mitochondrial dysfunction 6.

Sources cited
1
GPT2 catalyzes transamination between alanine and α-ketoglutarate, produces glutamate for GABA synthesis, and promotes breast cancer metastasis via GABAA receptor signaling
PMID: 36923530
2
GPT2 mRNA stability is regulated by SPTBN1 and contributes to glycolysis reprogramming in renal clear cell carcinoma
PMID: 36527113
3
GPT2 is transcriptionally activated by Ku70-SIX1 complex and regulates α-ketoglutarate metabolism in prostate cancer
PMID: 39488663
4
Exosomal GPT2 from triple-negative breast cancer cells promotes metastasis by activating BTRC
PMID: 37287397
5
GPT2 negatively modulates pancreatic β-cell incretin response and represents a potential therapeutic target for type 2 diabetes
PMID: 40630539
6
GPT2 serves as a mitochondrial biomarker in atopic dermatitis and correlates with disease severity
PMID: 38774875
Disease Associationsⓘ21
glutamate pyruvate transaminase 2 deficiencyOpen Targets
0.77Strong
neurodegenerative diseaseOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.45Moderate
lupus erythematosusOpen Targets
0.31Weak
Intellectual disabilityOpen Targets
0.27Weak
hereditary spastic paraplegia 73Open Targets
0.27Weak
Rare genetic intellectual disabilityOpen Targets
0.26Weak
Neurodevelopmental disorderOpen Targets
0.11Weak
aggressive behaviorOpen Targets
0.11Weak
Delayed speech and language developmentOpen Targets
0.11Weak
Frequent fallsOpen Targets
0.11Weak
Mild intellectual disabilityOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
sarcopeniaOpen Targets
0.07Suggestive
obesityOpen Targets
0.04Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.04Suggestive
cancerOpen Targets
0.04Suggestive
Neurodevelopmental disorder with spastic paraplegia and microcephalyUniProt
Pathogenic Variants18
NM_133443.4(GPT2):c.22_35del (p.Val8fs)Pathogenic
Glutamate pyruvate transaminase 2 deficiency
★★☆☆2025→ Residue 8
NM_133443.4(GPT2):c.306del (p.Gln103fs)Pathogenic
Glutamate pyruvate transaminase 2 deficiency
★☆☆☆2024→ Residue 103
NM_133443.4(GPT2):c.333+2T>GLikely pathogenic
Glutamate pyruvate transaminase 2 deficiency
★☆☆☆2023
NM_133443.4(GPT2):c.924_925del (p.Pro309fs)Likely pathogenic
Glutamate pyruvate transaminase 2 deficiency
★☆☆☆2023→ Residue 309
NM_133443.4(GPT2):c.643C>T (p.Gln215Ter)Likely pathogenic
Glutamate pyruvate transaminase 2 deficiency
★☆☆☆2023→ Residue 215
NM_133443.4(GPT2):c.459C>G (p.Ser153Arg)Likely pathogenic
Glutamate pyruvate transaminase 2 deficiency|Inborn genetic diseases
★☆☆☆2023→ Residue 153
NM_133443.4(GPT2):c.1210C>T (p.Arg404Ter)Pathogenic
Glutamate pyruvate transaminase 2 deficiency|not provided
★☆☆☆2021→ Residue 404
NM_133443.4(GPT2):c.274C>T (p.Arg92Ter)Likely pathogenic
Glutamate pyruvate transaminase 2 deficiency
★☆☆☆2021→ Residue 92
NM_133443.4(GPT2):c.1133dup (p.Val379fs)Likely pathogenic
not provided
★☆☆☆2021→ Residue 379
NM_133443.4(GPT2):c.70C>T (p.Gln24Ter)Pathogenic
Inborn genetic diseases|Glutamate pyruvate transaminase 2 deficiency
★☆☆☆2017→ Residue 24
NM_133443.4(GPT2):c.181G>T (p.Glu61Ter)Pathogenic
not provided
★☆☆☆2016→ Residue 61
NM_133443.4(GPT2):c.58del (p.Trp20fs)Likely pathogenic
Glutamate pyruvate transaminase 2 deficiency
★☆☆☆→ Residue 20
NM_133443.4(GPT2):c.400C>T (p.Arg134Cys)Pathogenic
Glutamate pyruvate transaminase 2 deficiency
☆☆☆☆2020→ Residue 134
NM_133443.4(GPT2):c.1435G>A (p.Val479Met)Pathogenic
Glutamate pyruvate transaminase 2 deficiency
☆☆☆☆2020→ Residue 479
NM_133443.4(GPT2):c.1432_1433del (p.Val478fs)Pathogenic
Glutamate pyruvate transaminase 2 deficiency
☆☆☆☆2020→ Residue 478
NM_133443.4(GPT2):c.812A>C (p.Asn271Thr)Pathogenic
Glutamate pyruvate transaminase 2 deficiency
☆☆☆☆2020→ Residue 271
NM_133443.4(GPT2):c.1177dup (p.Val393fs)Likely pathogenic
Glutamate pyruvate transaminase 2 deficiency
☆☆☆☆2020→ Residue 393
NM_133443.4(GPT2):c.269del (p.Val90fs)Likely pathogenic
Rare genetic intellectual disability
☆☆☆☆→ Residue 90
View on ClinVar ↗
Related Genes
L2HGDHShared pathway100%ADHFE1Shared pathway100%GOT1Protein interaction98%SDHAProtein interaction98%PHGDHProtein interaction95%AGXTProtein interaction94%
Tissue Expression6 tissues
Liver
100%
Brain
39%
Heart
9%
Bone Marrow
8%
Ovary
2%
Lung
2%
Gene Interaction Network
Click a node to explore
GPT2L2HGDHADHFE1GOT1SDHAPHGDHAGXT
PROTEIN STRUCTURE
Preparing viewer…
PDB3IHJ · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.68LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.48 [0.35–0.68]
RankingsWhere GPT2 stands among ~20K protein-coding genes
  • #8,432of 20,598
    Most Researched53
  • #2,294of 5,498
    Most Pathogenic Variants18
  • #5,023of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedGPT2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The m
PMID: 36306790
Cancer Cell · 2022
1.00
2
Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma.
PMID: 35499760
Cancer Res · 2022
0.90
3
The delta subunit of the GABA
PMID: 36923530
Theranostics · 2023
0.80
4
Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning.
PMID: 38774875
Front Immunol · 2024
0.70
5
SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner.
PMID: 36527113
J Transl Med · 2022
0.60