SPO11

SPO11 initiator of meiotic double stranded breaks

Basic information

Region (hg38): 20:57329802-57343994

Links

ENSG00000054796 ∙ NCBI:23626 ∙ OMIM:605114 ∙ HGNC:11250 ∙ Uniprot:Q9Y5K1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPO11 gene.

• Inborn genetic diseases (11 variants)
• not provided (1 variants)
• Non-obstructive azoospermia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPO11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			11		1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region		1				1
non coding						0
Total	0	0	11	0	1

Highest pathogenic variant AF is 0.0000265

Variants in SPO11

This is a list of pathogenic ClinVar variants found in the SPO11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-57329907-G-C		not specified	Uncertain significance (Jul 19, 2023)
20-57329968-C-A		not specified	Uncertain significance (Jan 26, 2022)
20-57329973-A-G			Benign (Jun 10, 2018)
20-57329974-C-T		not specified	Uncertain significance (Aug 21, 2023)
20-57331866-C-G		not specified	Uncertain significance (Jan 16, 2024)
20-57331891-A-G		not specified	Uncertain significance (Nov 13, 2023)
20-57333992-T-C		not specified	Uncertain significance (Jan 05, 2022)
20-57333995-A-G		not specified	Uncertain significance (Jun 07, 2023)
20-57334006-A-G		not specified	Uncertain significance (Oct 03, 2022)
20-57334033-G-A		not specified	Uncertain significance (Sep 16, 2021)
20-57334831-G-A		not specified	Uncertain significance (Feb 15, 2023)
20-57335807-C-T		not specified	Uncertain significance (Sep 16, 2021)
20-57335907-G-A		Non-obstructive azoospermia	Likely pathogenic (Aug 23, 2021)
20-57338301-C-A		not specified	Uncertain significance (Aug 12, 2021)
20-57342817-T-C		not specified	Uncertain significance (Jan 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPO11	protein_coding	protein_coding	ENST00000371263	13	14236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.45e-8	0.605	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.975	165	204	0.808	0.00000991	2595
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000395	0.000390
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.000109
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000404	0.000396
Middle Eastern	0.000116	0.000109
South Asian	0.0000364	0.0000327
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Reproduction;Meiotic recombination;Meiosis;Cell Cycle (Consensus)

Recessive Scores

• pRec: 0.164

Intolerance Scores

• loftool: 0.908
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.46

Haploinsufficiency Scores

• pHI: 0.283
• hipred: Y
• hipred_score: 0.585

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0848

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Spo11
• Phenotype: hearing/vestibular/ear phenotype; immune system phenotype; endocrine/exocrine gland phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: meiotic DNA double-strand break processing;DNA catabolic process, endonucleolytic;ovarian follicle development;synaptonemal complex assembly;reciprocal meiotic recombination;male meiosis I;spermatogenesis;spermatid development;female gamete generation;protein localization to chromosome;meiotic DNA double-strand break formation;meiotic telomere clustering;oogenesis;double-strand break repair involved in meiotic recombination
• Cellular component: chromosome, telomeric region
• Molecular function: DNA binding;DNA topoisomerase type II (ATP-hydrolyzing) activity;protein binding;ATP binding;endodeoxyribonuclease activity, producing 3'-phosphomonoesters;metal ion binding