GPT
protein-codingglutamic--pyruvic transaminase
Gene summary
This gene encodes cytosolic alanine aminotransaminase 1 (ALT1); also known as glutamate-pyruvate transaminase 1. This enzyme catalyzes the reversible transamination between alanine and 2-oxoglutarate to generate pyruvate and glutamate and, therefore, plays a key role in the intermediary metabolism of glucose and amino acids. Serum activity levels of this enzyme are routinely used as a biomarker of liver injury caused by drug toxicity, infection, alcohol, and steatosis. A related gene on chromosome 16 encodes a putative mitochondrial alanine aminotransaminase.[provided by RefSeq, Nov 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005309.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 8 | 2 | 12 | ||
| missense | 84 | 12 | 3 | 99 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 93 | 20 | 5 | 118 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005300.1 | 11 | MANE Select | |
| Ensembl | ENSP00000378408.2 | 11 | MANE Select | |
| RefSeq | NP_001369593.1 | 11 | Standard | |
| RefSeq | NP_001369594.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
- Arginine biosynthesis - Homo sapiens (human)
- Pyruvate Carboxylase Deficiency
- Primary Hyperoxaluria Type I
- Argininemia
Biological Process
- cellular amino acid biosynthetic process
- L-alanine catabolic process
Molecular Function
- L-alanine:2-oxoglutarate aminotransferase activity
- pyridoxal phosphate binding
Cellular Component
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394955
- Coding exons
- 11
- Length
- 4202
- Individuals with no LoFs
- 125583
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 144
- Defined
- 125727
- p
- 0.000573
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.00 | 387 | 335 | 1.15 | 0.0000261 | 3161 |
| Missense (PolyPhen) | 170 | 136.41 | 1.2462 | 1329 | ||
| Synonymous | -3.62 | 205 | 149 | 1.38 | 0.0000124 | 1031 |
| Loss of Function | -0.757 | 26 | 22.2 | 1.17 | 0.00000106 | 240 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00025 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.000099 | 0.000092 | rare |
| European (Non-Finnish) | 0.00080 | 0.00073 | rare |
| South Asian | 0.00065 | 0.00065 | rare |
| Other | 0.00035 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with precursors transported from skeletal muscles (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.815
Intolerance Scores
- LoFtool
- 0.430
- RVIS EVS
- 0.29
- RVIS percentile EVS
- 71.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.230
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |