MRPL40
protein-codingmitochondrial ribosomal protein L40, the group of Large subunit mitochondrial ribosomal proteins|Mitochondrial ribosomal proteins
Gene summary
Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Deletions in this gene may contribute to the etiology of velo-cardio-facial syndrome and DiGeorge syndrome. [provided by RefSeq, Jul 2008]
- NLVCF
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.5 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 MRPL40 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003776.4. 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 | 6 | 2 | 8 | |||
| missense | 41 | 2 | 43 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 45 | 8 | 2 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003767.2 | 4 | MANE Select | |
| Ensembl | ENSP00000333401.3 | 4 | MANE Select | |
| RefSeq | NP_001305080.1 | 3 | Standard | |
| Ensembl | ENSP00000596403.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mitochondrial translation initiation
- Translation
- Metabolism of proteins
- Mitochondrial translation elongation
- Mitochondrial translation termination
Biological Process
- anatomical structure morphogenesis
- mitochondrial translational elongation
- mitochondrial translational termination
Molecular Function
- RNA binding
- protein binding
Cellular Component
- nucleus
- mitochondrion
- mitochondrial inner membrane
- mitochondrial ribosome
- mitochondrial large ribosomal subunit
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000333130
- Coding exons
- 4
- Length
- 4174
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 49
- Defined
- 125748
- p
- 0.000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.525 | 122 | 107 | 1.14 | 0.00000558 | 1318 |
| Missense (PolyPhen) | 39 | 32.356 | 1.2053 | 412 | ||
| Synonymous | -0.799 | 48 | 41.5 | 1.16 | 0.00000206 | 396 |
| Loss of Function | 2.05 | 4 | 11.5 | 0.347 | 6.84e-7 | 122 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.000098 | 0.000079 | rare |
| South Asian | 0.00074 | 0.00065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0615
Intolerance Scores
- LoFtool
- 0.738
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 60.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |