POP1
protein-codingPOP1 homolog, ribonuclease P/MRP subunit
Gene summary
This gene encodes the protein subunit of two different small nucleolar ribonucleoprotein complexes: the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. The encoded protein is a ribonuclease that localizes to the nucleus and functions in pre-RNA processing. This protein is also an autoantigen in patients suffering from connective tissue diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0054561
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011773
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0054561
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0054561
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
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 POP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001145860.2. 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 | 2 | 117 | 7 | 126 | ||
| missense | 3 | 3 | 213 | 21 | 4 | 244 |
| nonsense | 9 | 6 | 15 | |||
| start loss | 0 | |||||
| frameshift | 9 | 2 | 6 | 17 | ||
| splice donor/acceptor (+/-2bp) | 5 | 2 | 7 | |||
| Total | 21 | 16 | 223 | 138 | 11 | 409 |
Highest pathogenic variant AF is 0.0002869044
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001139332.1 | 15 | MANE Select | |
| Ensembl | ENSP00000385787.2 | 15 | MANE Select | |
| RefSeq | NP_001139333.1 | 15 | Standard | |
| RefSeq | NP_055844.2 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
- tRNA processing
- Metabolism of RNA
- tRNA processing in the nucleus
Biological Process
- tRNA 5'-leader removal
- tRNA processing
- tRNA catabolic process
- RNA phosphodiester bond hydrolysis, endonucleolytic
Molecular Function
- ribonuclease MRP activity
- RNA binding
- ribonuclease P activity
- protein binding
Cellular Component
- ribonuclease MRP complex
- extracellular space
- nucleoplasm
- nucleolar ribonuclease P complex
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000401707
- Coding exons
- 15
- Length
- 42538
- Individuals with no LoFs
- 125569
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 179
- Defined
- 125748
- p
- 0.000712
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.12 | 495 | 570 | 0.868 | 0.0000332 | 6670 |
| Missense (PolyPhen) | 144 | 201.29 | 0.71539 | 2350 | ||
| Synonymous | 1.28 | 193 | 217 | 0.889 | 0.0000132 | 2026 |
| Loss of Function | 2.97 | 29 | 52.2 | 0.556 | 0.00000300 | 587 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0012 | 0.0012 | notable |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00089 | 0.00089 | rare |
| South Asian | 0.0012 | 0.0011 | notable |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of RNase MRP.;
- Disease
- DISEASE: Anauxetic dysplasia 2 (ANXD2) [MIM:617396]: An autosomal recessive spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability. {ECO:0000269|PubMed:21455487, ECO:0000269|PubMed:27380734, ECO:0000269|PubMed:28067412}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0892
Intolerance Scores
- LoFtool
- 0.969
- RVIS EVS
- -1.23
- RVIS percentile EVS
- 5.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.850
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |