AlphaFold predicted structure
FTO · Q9C0B1
Mean pLDDT
91.0/ 100
Very high
505 residues
Confidence breakdown
- Very high(≥ 90)80%
- Confident(70–90)12%
- Low(50–70)4%
- Very low(< 50)5%
Open interactive 3D viewer
AlphaFold (Jumper et al., 2021) · CC BY 4.0
FTO
Chr 16q12.2FTO alpha-ketoglutarate dependent dioxygenase
- Aliases:
- KIAA1752, MGC5149, ALKBH9, IFEX9
- MANE:
- ENST00000471389.6
Annotations refreshed 12 hours ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomalClefting
BIALLELIC, autosomal or pseudoautosomalIntellectual disability
BIALLELIC, autosomal or pseudoautosomalDDG2P
BIALLELIC, autosomal or pseudoautosomalRare syndromic craniosynostosis or isolated multisuture synostosis
BIALLELIC, autosomal or pseudoautosomal
Disease associations (Open Targets)
lethal polymalformative syndrome, Boissel type
0.71obesity disorder
0.69type 2 diabetes mellitus
0.62diabetes mellitus
0.61breast carcinoma
0.59hypertensive disorder
0.59atrial fibrillation
0.59heart failure
0.58breast cancer
0.58osteoarthritis
0.58
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Alpha-ketoglutarate-dependent dioxygenase FTO
RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:28002401, PubMed:30197295). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:30197295). M6A demethylation by FTO affects mRNA expression and stability (PubMed:30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:30197295). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:30197295). Has no activity towards 1-methylguanine (PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:18775698, PubMed:20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:28017614, PubMed:29249359)
Diseases associated with FTO
Curated MONDO disease pages that list FTO among their top associated genes.