SPO11
protein-codingSPO11 initiator of meiotic double stranded breaks
Gene summary
Meiotic recombination and chromosome segregation require the formation of double-strand breaks (DSBs) in paired chromosome homologs. During meiosis in yeast, a meiotic recombination protein is covalently-linked to the 5' end of DSBs and is essential for the formation of DSBs. The protein encoded by this gene is similar in sequence and conserved features to the yeast meiotic recombination protein. The encoded protein belongs to the TOP6A protein family. Several transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.2 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 SPO11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012444.3. 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 | 1 | 1 | ||||
| missense | 39 | 1 | 1 | 41 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 39 | 1 | 1 | 42 |
Highest pathogenic variant AF is 0.0000063700923
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036576.1 | 13 | MANE Select | |
| Ensembl | ENSP00000360310.3 | 13 | MANE Select | |
| RefSeq | NP_937998.1 | 12 | Standard | |
| Ensembl | ENSP00000316034.4 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Reproduction
- Meiotic recombination
- Meiosis
- Cell Cycle
Biological Process
- meiotic DNA double-strand break processing
- DNA catabolic process, endonucleolytic
- ovarian follicle development
- synaptonemal complex assembly
- reciprocal meiotic recombination
Molecular Function
- DNA binding
- DNA topoisomerase type II (ATP-hydrolyzing) activity
- protein binding
- ATP binding
- endodeoxyribonuclease activity, producing 3'-phosphomonoesters
Cellular Component
- chromosome, telomeric region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371263
- Coding exons
- 13
- Length
- 14236
- Individuals with no LoFs
- 125687
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 61
- Defined
- 125748
- p
- 0.000243
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.975 | 165 | 204 | 0.808 | 0.00000991 | 2595 |
| Missense (PolyPhen) | 36 | 51.998 | 0.69233 | 674 | ||
| Synonymous | -0.801 | 79 | 70.5 | 1.12 | 0.00000355 | 728 |
| Loss of Function | 1.17 | 15 | 20.8 | 0.722 | 9.28e-7 | 282 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00040 | 0.00040 | rare |
| South Asian | 0.000036 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of a topoisomerase 6 complex specifically required for meiotic recombination. Together with TOP6BL, mediates DNA cleavage that forms the double-strand breaks (DSB) that initiate meiotic recombination. The complex promotes relaxation of negative and positive supercoiled DNA and DNA decatenation through cleavage and ligation cycles. Essential for the phosphorylation of SMC3, HORMAD1 and HORMAD2. {ECO:0000250|UniProtKB:Q9WTK8}.;
Recessive Scores
- pRec
- 0.164
Intolerance Scores
- LoFtool
- 0.908
- RVIS EVS
- 0.46
- RVIS percentile EVS
- 78.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0848
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |