RMND1
protein-codingrequired for meiotic nuclear division 1 homolog
Gene summary
The protein encoded by this gene belongs to the evolutionary conserved sif2 family of proteins that share the DUF155 domain in common. This protein is thought to be localized in the mitochondria and involved in mitochondrial translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-11. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]
- C6orf96
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013969
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013969
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013969
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013969
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *RMND1* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of September 7, 2022.The *RMND1* gene encodes required for meiotic nuclear division 1 homolog, which functions in mitochondrial translation. The *RMND1* gene was first reported in relation to primary mitochondrial disease in 2012 (PMID 23022099). While various names have been given to the constellation of features seen in those with *RMND1*-related disease, including autosomal recessive combined oxidative phosphorylation deficiency 11 (MIM 614922), pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the *RMND1* phenotype has been lumped into one disease entity according to the ClinGen Lumping and Splitting Framework. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included eight unique variants (two missense, two frameshift, two consensus splice-site, one stop-gained and one extension variant) from six cases across four publications (PMIDs: 23022099, 25058219, 26395190, 27412952). The mechanism of disease appears to be loss of function. This gene-disease relationship is also supported by a biochemical function to anchor or stabilize the mitochondrial ribosome near the sites of mRNA maturation, shRNA knockdown of RMND1 in HeLa cells showed significantly decreased complex I, III and IV activities and diminished mitochondrial protein synthesis (PMIDs: 23022099, 25604853). In summary, there is definitive evidence to support the relationship between *RMND1* and primary mitochondrial disease. This relationship has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on September 7, 2022 (SOP Version 9).
Inheritance Pattern: AR
Disease ID:MONDO:0013969
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal
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 RMND1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017909.4. 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 | 5 | 47 | 1 | 53 | ||
| missense | 5 | 7 | 122 | 12 | 2 | 148 |
| nonsense | 2 | 4 | 1 | 7 | ||
| start loss | 0 | |||||
| frameshift | 13 | 14 | 27 | |||
| splice donor/acceptor (+/-2bp) | 2 | 10 | 3 | 15 | ||
| Total | 22 | 35 | 131 | 59 | 3 | 250 |
Highest pathogenic variant AF is 0.00035761317
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060379.2 | 11 | MANE Select | |
| Ensembl | ENSP00000412708.2 | 11 | MANE Select | |
| RefSeq | NP_001258866.1 | 10 | Standard | |
| Ensembl | ENSP00000336683.4 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- translation
- positive regulation of mitochondrial translation
Molecular Function
- protein binding
Cellular Component
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367303
- Coding exons
- 11
- Length
- 47271
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 55
- Defined
- 125741
- p
- 0.000219
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.765 | 201 | 234 | 0.859 | 0.0000116 | 2967 |
| Missense (PolyPhen) | 54 | 81.812 | 0.66005 | 1073 | ||
| Synonymous | -0.0400 | 84 | 83.5 | 1.01 | 0.00000441 | 838 |
| Loss of Function | 1.17 | 17 | 23.0 | 0.738 | 0.00000115 | 292 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome (PubMed:23022098, PubMed:25604853). {ECO:0000269|PubMed:23022098, ECO:0000269|PubMed:25604853}.;
- Disease
- DISEASE: Combined oxidative phosphorylation deficiency 11 (COXPD11) [MIM:614922]: A severe, multisystemic, autosomal recessive, disorder characterized by deficiencies of multiple mitochondrial respiratory enzymes leading to neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures. {ECO:0000269|PubMed:23022098, ECO:0000269|PubMed:23022099, ECO:0000269|PubMed:25604853, ECO:0000269|PubMed:26238252}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.873
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.807
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |