GART
protein-codingphosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase, the group of Purinosome
Gene summary
The protein encoded by this gene is a trifunctional polypeptide. It has phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase activity which is required for de novo purine biosynthesis. This enzyme is highly conserved in vertebrates. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
- PRGS
- PGFT
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.6 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 GART variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000819.5. 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 | 2 | ||||
| missense | 1 | 109 | 5 | 115 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 115 | 5 | 0 | 121 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000810.1 | 21 | MANE Select | |
| Ensembl | ENSP00000371236.4 | 21 | MANE Select | |
| RefSeq | NP_001129477.1 | 21 | Standard | |
| RefSeq | NP_001129478.1 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gart | Danio rerio | Structure: iridophore Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
- One carbon pool by folate - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Methotrexate Pathway (Cancer Cell), Pharmacodynamics
- Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics
Biological Process
- brainstem development
- purine nucleotide biosynthetic process
- 'de novo' IMP biosynthetic process
- glycine metabolic process
- purine ribonucleoside monophosphate biosynthetic process
Molecular Function
- phosphoribosylamine-glycine ligase activity
- phosphoribosylformylglycinamidine cyclo-ligase activity
- phosphoribosylglycinamide formyltransferase activity
- ATP binding
- metal ion binding
Cellular Component
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381831
- Coding exons
- 21
- Length
- 39560
- Individuals with no LoFs
- 125693
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 54
- Defined
- 125747
- p
- 0.000215
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.11 | 461 | 533 | 0.865 | 0.0000263 | 6532 |
| Missense (PolyPhen) | 142 | 202.23 | 0.70217 | 2494 | ||
| Synonymous | 0.0509 | 193 | 194 | 0.995 | 0.00000997 | 2060 |
| Loss of Function | 4.22 | 15 | 45.8 | 0.328 | 0.00000221 | 589 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.456
Intolerance Scores
- LoFtool
- 0.823
- RVIS EVS
- 0.74
- RVIS percentile EVS
- 86.34
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |