ATIC Gene - 5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase
Comprehensive genomic and proteomic analysis of ATIC, a bifunctional enzyme in purine biosynthesis.
Gene Information Card
| Symbol | ATIC |
|---|---|
| Full Name | 5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 471 ncbi.nlm.nih.gov/gene/471 |
| Ensembl ID | ENSG00000138363 |
| UniProt ID | P31939 |
| OMIM ID | 601731 |
| HGNC ID | 794 |
| Aliases | AICARFT, IMPCHASE, PURH |
Description
The ATIC gene encodes a bifunctional enzyme that catalyzes the final two steps of de novo purine biosynthesis: 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT) and inosine monophosphate cyclohydrolase (IMPCH). This enzyme converts AICAR to FAICAR and then to IMP, a precursor for adenine and guanine nucleotides. Mutations in ATIC cause AICA-ribosiduria, a rare autosomal recessive disorder, and altered expression is implicated in cancer and response to antifolate drugs.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| AICA-ribosiduria | Loss-of-function mutations in ATIC impair purine synthesis, leading to accumulation of AICAR and neurological symptoms. | OMIM #608688; ClinVar |
| Colorectal cancer | ATIC overexpression may promote purine synthesis and tumor growth; gene amplification observed. | COSMIC; NCBI PubMed |
| Breast cancer | ATIC expression correlates with poor prognosis and resistance to methotrexate. | NCBI PubMed; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Brain | 4.1 | Low |
| Heart | 3.8 | Low |
| Lung | 6.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| HEK293 | 10.8 | Moderate expression |
| MCF7 | 7.5 | Moderate expression |
| A549 | 9.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.742C>T (p.Arg248*) | Nonsense | Rare | Loss of function; associated with AICA-ribosiduria |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; associated with AICA-ribosiduria |
| c.1057G>A (p.Val353Met) | Missense | <0.01% | Unknown significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations cause complete loss of enzyme activity, leading to AICA-ribosiduria.
Gain of Function (GOF)
Not reported; no activating mutations described in literature.
Dominant Negative (DN)
Not reported; no dominant-negative variants known.
View complete mutation data：
Gene Ontology (GO)
| • AICARFT activity (GO:0004641) | • IMP cyclohydrolase activity (GO:0004643) |
| • de novo' IMP biosynthetic process (GO:0006189) | • cytoplasm (GO:0005737) |
Pathways
• De novo purine biosynthesis (Reactome: R-HSA-73817)
• Metabolism of nucleotides (KEGG: hsa00230)
Protein Summary
The ATIC protein (P31939) is a bifunctional 64 kDa enzyme that catalyzes the last two steps of de novo purine biosynthesis. It contains an N-terminal AICARFT domain and a C-terminal IMPCH domain. The protein is expressed in most tissues, with highest levels in liver and kidney. It is a target for antifolate drugs such as methotrexate and pemetrexed.
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