PARL
protein-codingpresenilin associated rhomboid like, the group of Rhomboid family
Gene summary
This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]
- PSARL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PARL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018622.7. 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 | 4 | 3 | 7 | |||
| missense | 61 | 61 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 68 | 3 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061092.3 | 10 | MANE Select | |
| Ensembl | ENSP00000325421.5 | 10 | MANE Select | |
| RefSeq | NP_001032728.1 | 9 | Standard | |
| RefSeq | NP_001311365.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| parlb | Danio rerio | Structure: caudal tuberculum Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteolysis
- regulation of mitochondrion organization
- regulation of proteolysis
- membrane protein proteolysis
- regulation of protein targeting to mitochondrion
Molecular Function
- endopeptidase activity
- serine-type endopeptidase activity
- protein binding
Cellular Component
- nucleus
- mitochondrion
- mitochondrial inner membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000317096
- Coding exons
- 10
- Length
- 55549
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125748
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0792 | 210 | 207 | 1.02 | 0.0000103 | 2458 |
| Missense (PolyPhen) | 31 | 38.298 | 0.80944 | 486 | ||
| Synonymous | -1.42 | 91 | 75.3 | 1.21 | 0.00000409 | 727 |
| Loss of Function | 2.48 | 10 | 22.8 | 0.439 | 0.00000104 | 251 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00035 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptoptic signals (By similarity). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain. {ECO:0000250, ECO:0000269|PubMed:14732705, ECO:0000269|PubMed:17116872}.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- LoFtool
- 0.925
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- N
- Indispensability score
- 0.481
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |