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6 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ETFBKMT
electron transfer flavoprotein subunit beta lysine methyltransferase
Chromosome 12 · 12p11.21
NCBI Gene: 254013Ensembl: ENSG00000139160.14HGNC: HGNC:28739UniProt: Q8IXQ9
17PubMed Papers
19Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-lysine N-methyltransferase activityheat shock protein bindingmitochondrionprotein-containing complextype 2 diabetes mellitusdiabetes mellitussmoking initiationmathematical ability
✦AI Summary

ETFBKMT (also known as METTL20) is a mitochondrial protein-lysine methyltransferase that selectively trimethylates lysine residues 199-203 in the β-subunit of electron transfer flavoprotein (ETFB) 12. This methylation occurs adjacent to the recognition loop of ETFB, a region critical for binding dehydrogenases involved in fatty acid oxidation and one-carbon metabolism 1. ETFBKMT-mediated methylation negatively regulates ETFB function by reducing its ability to accept electrons from acyl-CoA dehydrogenases, thus modulating electron transfer to the respiratory chain 2. Suppression of ETFBKMT-catalyzed ETFβ trimethylation decreases cellular oxygen consumption during fatty acid oxidation in mitochondria 1. Beyond metabolic function, ETFBKMT has emerged as a candidate gene associated with neurodevelopmental disorders; genomic deletions encompassing ETFBKMT have been identified in patients with intellectual disability and Kallmann syndrome, suggesting dosage-sensitive involvement in cognitive and neurological development 34. Additionally, ETFBKMT expression correlates with hepatic fibrosis progression, where it may contribute to reactive oxygen species production and fibrogenic signaling 5.

Sources cited
1
METTL20/ETFBKMT trimethylates lysine residues 199 and 202 in ETFβ in mitochondria, and suppression reduces oxygen consumption during fatty acid oxidation
PMID: 25023281
2
METTL20/ETFBKMT methylates ETFβ at Lys200 and Lys203, reducing its ability to receive electrons from acyl-CoA dehydrogenases
PMID: 25416781
3
ETFBKMT is identified as a candidate gene for neurodevelopmental disorder in patients with deletions at 12p11.21-12p11.23
PMID: 37563198
4
ETFBKMT dosage alterations may contribute to cognitive impairment in patients with intellectual disability and Kallmann syndrome
PMID: 37034680
5
ETFBKMT expression is reduced in liver fibrosis models and correlates with oxidoreductase activity
PMID: 37668531
Disease Associationsⓘ19
type 2 diabetes mellitusOpen Targets
0.28Weak
diabetes mellitusOpen Targets
0.27Weak
smoking initiationOpen Targets
0.09Suggestive
mathematical abilityOpen Targets
0.08Suggestive
diabetic ketoacidosisOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.00Suggestive
Neurodevelopmental disorderOpen Targets
0.00Suggestive
Neurodevelopmental delayOpen Targets
0.00Suggestive
Other metabolic diseaseOpen Targets
0.00Suggestive
acute myeloid leukemiaOpen Targets
0.00Suggestive
cervical cancerOpen Targets
0.00Suggestive
esophageal cancerOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
Hereditary breast cancerOpen Targets
0.00Suggestive
hereditary breast carcinomaOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
thyroid cancer, nonmedullary, 1Open Targets
0.00Suggestive
uterine corpus endometrial carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EEF1AKMT1Shared pathway100%EEF1AKMT2Protein interaction85%ETFBProtein interaction85%METTL22Protein interaction82%METTL21AProtein interaction82%EEF2KMTShared pathway50%
Tissue Expression6 tissues
Liver
100%
Heart
79%
Ovary
73%
Brain
58%
Lung
40%
Bone Marrow
16%
Gene Interaction Network
Click a node to explore
ETFBKMTEEF1AKMT1EEF1AKMT2ETFBMETTL22METTL21AEEF2KMT
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IXQ9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.68 [0.47–1.03]
RankingsWhere ETFBKMT stands among ~20K protein-coding genes
  • #14,992of 20,598
    Most Researched17
  • #10,127of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedETFBKMT
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Mediator subunit MED1 deficiency prevents carbon tetrachloride-induced hepatic fibrosis in mice.
PMID: 37668531
Am J Physiol Gastrointest Liver Physiol · 2023
1.00
2
A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.
PMID: 37563198
Sci Rep · 2023
0.83
3
A microdeletion del(12)(p11.21p11.23) with a cryptic unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.
PMID: 37034680
Res Sq · 2023
0.67
4
Human METTL20 is a mitochondrial lysine methyltransferase that targets the β subunit of electron transfer flavoprotein (ETFβ) and modulates its activity.
PMID: 25416781
J Biol Chem · 2015
0.50
5
Human METTL20 methylates lysine residues adjacent to the recognition loop of the electron transfer flavoprotein in mitochondria.
PMID: 25023281
J Biol Chem · 2014
0.33