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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HEMK1
HemK methyltransferase 1, mitochondrial release factors N(5)-glutamine
Chromosome 3 · 3p21.31
NCBI Gene: 51409Ensembl: ENSG00000114735.11HGNC: HGNC:24923UniProt: A0A140VK98
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpeptide chain release factor N(5)-glutamine methyltransferase activitymitochondrionprotein-glutamine N-methyltransferase activityAbnormality of the skeletal systemanxiety disorderdepressive disordermajor depressive disorder
✦AI Summary

HEMK1 is an N5-glutamine methyltransferase that catalyzes methylation of the highly conserved GGQ motif in mitochondrial translation release factors (mtRFs), including MTRF1, MTRF1L, MRPL58, and MTRFR 1. This modification mirrors the bacterial PrmC enzyme's function in prokaryotic release factors and represents a conserved post-translational modification across prokaryotes and eukaryotes 1. Mechanistically, HEMK1-mediated GGQ methylation occurs in all four human mtRFs, as demonstrated by the absence of this modification in HEMK1-knockout cells 1. Despite its specific enzymatic activity, disruption of HEMK1 had minimal impact on cell growth, mitochondrial DNA copy number, membrane potential, and mitochondrial protein synthesis in HeLa cells under standard culture conditions, suggesting this modification is largely dispensable for basal cellular function 1. HEMK1 has been identified as a co-expressed gene associated with FHIT in lung adenocarcinoma 2 and as a hub gene in coronary artery disease pathogenesis networks 3. Additionally, HEMK1 expression is upregulated in allergen-specific T cells from peanut-allergic patients and appears in disease-relevant genetic networks for type 1 and 2 diabetes 4 5. These associations suggest potential roles beyond mitochondrial translation termination, though clinical significance remains to be fully elucidated.

Sources cited
1
HEMK1 methylates glutamine in the GGQ motif of mitochondrial release factors; this modification is absent in HEMK1-deficient cells but is dispensable for cell growth and mitochondrial function under normal conditions
PMID: 35260756
2
HEMK1 is identified as a gene with strongest correlation to FHIT expression in lung adenocarcinoma patients
PMID: 35254116
3
HEMK1 is a hub gene in protein-protein interaction networks associated with coronary artery disease pathogenesis
PMID: 31881747
4
HEMK1 expression is significantly upregulated in allergen-specific T cells from peanut-allergic patients
PMID: 30893695
5
HEMK1 is identified as a common gene in T1D and T2D loci that harbors islet eQTLs linked to disease-associated variants
PMID: 33777101
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.21Weak
anxiety disorderOpen Targets
0.05Suggestive
depressive disorderOpen Targets
0.05Suggestive
major depressive disorderOpen Targets
0.03Suggestive
mood disorderOpen Targets
0.03Suggestive
schizophreniaOpen Targets
0.03Suggestive
mathematical abilityOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.02Suggestive
obesityOpen Targets
0.02Suggestive
radiculitisOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
mental or behavioural disorderOpen Targets
0.02Suggestive
infectionOpen Targets
0.01Suggestive
gonorrheaOpen Targets
0.00Suggestive
bacteriemiaOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
type 1 diabetes mellitusOpen Targets
0.00Suggestive
type 2 diabetes mellitusOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
parasitic infectionOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRMT112Protein interaction100%CPOXProtein interaction82%FECHProtein interaction82%NAMPTProtein interaction78%FBXO5Protein interaction78%HEMK2Protein interaction78%
Tissue Expression6 tissues
Ovary
100%
Liver
86%
Lung
42%
Heart
33%
Bone Marrow
28%
Brain
9%
Gene Interaction Network
Click a node to explore
HEMK1TRMT112CPOXFECHNAMPTFBXO5HEMK2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9Y5R4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.96LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.54–0.96]
RankingsWhere HEMK1 stands among ~20K protein-coding genes
  • #14,712of 20,598
    Most Researched18
  • #9,025of 17,882
    Most Constrained (LOEUF)0.96
Genes detectedHEMK1
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Mammalian HEMK1 methylates glutamine residue of the GGQ motif of mitochondrial release factors.
PMID: 35260756
Sci Rep · 2022
1.00
2
In silico analysis of microRNA genes in azoospermia factor Y-chromosome microdeletions.
PMID: 35124761
Int Urol Nephrol · 2022
0.86
3
System analysis of
PMID: 35254116
Int J Biol Markers · 2022
0.71
4
Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis.
PMID: 31881747
Biomolecules · 2019
0.57
5
Saethre-Chotzen phenotype with learning disability and hyper IgE phenotype in a patient due to complex chromosomal rearrangement involving chromosomes 3 and 7.
PMID: 22628249
Am J Med Genet A · 2012
0.43