NSUN4
protein-codingNOP2/Sun RNA methyltransferase 4, the group of NOP2/Sun RNA methyltransferase family
Gene summary
Enables mRNA (cytidine-5-)-methyltransferase activity; mitochondrial ribosomal large subunit rRNA binding activity; and rRNA (cytosine-C5-)-methyltransferase activity. Involved in RNA metabolic process and mitochondrial large ribosomal subunit assembly. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.4 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 NSUN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199044.4. 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 | 2 | 2 | ||||
| missense | 51 | 51 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 57 | 0 | 0 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_950245.2 | 6 | MANE Select | |
| Ensembl | ENSP00000419740.1 | 6 | MANE Select | |
| RefSeq | NP_001243056.1 | 5 | Standard | |
| RefSeq | NP_001243057.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- rRNA processing
- rRNA modification in the mitochondrion
- Metabolism of RNA
- rRNA processing in the mitochondrion
Biological Process
- rRNA methylation
- mature ribosome assembly
- positive regulation of mitochondrial translation
Molecular Function
- protein binding
- methyltransferase activity
- rRNA (cytosine-C5-)-methyltransferase activity
- small ribosomal subunit rRNA binding
Cellular Component
- mitochondrial matrix
- mitochondrial large ribosomal subunit
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000474844
- Coding exons
- 6
- Length
- 24976
- Individuals with no LoFs
- 125512
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 235
- Defined
- 125747
- p
- 0.000935
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.832 | 183 | 218 | 0.841 | 0.0000113 | 2463 |
| Missense (PolyPhen) | 72 | 82.677 | 0.87086 | 935 | ||
| Synonymous | 1.03 | 72 | 84.0 | 0.857 | 0.00000415 | 795 |
| Loss of Function | 1.87 | 13 | 22.6 | 0.575 | 0.00000162 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0020 | 0.0020 | notable |
| Latino/Admixed American | 0.00078 | 0.00078 | rare |
| Ashkenazi Jewish | 0.0034 | 0.0034 | notable |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00045 | 0.00045 | rare |
| South Asian | 0.0021 | 0.0021 | notable |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in mitochondrial ribosome assembly. 5- methylcytosine rRNA methyltransferase that probably is involved in mitochondrial ribosome small subunit (SSU) maturation by methylation of mitochondrial 12S rRNA; the function is independent of MTERFD2/MTERF4 and assembled mitochondrial ribosome large subunit (LSU). Targeted to LSU by MTERFD2/MTERF4 and probably is involved in a final step in ribosome biogenesis to ensure that SSU and LSU are assembled. In vitro can methylate 16S rRNA of the LSU; the methylation is enhanced by MTERFD/MTERF4. {ECO:0000269|PubMed:21531335, ECO:0000269|PubMed:23022348}.;
Recessive Scores
- pRec
- 0.0938
Intolerance Scores
- LoFtool
- 0.906
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.49
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.925
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |