ESPL1
protein-codingextra spindle pole bodies like 1, separase
Gene summary
Stable cohesion between sister chromatids before anaphase and their timely separation during anaphase are critical for chromosome inheritance. In vertebrates, sister chromatid cohesion is released in 2 steps via distinct mechanisms. The first step involves phosphorylation of STAG1 (MIM 604358) or STAG2 (MIM 300826) in the cohesin complex. The second step involves cleavage of the cohesin subunit SCC1 (RAD21; MIM 606462) by ESPL1, or separase, which initiates the final separation of sister chromatids (Sun et al., 2009 [PubMed 19345191]).[supplied by OMIM, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.3 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 ESPL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012291.5. 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 | 3 | 11 | 1 | 15 | ||
| missense | 197 | 21 | 8 | 226 | ||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 208 | 32 | 9 | 249 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036423.4 | 30 | MANE Select | |
| Ensembl | ENSP00000257934.4 | 30 | MANE Select | |
| Ensembl | ENSP00000447054.1 | 1 | Standard | |
| Ensembl | ENSP00000456450.2 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| espl1 | Danio rerio | Structure: post-vent region Quality: curvature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Oocyte meiosis - Homo sapiens (human)
- Cell Cycle
- Regulation of sister chromatid separation at the metaphase-anaphase transition
- DroToll-like
Biological Process
- mitotic sister chromatid segregation
- meiotic spindle organization
- mitotic cytokinesis
- proteolysis
- apoptotic process
Molecular Function
- catalytic activity
- cysteine-type endopeptidase activity
- protein binding
- cysteine-type peptidase activity
Cellular Component
- nucleus
- cytoplasm
- centrosome
- cytosol
- mitotic spindle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000257934
- Coding exons
- 30
- Length
- 25345
- Individuals with no LoFs
- 125570
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 177
- Defined
- 125747
- p
- 0.000704
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.31 | 755 | 1.17e+3 | 0.645 | 0.0000675 | 13530 |
| Missense (PolyPhen) | 116 | 314.68 | 0.36863 | 3910 | ||
| Synonymous | 1.51 | 447 | 489 | 0.913 | 0.0000262 | 4579 |
| Loss of Function | 8.38 | 9 | 99.0 | 0.0909 | 0.00000550 | 1061 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0046 | 0.0046 | notable |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00090 | 0.00089 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00077 | 0.00076 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.291
- RVIS EVS
- 1.8
- RVIS percentile EVS
- 96.89
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.494
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |