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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TKFC
triokinase and FMN cyclase
Chromosome 11 Β· 11q12.2
NCBI Gene: 26007Ensembl: ENSG00000149476.17HGNC: HGNC:24552UniProt: A0A140VJH7
49PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
glycerone kinase activityprotein bindingcarbohydrate metabolic processnegative regulation of MDA-5 signaling pathwaytriokinase and FMN cyclase deficiency syndromeSengers syndromeCOVID-19Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathy
✦AI Summary

TKFC (triokinase and FMN cyclase) encodes a bifunctional enzyme with dual catalytic activities: triokinase activity that phosphorylates glyceraldehyde and dihydroxyacetone in fructose metabolism, and FMN cyclase activity that cleaves FAD to generate cyclic FMN 1. The enzyme plays a crucial role in fructose metabolism, where triokinase activity converts glyceraldehyde to glyceraldehyde-3-phosphate, favoring lipogenesis over fructose oxidation 2. TKFC expression is regulated by metabolic transcription factors ChR11 and HNF4Ξ±, with refeeding inducing hepatic expression 3. The protein forms dimeric structures with two active sites that undergo conformational changes during substrate binding and catalysis 4. TKFC deficiency causes a rare multisystem disorder characterized by cataracts, developmental delay, cerebellar hypoplasia, liver dysfunction, and potentially fatal cardiomyopathy 15. The disease mechanism likely involves disrupted fructose metabolism leading to toxic by-product accumulation and cataract formation. Additionally, TKFC may regulate innate antiviral immunity through MDA5 pathway suppression, potentially explaining severe viral illness susceptibility in deficient patients 1. Alternative splicing generates tissue-specific TKFC variants with differential expression patterns across organs 6.

Sources cited
1
TKFC is a bifunctional enzyme with triokinase and FMN cyclase activities, and deficiency causes cataracts, developmental delay, and multisystem disease
PMID: 32004446
2
Triokinase activity phosphorylates glyceraldehyde in fructose metabolism and favors lipogenesis over fructose oxidation
PMID: 35114011
3
TKFC expression is regulated by ChREBP and HNF4Ξ± transcription factors and induced by refeeding
PMID: 38782732
4
TKFC forms dimeric structures with conformational changes during substrate binding and catalysis
PMID: 30836629
5
TKFC deficiency can cause severe skeletal abnormalities and lethal hypertrophic cardiomyopathy
PMID: 39251934
6
Alternative splicing generates tissue-specific TKFC variants with differential expression patterns
PMID: 39456221
Disease Associationsβ“˜21
triokinase and FMN cyclase deficiency syndromeOpen Targets
0.63Moderate
Sengers syndromeOpen Targets
0.40Weak
COVID-19Open Targets
0.37Weak
Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathyOpen Targets
0.37Weak
inborn errors of metabolismOpen Targets
0.33Weak
Autosomal recessive malignant osteopetrosisOpen Targets
0.04Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.03Suggestive
idiopathic hypereosinophilic syndromeOpen Targets
0.03Suggestive
dominant beta-thalassemiaOpen Targets
0.03Suggestive
hemoglobin H diseaseOpen Targets
0.03Suggestive
autosomal recessive osteopetrosis 4Open Targets
0.03Suggestive
acute erythroleukemiaOpen Targets
0.03Suggestive
erythroleukemia, familial, susceptibility toOpen Targets
0.03Suggestive
retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeOpen Targets
0.03Suggestive
adrenal cortex carcinomaOpen Targets
0.02Suggestive
Crohn's diseaseOpen Targets
0.02Suggestive
cataractOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
gliomaOpen Targets
0.01Suggestive
glioblastoma multiformeOpen Targets
0.01Suggestive
Triokinase and FMN cyclase deficiency syndromeUniProt
Pathogenic Variants2
NM_015533.4(TKFC):c.1628G>T (p.Arg543Ile)Likely pathogenic
TKFC deficiency;Inborn errors of metabolism|Triokinase and FMN cyclase deficiency syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 543
NM_015533.4(TKFC):c.1333G>A (p.Gly445Ser)Likely pathogenic
Triokinase and FMN cyclase deficiency syndrome|TKFC deficiency;Inborn errors of metabolism
β˜…β˜†β˜†β˜†2020β†’ Residue 445
View on ClinVar β†—
Related Genes
ALDOAProtein interaction99%ALDOBProtein interaction99%ALDOCProtein interaction99%TPI1Protein interaction99%IFIH1Protein interaction96%GLYCTKProtein interaction86%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
22%
Ovary
17%
Brain
14%
Lung
13%
Heart
10%
Gene Interaction Network
Click a node to explore
TKFCALDOAALDOBALDOCTPI1IFIH1GLYCTK
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q3LXA3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.75 [0.59–0.97]
RankingsWhere TKFC stands among ~20K protein-coding genes
  • #9,026of 20,598
    Most Researched49
  • #4,441of 5,498
    Most Pathogenic Variants2
  • #9,185of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedTKFC
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Molecular aspects of fructose metabolism and metabolic disease.
PMID: 34619074
Cell Metab Β· 2021
1.00
2
Alternative Splicing of the Last
PMID: 39456221
Biomolecules Β· 2024
0.90
3
Biallelic TYR and TKFC variants in Egyptian patients with OCA1 and new expanded TKFC features.
PMID: 39251934
BMC Genomics Β· 2024
0.80
4
Integrative computational modeling to unravel novel potential biomarkers in hepatocellular carcinoma.
PMID: 37116239
Comput Biol Med Β· 2023
0.70
5
Closure of the Human TKFC Active Site: Comparison of the Apoenzyme and the Complexes Formed with Either Triokinase or FMN Cyclase Substrates.
PMID: 30836629
Int J Mol Sci Β· 2019
0.60