MRPS7
protein-codingmitochondrial ribosomal protein S7, the group of 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. In the prokaryotic ribosome, the comparable protein is thought to play an essential role in organizing the 3' domain of the 16 S rRNA in the vicinity of the P- and A-sites. Pseudogenes corresponding to this gene are found on chromosomes 8p and 12p. [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 ~4.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *MRPS7* and autosomal recessive primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of June 17, 2024. The *MRPS7* gene encodes the mitochondrial ribosomal subunit S7, a component of the small subunit of the mitochondrial ribosome. The *MRPS7* gene was first reported in relation to autosomal recessive primary mitochondrial disease in 2015 (PMID: 25556185). *MRPS7* has been associated with a single disease entity to date; combined oxidative phosphorylation deficiency 34 [OMIM# 617872]. 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 three unique variants (two missense, one nonsense) identified in two unrelated cases from two publications (PMIDs: 25556185, 36421788). The first reported case was a child with sensorineural hearing loss, failure to thrive, pancytopenia, liver failure and elevated lactate, as well as mitochondrial respiratory chain deficiency with rescue studies performed in fibroblasts (PMID: 25556185). There was a less severely affected sibling with elevated lactate, episodic hypoglycemia, mild learning difficulties, primary adrenal failure, elevated thyroid stimulating hormone, and primary hypogonadism. The second case was a 25-year-old female with bilateral sensorineural hearing loss and premature ovarian insufficiency (PMID: 36421788). The mechanism of disease is 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 June 17, 2024 (SOP Version 10).
Inheritance Pattern: AR
Disease ID:MONDO:0054741
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0054741
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0018706
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Biochemical; Endocrine; Neurologic; Renal
Intervention: Audiologic/Otolaryngologic; Endocrine
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with endocrine abnormalities including adrenal failure, and awareness may allow early medical management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MRPS7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015971.4. 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 | 21 | 22 | |||
| missense | 2 | 59 | 7 | 68 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 3 | 65 | 28 | 0 | 96 |
Highest pathogenic variant AF is 0.0010321337
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057055.2 | 5 | MANE Select | |
| Ensembl | ENSP00000245539.6 | 5 | MANE Select | |
| Ensembl | ENSP00000463683.1 | 4 | Standard | |
| Ensembl | ENSP00000463683.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome - Homo sapiens (human)
- Mitochondrial translation initiation
- Translation
- Metabolism of proteins
- Mitochondrial translation elongation
Biological Process
- ribosomal small subunit assembly
- translation
- mitochondrial translation
- mitochondrial translational elongation
- mitochondrial translational termination
Molecular Function
- RNA binding
- mRNA binding
- structural constituent of ribosome
- rRNA binding
Cellular Component
- mitochondrial inner membrane
- mitochondrial small ribosomal subunit
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000245539
- Coding exons
- 5
- Length
- 4700
- Individuals with no LoFs
- 125734
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125748
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0787 | 150 | 147 | 1.02 | 0.00000863 | 1570 |
| Missense (PolyPhen) | 34 | 40.975 | 0.82977 | 522 | ||
| Synonymous | -1.78 | 69 | 52.6 | 1.31 | 0.00000273 | 472 |
| Loss of Function | 1.30 | 6 | 10.5 | 0.569 | 4.53e-7 | 135 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000072 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Combined oxidative phosphorylation deficiency 34 (COXPD34) [MIM:617872]: An autosomal recessive disorder caused by mitochondrial dysfunction and combined respiratory chain deficiencies of complexes I, III and IV. Clinical manifestations are variable and include congenital sensorineural deafness, lactic acidemia, and progressive hepatic and renal failure. {ECO:0000269|PubMed:25556185}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.240
Intolerance Scores
- LoFtool
- 0.613
- RVIS EVS
- 0.73
- RVIS percentile EVS
- 86.08
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.919
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |