RMRP
ncRNARNA component of mitochondrial RNA processing endoribonuclease
Gene summary
This gene encodes the RNA component of mitochondrial RNA processing endoribonuclease, which cleaves mitochondrial RNA at a priming site of mitochondrial DNA replication. This RNA also interacts with the telomerase reverse transcriptase catalytic subunit to form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase activity and produces double-stranded RNAs that can be processed into small interfering RNA. Mutations in this gene are associated with cartilage-hair hypoplasia.[provided by RefSeq, Mar 2010]
- CHH
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
GenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009595
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009595
Submitter: ClinGen
RMRP was first reported in relation to autosomal recessive cartilage-hair hypoplasia in 2001 (Ridanpaa et al, PMID: 11207361). The phenotype of CHH patients can be variable but may include: shortened limbs, short stature, metaphysical dysplasia, fine, sparse and/or light-colored hair, hematologic abnormalities and a spectrum of combined immunodeficiency. RMRP encodes an untranslated RNA component of mitochondrial RNA processing endoribonuclease that is critical for DNA replication; defective RMRP functioning ultimately impairs cell proliferation and differentiation. Over 130 variants (insertions, duplications and missense variations) have been reported in numerous publications (PMIDs: 11207361, 14569125, 16254002, 17015150, 18978468, 19150606, 21063072, 21570718, 25663137, 28094436, 28126377) and many are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is reported to be loss of function. Heterozygous carriers have not been shown to have a clinical phenotype. This gene-disease association is also supported by experimental evidence, PMIDs 20133615, 24889605, 10911993, 18804272). In summary, RMRP is definitively associated with autosomal recessive cartilage-hair hypoplasia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
Inheritance Pattern: AR
Disease ID:MONDO:0009595
Submitter: Natera
Inheritance Pattern: AR
Disease ID:MONDO:0009595
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009595
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009595
Submitter: Myriad Women's Health
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic
Intervention: Allergy/Immunology/Infectious; Hematologic; Oncologic
Rationale: There is a wide range of manifestations and severity, and while the disorder may be frequently (though not always) easily clinically recognizable, there is an increased risk reported of hematologic, immunologic, and oncologic complications, and surveillance and prompt treatment may be beneficial; HSCT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RMRP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 0 | |||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 5 | 8 | ||
| Total | 1 | 2 | 5 | 0 | 0 | 8 |
Highest pathogenic variant AF is 0.000151436
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| No transcripts match your selected source or search query. | ||||
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein- coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair. {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:8810265}.;
Recessive Scores
- pRec
- 0.461
Intolerance Scores
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.914