TONSL

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

Basic information

Region (hg38): 8:144428775-144444440

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 (Definitive), 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 (1080 variants)
Inborn_genetic_diseases (240 variants)
Sponastrime_dysplasia (47 variants)
TONSL-related_disorder (47 variants)
Skeletal_dysplaisia_with_extra-skeletal_manifestations (6 variants)
not_specified (1 variants)
Susceptibility_to_severe_COVID-19 (1 variants)
Spondylometaphyseal_dysplasia (1 variants)
See_cases (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. These statistics are base on transcript: NM_000013432.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	313 clinvar	22 clinvar	339
missense	1 clinvar	6 clinvar	500 clinvar	46 clinvar	6 clinvar	559
nonsense	13 clinvar	7 clinvar	1 clinvar			21
start loss			1			1
frameshift	26 clinvar	13 clinvar	2 clinvar			41
splice donor/acceptor (+/-2bp)	2 clinvar	18 clinvar	2 clinvar			22
Total	42	44	510	359	28

Highest pathogenic variant AF is 0.000058935853

Loading clinvar variants...

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

loftool
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
Phenotype

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