METTL4
N(6)-adenine-specific methyltransferase METTL4
Also known as: FLJ23017, HsT661, METL4_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q8N3J2
- Gene
- METTL4
- Ensembl
- ENSG00000101574
- Chromosome
- 18
- Canonical length
- 472 aa
- Protein class
- Enzymes, Predicted intracellular proteins
- Subcellular location
- Mitochondria
OverviewNCBI Gene
Enables RNA methyltransferase activity and site-specific DNA-methyltransferase (adenine-specific) activity. Involved in regulation of primary metabolic process and snRNA (adenine-N6)-methylation. Located in cytosol; mitochondrial matrix; and nucleus. Part of RNA N6-methyladenosine methyltransferase complex and oxidoreductase complex. [provided by Alliance of Genome Resources, Jul 2025]
Canonical amino-acid sequenceUniProt
472 residues, UniProt reviewed canonical sequence.
>Q8N3J2|METTL4
1 MSVVHQLSAG WLLDHLSFIN KINYQLHQHH EPCCRKKEFT TSVHFESLQM DSVSSSGVCA
61 AFIASDSSTK PENDDGGNYE MFTRKFVFRP ELFDVTKPYI TPAVHKECQQ SNEKEDLMNG
121 VKKEISISII GKKRKRCVVF NQGELDAMEY HTKIRELILD GSLQLIQEGL KSGFLYPLFE
181 KQDKGSKPIT LPLDACSLSE LCEMAKHLPS LNEMEHQTLQ LVEEDTSVTE QDLFLRVVEN
241 NSSFTKVITL MGQKYLLPPK SSFLLSDISC MQPLLNYRKT FDVIVIDPPW QNKSVKRSNR
301 YSYLSPLQIQ QIPIPKLAAP NCLLVTWVTN RQKHLRFIKE ELYPSWSVEV VAEWHWVKIT
361 NSGEFVFPLD SPHKKPYEGL ILGRVQEKTA LPLRNADVNV LPIPDHKLIV SVPCTLHSHK
421 PPLAEVLKDY IKPDGEYLEL FARNLQPGWT SWGNEVLKFQ HVDYFIAVES GSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against METTL4 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)
- 0.34
- Highest tissue expression
- 11 nTPM
Expression across tissuesHPA
Tissue
- lymph node: 11 nTPM
- tonsil: 10 nTPM
- thymus: 9.7 nTPM
- thyroid gland: 8.3 nTPM
- spleen: 7.7 nTPM
- appendix: 7.4 nTPM
Single-cell type
- pituicytes/fscs: 37 nCPM
- early primary spermatocytes: 37 nCPM
- b-cells: 35 nCPM
- oligodendrocytes: 31 nCPM
- t-cells: 31 nCPM
- lymphatic endothelial cells: 31 nCPM
Immune cell
- basophil: 19 nTPM
- neutrophil: 10 nTPM
- T-reg: 8.8 nTPM
- memory CD8 T-cell: 8.5 nTPM
- naive CD4 T-cell: 8.5 nTPM
- naive CD8 T-cell: 7.9 nTPM
Brain region
- white matter: 13 nTPM
- pons: 11 nTPM
- medulla oblongata: 11 nTPM
- cerebral cortex: 11 nTPM
- spinal cord: 10 nTPM
- basal ganglia: 9.8 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about METTL4.
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 72 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
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)
- 0.95
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.39
- DepMap mean gene effect
- 0.09
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- methylation
- negative regulation of gene expression, epigenetic
- regulation of mitochondrial transcription
- regulation of RNA splicing
- snRNA (adenine-N6)-methylation
- regulation of mitochondrial DNA replication
Molecular functions
- nucleic acid binding
- RNA methyltransferase activity
- site-specific DNA-methyltransferase (adenine-specific) activity
- U2 snRNA 2'-O-methyladenosine m6 methyltransferase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads METTL4 as an antibody target. Whether an autoantibody or antibody against METTL4 could matter depends on whether native METTL4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
METTL4 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 METTL4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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