TONSL
protein-codingtonsoku like, DNA repair protein, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus. [provided by RefSeq, Jul 2008]
- NFKBIL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0010068
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0010068
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0010068
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0010068
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Craniofacial; Dental; Endocrine; Hematologic; Musculoskeletal; Ophthalmologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TONSL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013432.5. 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 | 6 | 371 | 13 | 390 | ||
| missense | 1 | 4 | 538 | 55 | 5 | 603 |
| nonsense | 13 | 9 | 1 | 23 | ||
| start loss | 1 | 1 | ||||
| frameshift | 31 | 17 | 2 | 50 | ||
| splice donor/acceptor (+/-2bp) | 1 | 19 | 8 | 28 | ||
| Total | 46 | 49 | 556 | 426 | 18 | 1095 |
Highest pathogenic variant AF is 0.000058935853
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_038460.4 | 26 | MANE Select | |
| Ensembl | ENSP00000386239.3 | 26 | MANE Select | |
| Ensembl | ENSP00000602113.1 | 26 | Standard | |
| Ensembl | ENSP00000602113.1 | 26 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- double-strand break repair via homologous recombination
- replication fork processing
- cytoplasmic sequestering of transcription factor
- negative regulation of nucleic acid-templated transcription
Molecular Function
- transcription corepressor activity
- protein binding
- histone binding
Cellular Component
- nucleoplasm
- DNA replication factor A complex
- cytoplasm
- nuclear body
- FACT complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409379
- Coding exons
- 26
- Length
- 15663
- Individuals with no LoFs
- 125631
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 112
- Defined
- 125743
- p
- 0.000445
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0929 | 822 | 815 | 1.01 | 0.0000527 | 8761 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00031 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00077 | 0.00076 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00058 | 0.00057 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- 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
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |