Seroatlas · Human Serome Atlas

FTO

Alpha-ketoglutarate-dependent dioxygenase FTO

Also known as: ALKBH9, FTO_HUMAN, KIAA1752, MGC5149

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9C0B1
Gene: FTO
Ensembl: ENSG00000140718
Chromosome: 16
Canonical length: 505 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
Subcellular location: Vesicles,Cytosol
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

Canonical amino-acid sequenceUniProt

505 residues, UniProt reviewed canonical sequence.

>Q9C0B1|FTO
     1  MKRTPTAEER EREAKKLRLL EELEDTWLPY LTPKDDEFYQ QWQLKYPKLI LREASSVSEE
    61  LHKEVQEAFL TLHKHGCLFR DLVRIQGKDL LTPVSRILIG NPGCTYKYLN TRLFTVPWPV
   121  KGSNIKHTEA EIAAACETFL KLNDYLQIET IQALEELAAK EKANEDAVPL CMSADFPRVG
   181  MGSSYNGQDE VDIKSRAAYN VTLLNFMDPQ KMPYLKEEPY FGMGKMAVSW HHDENLVDRS
   241  AVAVYSYSCE GPEEESEDDS HLEGRDPDIW HVGFKISWDI ETPGLAIPLH QGDCYFMLDD
   301  LNATHQHCVL AGSQPRFSST HRVAECSTGT LDYILQRCQL ALQNVCDDVD NDDVSLKSFE
   361  PAVLKQGEEI HNEVEFEWLR QFWFQGNRYR KCTDWWCQPM AQLEALWKKM EGVTNAVLHE
   421  VKREGLPVEQ RNEILTAILA SLTARQNLRR EWHARCQSRI ARTLPADQKP ECRPYWEKDD
   481  ASMPLPFDLT DIVSELRGQL LEAKP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FTO can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.27
Highest tissue expression: 44 nTPM

Expression across tissuesHPA

Tissue

basal ganglia: 44 nTPM
cerebral cortex: 43 nTPM
hypothalamus: 40 nTPM
parathyroid gland: 38 nTPM
cerebellum: 37 nTPM
retina: 35 nTPM

Single-cell type

respiratory ciliated cells: 2,048 nCPM
choroid plexus epithelial cells: 663 nCPM
lactotrophs: 590 nCPM
somatotrophs: 583 nCPM
thyrotrophs: 548 nCPM
adrenal cortex cells: 523 nCPM

Immune cell

MAIT T-cell: 32 nTPM
T-reg: 27 nTPM
NK-cell: 27 nTPM
memory CD8 T-cell: 26 nTPM
gdT-cell: 26 nTPM
memory CD4 T-cell: 24 nTPM

Brain region

white matter: 113 nTPM
hypothalamus: 108 nTPM
basal ganglia: 102 nTPM
cerebral cortex: 98 nTPM
pons: 95 nTPM
midbrain: 94 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FTO.

Disease | AllUniProt

Conditions FTO is implicated in, by any mechanism.

Growth retardation, developmental delay, and facial dysmorphism (GDFD) MIM:612938
Obesity (OBESITY) MIM:601665

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 279 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Lethal polymalformative syndrome, Boissel type
Body mass index quantitative trait locus 14

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.85
gnomAD pLI: 0
gnomAD missense Z: 0.56
DepMap mean gene effect: -0.06
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

adipose tissue development
DNA alkylation repair
mRNA destabilization
regulation of brown fat cell differentiation
regulation of lipid storage
regulation of multicellular organism growth
regulation of respiratory system process
RNA repair
snRNA processing
temperature homeostasis
regulation of white fat cell proliferation

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily
Alpha-ketoglutarate-dependent dioxygenase FTO, C-terminal
Alpha-ketoglutarate-dependent dioxygenase FTO, catalytic domain
Alpha-ketoglutarate-dependent dioxygenase FTO
FTO, C-terminal domain superfamily
FTO catalytic domain
FTO C-terminal domain

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads FTO as an antibody target. Whether an autoantibody or antibody against FTO could matter depends on whether native FTO is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

FTO is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label FTO as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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