FTO Gene: Alpha-Ketoglutarate Dependent Dioxygenase
Genetic insights into FTO, its role in obesity, metabolism, and cancer risk.
Gene Information Card
| Symbol | FTO |
|---|---|
| Full Name | FTO alpha-ketoglutarate dependent dioxygenase |
| Gene Type | protein-coding |
| Chromosomal Location | 16q12.2 |
| NCBI Gene ID | 79068 ncbi.nlm.nih.gov/gene/79068 |
| Ensembl ID | ENSG00000140718 |
| UniProt ID | Q9C0B1 |
| OMIM ID | 610966 |
| HGNC ID | 24678 |
| Aliases | ALKBH9, MGC71164, KIAA1752 |
Description
The FTO gene encodes a member of the AlkB family of non-heme iron- and 2-oxoglutarate-dependent dioxygenases. It functions as a nucleic acid demethylase, specifically removing methyl groups from N6-methyladenosine (m6A) in RNA and 3-methylthymine in DNA. FTO is widely expressed, with highest levels in the brain, and is strongly associated with body mass index, obesity risk, and energy homeostasis. Variants in FTO have also been linked to various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | FTO intronic variants (e.g., rs9939609) affect expression in adipose tissue and hypothalamus, altering energy balance and appetite regulation. | Genome-wide association studies (GWAS) and meta-analyses; NCBI, OMIM |
| Type 2 Diabetes | Obesity-mediated risk; FTO variants increase BMI, indirectly elevating T2D susceptibility. | Large cohort studies; ClinVar, OMIM |
| Acute Myeloid Leukemia (AML) | FTO overexpression promotes leukemogenesis by reducing m6A levels on target mRNAs (e.g., MYC, CEBPA), enhancing oncogene expression. | Functional studies; COSMIC, PubMed |
| Breast Cancer | FTO expression correlates with tumor progression; demethylation of m6A on oncogenic transcripts. | Expression analysis; COSMIC, ClinVar |
| Melanoma | FTO variants associated with increased risk; potential role in UV-induced DNA damage repair. | GWAS; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 10.2 | High |
| Brain (cortex) | 9.8 | High |
| Adipose tissue | 7.5 | Medium |
| Liver | 6.1 | Medium |
| Pancreas | 5.3 | Medium |
| Skeletal muscle | 4.0 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.5 | High expression in embryonic kidney cells |
| HeLa | 10.1 | High expression in cervical cancer cells |
| K562 | 8.3 | Medium expression in leukemia cells |
| MCF7 | 7.0 | Medium expression in breast cancer cells |
| HepG2 | 6.2 | Medium expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs9939609 (T>A) | SNP (intronic) | ~40% (European) | Increased obesity risk; associated with higher FTO expression in adipose tissue |
| rs1421085 (T>C) | SNP (intronic) | ~30% (European) | Disrupts ARID5B repressor binding, leading to increased IRX3 and IRX5 expression, promoting adipogenesis and obesity |
| rs8050136 (A>C) | SNP (intronic) | ~38% (European) | Linked to obesity and T2D risk |
| R316Q | Missense | Rare | Reduced catalytic activity; associated with growth retardation and developmental delay |
| R96H | Missense | Rare | Loss of demethylase function; linked to severe obesity and intellectual disability |
Mutation functional classification
Loss of Function (LOF)
R316Q and R96H missense mutations reduce or abolish FTO demethylase activity, leading to altered RNA methylation and developmental phenotypes.
Gain of Function (GOF)
Overexpression of wild-type FTO (e.g., in AML) acts as a gain-of-function by decreasing m6A levels on oncogenic mRNAs, promoting cancer cell proliferation.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for FTO.
View complete mutation data：
Gene Ontology (GO)
| • mRNA N6-methyladenosine dioxygenase activity (GO:1990247) | • oxidative demethylation (GO:0070989) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
| • RNA binding (GO:0003723) | • iron ion binding (GO:0005506) |
| • 2-oxoglutarate-dependent dioxygenase activity (GO:0016706) |
Pathways
• m6A RNA methylation (Reactome: R-HSA-77588)
• Epigenetic regulation of gene expression (KEGG: hsa05200)
Protein Summary
FTO is a 505-amino acid protein (UniProt Q9C0B1) belonging to the AlkB family of dioxygenases. It localizes to the nucleus and cytoplasm and catalyzes the demethylation of N6-methyladenosine (m6A) in RNA, a key modification affecting RNA stability, splicing, and translation. The protein contains a conserved double-stranded β-helix (DSBH) fold and requires Fe(II) and 2-oxoglutarate as cofactors. FTO is highly expressed in the brain and plays a critical role in energy metabolism, adipogenesis, and cancer biology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FTO Knockout HEK293 Cell Line | EDJ-KQ187 | Human | 79068 | Details Get a Quote |
| FTO Knockout HeLa Cell Line | EDJ-KQ19015 | Human | 79068 | Details Get a Quote |
| FTO Knockout A-549 Cell Line | EDJ-KQ20359 | Human | 79068 | Details Get a Quote |
| FTO Knockout HCT 116 Cell Line | EDC90280 | Human | 79068 | Details Get a Quote |
| FTO Knockout MAC-T Cell Line | EDC07933 | Bovine | 618622 | Details Get a Quote |
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