MRPS23
protein-codingmitochondrial ribosomal protein S23, the group of Small 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 28S subunit protein. A pseudogene corresponding to this gene is found on chromosome 7p. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0033534
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0033533
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *MRPS23* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of November 4, 2024. The *MRPS23* gene encodes the mitochondrial ribosomal protein S23. The *MRPS23* gene was first reported in relation to autosomal recessive primary mitochondrial disease in 2016 (PMID: 26741492). *MRPS23* has been associated with a single disease entity to date; combined oxidative phosphorylation deficiency 46 [OMIM# 618952]. This is one disease entity according to the ClinGen Lumping and Splitting Framework, and is considered a primary mitochondrial disease. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included two homozygous missense variants identified in six unrelated cases from two publications (PMIDs: 26741492, 38086984). The NM_016070:c.119C>T (p.Pro40Leu) variant was seen in affected individuals from five families from the Hmong hill tribe in Thailand (PMID: 38086984). Clinical features in affected individuals included hypoglycemia, liver disease, altered consciousness, vomiting, delayed growth, developmental delay, hearing loss, and lactic acidosis. The mechanism of disease is suspected to be loss of function. This gene-disease relationship is also supported by a biochemical function shared with other genes associated with primary mitochondrial disease (PMID: 33340416). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on November 4, 2024 (SOP Version 11).
Inheritance Pattern: Unknown
Disease ID:MONDO:0033534
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Gastrointestinal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MRPS23 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016070.4. 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 | 1 | 22 | 2 | 25 | ||
| missense | 1 | 1 | 34 | 4 | 1 | 41 |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 1 | 1 | 42 | 26 | 3 | 73 |
Highest pathogenic variant AF is 0.0000020521547
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057154.2 | 5 | MANE Select | |
| Ensembl | ENSP00000320184.8 | 5 | MANE Select | |
| Ensembl | ENSP00000463677.1 | 4 | Standard | |
| Ensembl | ENSP00000463677.1 | 4 | 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
- mitochondrial translational elongation
- mitochondrial translational termination
Molecular Function
- RNA binding
- structural constituent of ribosome
- protein binding
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- ribosome
- nuclear membrane
- intermediate filament cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000313608
- Coding exons
- 5
- Length
- 10576
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.169 | 107 | 112 | 0.955 | 0.00000638 | 1217 |
| Missense (PolyPhen) | 38 | 33.459 | 1.1357 | 371 | ||
| Synonymous | 0.166 | 43 | 44.4 | 0.968 | 0.00000268 | 373 |
| Loss of Function | 1.99 | 3 | 9.71 | 0.309 | 5.71e-7 | 99 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Note=Defects in MRPS23 may play a role in mitochondrial disorders characterized by combined respiratory chain complex deficiencies. {ECO:0000269|PubMed:26741492}.;
Recessive Scores
- pRec
- 0.0793
Intolerance Scores
- LoFtool
- 0.299
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |