METTL21A
protein-codingmethyltransferase 21A, HSPA lysine, the group of 7BS protein lysine methyltransferases
Gene summary
Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in negative regulation of protein folding and protein methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]
- FAM119A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to METTL21A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001127395.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 27 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 28 | 0 | 0 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001120867.1 | 3 | MANE Select | |
| Ensembl | ENSP00000415115.1 | 3 | MANE Select | |
| RefSeq | NP_001294950.1 | 3 | Standard | |
| RefSeq | NP_001317059.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Protein methylation
Biological Process
- protein methylation
- peptidyl-lysine methylation
- regulation of ATPase activity
Molecular Function
- protein binding
- protein methyltransferase activity
- protein-lysine N-methyltransferase activity
- Hsp70 protein binding
- heat shock protein binding
Cellular Component
- nucleoplasm
- cytoplasm
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000411432
- Coding exons
- 3
- Length
- 45298
- Individuals with no LoFs
- 125510
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 238
- Defined
- 125748
- p
- 0.000947
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0422 | 123 | 122 | 1.01 | 0.00000641 | 1402 |
| Missense (PolyPhen) | 44 | 42.569 | 1.0336 | 515 | ||
| Synonymous | 0.806 | 42 | 49.2 | 0.854 | 0.00000275 | 442 |
| Loss of Function | 0.834 | 6 | 8.65 | 0.694 | 5.18e-7 | 91 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0043 | 0.0043 | notable |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0030 | 0.0030 | notable |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00076 | 0.00076 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00083 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein-lysine methyltransferase that selectively trimethylates residues in heat shock protein 70 (HSP70) family members. Contributes to the in vivo trimethylation of Lys residues in HSPA1 and HSPA8. In vitro methylates 'Lys-561' in HSPA1, 'Lys- 564' in HSPA2, 'Lys-585' in HSPA5, 'Lys-563' in HSPA6 and 'Lys- 561' in HSPA8. {ECO:0000269|PubMed:22948820, ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:23921388}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |