TONSL

tonsoku like, DNA repair protein, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 8:144428774-144444440

Previous symbols: [ "NFKBIL2" ]

Links

ENSG00000160949 ∙ NCBI:4796 ∙ OMIM:604546 ∙ HGNC:7801 ∙ Uniprot:Q96HA7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia, sponastrime type (Supportive), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, sponastrime type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasia, sponastrime type	AR	General	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	Allergy/Immunology/Infectious; Craniofacial; Dental; Endocrine; Hematologic; Musculoskeletal; Ophthalmologic	30773278; 30773278

ClinVar

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

• not provided (839 variants)
• Inborn genetic diseases (73 variants)
• Sponastrime dysplasia (38 variants)
• TONSL-related condition (11 variants)
• Skeletal dysplaisia with extra-skeletal manifestations (5 variants)
• Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TONSL 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			1	193	27	221
missense		1	393	24	10	428
nonsense	8	3	1			12
start loss						0
frameshift	14	4	3			21
inframe indel			11			11
splice donor/acceptor (+/-2bp)		10	2			12
splice region			25	22	1	48
non coding			7	110	20	137
Total	22	18	418	327	57

Highest pathogenic variant AF is 0.0000197

Variants in TONSL

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

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

Position	Type	Phenotype	Significance	ClinVar
8-144429144-C-T			Likely benign (Apr 09, 2023)
8-144429149-G-A			Likely benign (Jan 25, 2024)
8-144429153-C-G			Uncertain significance (Jan 04, 2022)
8-144429153-C-T			Uncertain significance (Mar 19, 2022)
8-144429155-AAAG-A			Uncertain significance (Dec 13, 2021)
8-144429161-G-C			Likely benign (Aug 04, 2023)
8-144429191-G-A			Likely benign (Jan 01, 2023)
8-144429194-G-A			Likely benign (Nov 27, 2023)
8-144429198-C-A			Uncertain significance (May 12, 2022)
8-144429198-C-T			Uncertain significance (Mar 13, 2022)
8-144429199-C-A			Uncertain significance (Sep 21, 2021)
8-144429200-C-T			Likely benign (Jan 12, 2024)
8-144429203-C-T			Likely benign (May 20, 2023)
8-144429207-C-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
8-144429228-G-C		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
8-144429230-G-T			Uncertain significance (Jun 20, 2022)
8-144429233-C-A		Sponastrime dysplasia	Uncertain significance (Oct 25, 2022)
8-144429239-C-T			Likely benign (Sep 12, 2023)
8-144429252-C-T			Uncertain significance (Jun 05, 2022)
8-144429253-G-A			Uncertain significance (May 24, 2022)
8-144429259-T-C			Uncertain significance (Jun 15, 2022)
8-144429276-C-T			Uncertain significance (Feb 04, 2022)
8-144429278-G-A			Likely benign (Sep 09, 2023)
8-144429284-C-A			Likely benign (Dec 25, 2023)
8-144429287-G-A			Likely benign (May 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TONSL	protein_coding	protein_coding	ENST00000409379	26	15663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.60e-13	1.00	125631	0	112	125743	0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0929	822	815	1.01	0.0000527	8761
Missense in Polyphen		235	275.31	0.8536		3116
Synonymous	0.449	344	355	0.970	0.0000228	2930
Loss of Function	3.54	31	60.8	0.510	0.00000307	673

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000624	0.000621
Ashkenazi Jewish	0.00	0.00
East Asian	0.000767	0.000761
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000583	0.000572
Middle Eastern	0.000767	0.000761
South Asian	0.000393	0.000392
Other	0.000332	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the MMS22L-TONSL complex, a complex that stimulates the recombination-dependent repair of stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication by promoting homologous recombination-mediated repair of replication fork- associated double-strand breaks. It may act by mediating the assembly of RAD51 filaments on ssDNA. Within the complex, may act as a scaffold. {ECO:0000269|PubMed:21055983, ECO:0000269|PubMed:21055984, ECO:0000269|PubMed:21055985, ECO:0000269|PubMed:7738005}.

Recessive Scores

• pRec: 0.257

Intolerance Scores

• rvis_EVS: -0.41
• rvis_percentile_EVS: 25.87

Haploinsufficiency Scores

• pHI: 0.117
• hipred: Y
• hipred_score: 0.715
• ghis: 0.631

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Tonsl

Gene ontology

• Biological process: double-strand break repair via homologous recombination;replication fork processing;cytoplasmic sequestering of transcription factor;negative regulation of nucleic acid-templated transcription
• Cellular component: nucleoplasm;DNA replication factor A complex;cytoplasm;nuclear body;FACT complex;MCM complex;nuclear replication fork
• Molecular function: transcription corepressor activity;protein binding;histone binding