METTL21A Gene

Name methyltransferase like 21A
Description Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have expanded our understanding of protein methylation beyond classical epigenetic regulation. One investigation demonstrated that a novel methyltransferase associates preferentially with several molecular chaperones, catalyzing trimethylation on key lysine residues of substrates including VCP/p97, various Hsp70 isoforms, and KIN17. In this study, methylation of VCP proximal to its Walker B motif was shown to negatively impact its ATPase activity, an effect enhanced by the UBX cofactor ASPSCR1 and abolished by pathogenic VCP mutations linked to neuromuscular and neurodegenerative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSubsequently, METTL21A—also referred to as HSPA lysine methyltransferase (HSPA-KMT)—was identified as the enzyme that specifically trimethylates a conserved lysine residue present in several Hsp70 (HSPA) proteins. This methylation reaction, which is stimulated by ATP, appears highly selective for 70‐kDa chaperones and functionally impacts Hsp70 by altering its binding affinity for both monomeric and fibrillar forms of α-synuclein, a protein implicated in Parkinson disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings underscore the role of METTL21A and similar methyltransferases as pivotal regulators of chaperone function. By fine-tuning ATPase activity and modulating substrate interactions, METTL21A-mediated methylation emerges as an important post-translational mechanism for maintaining proteostasis and possibly influencing the pathogenesis of degenerative diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Philippe Cloutier, Mathieu Lavallée-Adam, Denis Faubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1003210"}], "href": "https://doi.org/10.1371/journal.pgen.1003210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23349634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23349634"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Magnus E Jakobsson, Anders Moen, Luc Bousset, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.483248"}], "href": "https://doi.org/10.1074/jbc.M113.483248"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23921388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23921388"}]}]}]}
Synonyms HSPA-KMT, FAM119A, HCA557B
Proteins MT21A_HUMAN
NCBI Gene ID 151194
API
Download Associations
Predicted Functions View METTL21A's ARCHS4 Predicted Functions.
Co-expressed Genes View METTL21A's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View METTL21A's ARCHS4 Predicted Functions.

Functional Associations

METTL21A has 4,340 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 90 datasets.

Click the + buttons to view associations for METTL21A from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of METTL21A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of METTL21A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of METTL21A gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of METTL21A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of METTL21A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of METTL21A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of METTL21A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of METTL21A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of METTL21A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with METTL21A gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of METTL21A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of METTL21A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of METTL21A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing METTL21A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing METTL21A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing METTL21A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with METTL21A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with METTL21A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with METTL21A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with METTL21A gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by METTL21A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with METTL21A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with METTL21A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with METTL21A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at METTL21A gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of METTL21A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of METTL21A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing METTL21A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with METTL21A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing METTL21A from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of METTL21A gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of METTL21A gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of METTL21A gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of METTL21A gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of METTL21A gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of METTL21A gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving METTL21A gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving METTL21A gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving METTL21A gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing METTL21A protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by METTL21A gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by METTL21A gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by METTL21A gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of METTL21A gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of METTL21A gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of METTL21A gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of METTL21A gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with METTL21A gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with METTL21A gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Disease Associations diseases associated with METTL21A gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with METTL21A gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of METTL21A gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of METTL21A gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of METTL21A protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of METTL21A gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for METTL21A protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of METTL21A gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of METTL21A gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of METTL21A gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of METTL21A gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of METTL21A gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with METTL21A gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain METTL21A protein from the LOCATE Predicted Protein Localization Annotations dataset.
MiRTarBase microRNA Targets microRNAs targeting METTL21A gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of METTL21A gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of METTL21A gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing METTL21A protein recovered by IP-MS from the NURSA Protein Complexes dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for METTL21A from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of METTL21A gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of METTL21A gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving METTL21A protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving METTL21A protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2024 pathways involving METTL21A protein from the Reactome Pathways 2024 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of METTL21A gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of METTL21A gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of METTL21A gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of METTL21A gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at METTL21A gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of METTL21A gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of METTL21A gene from the RummaGEO Gene Perturbation Signatures dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of METTL21A gene from the Sci-Plex Drug Perturbation Signatures dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of METTL21A gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of METTL21A gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of METTL21A gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of METTL21A gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of METTL21A protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of METTL21A protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of METTL21A protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of METTL21A protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with METTL21A protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.