FHIT Gene: Fragile Histidine Triad Diadenosine Triphosphatase
A tumor suppressor gene frequently altered in cancer, encoding a hydrolase involved in purine metabolism and apoptosis.
Gene Information Card
| Symbol | FHIT |
|---|---|
| Full Name | Fragile Histidine Triad Diadenosine Triphosphatase |
| Gene Type | Protein coding |
| Chromosomal Location | 3p14.2 |
| NCBI Gene ID | 2272 ncbi.nlm.nih.gov/gene/2272 |
| Ensembl ID | ENSG00000189283 |
| UniProt ID | P49789 |
| OMIM ID | 601153 |
| HGNC ID | 3701 |
| Aliases | AP3Aase, FRA3B, FHIT |
Description
The FHIT gene encodes a diadenosine triphosphatase (Ap3A hydrolase) involved in purine nucleotide metabolism. It spans the common fragile site FRA3B on chromosome 3p14.2, making it highly susceptible to deletions and rearrangements in cancer. FHIT functions as a tumor suppressor by regulating apoptosis, cell cycle, and DNA damage response. Loss of FHIT expression is frequently observed in various cancers, including lung, breast, esophageal, and gastric carcinomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lung cancer | Loss of FHIT expression due to deletions or promoter methylation leads to reduced apoptosis and increased genomic instability. | Multiple studies; COSMIC, ClinVar |
| Breast cancer | FHIT inactivation via loss of heterozygosity (LOH) at 3p14.2 contributes to tumor progression. | ClinVar, OMIM |
| Esophageal squamous cell carcinoma | Frequent FHIT deletions and reduced protein expression correlate with poor prognosis. | COSMIC, NCBI |
| Gastric cancer | Hypermethylation of FHIT promoter and allelic loss are common. | ClinVar, OMIM |
| Head and neck squamous cell carcinoma | FHIT loss associated with advanced stage and metastasis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Liver | 9.8 | Medium |
| Lung | 7.5 | Low |
| Breast | 6.2 | Low |
| Esophagus | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.5 | Embryonic kidney; high expression |
| HeLa | 8.2 | Cervical carcinoma; moderate |
| A549 | 4.3 | Lung carcinoma; low |
| MCF7 | 3.9 | Breast carcinoma; low |
| HCT116 | 6.7 | Colorectal carcinoma; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <1% | Loss of start codon; likely loss of function |
| c.244C>T (p.Arg82*) | Nonsense | <1% | Premature stop; loss of function |
| c.340_341del (p.Glu114fs) | Frameshift | <1% | Frameshift; loss of function |
| Exon 5 deletion | Deletion | Common in cancer | Loss of catalytic domain; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most FHIT mutations (nonsense, frameshift, deletions) result in loss of hydrolase activity and tumor suppressor function.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • diadenosine triphosphatase activity (GO:0003996) | • protein binding (GO:0005515) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • apoptotic process (GO:0006915) | • cell cycle (GO:0007049) |
| • nucleotide catabolic process (GO:0009166) |
Pathways
• Purine metabolism (KEGG: hsa00230)
• Apoptosis (Reactome: R-HSA-109581)
Protein Summary
FHIT is a 147-amino acid protein (17 kDa) that hydrolyzes diadenosine triphosphate (Ap3A) to AMP and ADP. It is predominantly cytoplasmic and plays a role in apoptosis and cell cycle regulation. Loss of FHIT protein expression is a hallmark of many cancers, often due to genomic deletions at the FRA3B fragile site.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FHIT Knockout HEK293 Cell Line | EDJ-KQ2877 | Human | 2272 | Details Get a Quote |
| FHIT Knockout HCT 116 Cell Line | EDJ-KQ23922 | Human | 2272 | Details Get a Quote |
| FHIT Knockout HeLa Cell Line | EDJ-KQ23923 | Human | 2272 | Details Get a Quote |
| FHIT Knockout A-549 Cell Line | EDJ-KQ61715 | Human | 2272 | Details Get a Quote |
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