TONSL

Chr 8AR

tonsoku like, DNA repair protein

Also known as: IKBR, NFKBIL2, SEMDSP

NCBI Gene: 4796ENSG00000160949UniProt: Q96HA7

The protein functions as a component of the MMS22L-TONSL complex that promotes homologous recombination-mediated repair of DNA double-strand breaks during replication and acts as a histone reader that recognizes newly synthesized histones. Mutations cause spondyloepimetaphyseal dysplasia, sponastrime type, a skeletal dysplasia affecting spine and bone development. This condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Spondyloepimetaphyseal dysplasia, sponastrime typeMIM #271510
AR
0
Active trials
13
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
0.69
LOEUF
LOF
Mechanism· G2P
Clinical Summary— TONSL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 155 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.54
OE 0.51 (0.38–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.09Z-score
OE missense 1.01 (0.95–1.07)
822 obs / 814.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.38–0.69)
0≤0.351.4
Missense OE1.01 (0.95–1.07)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 31 / 60.8Missense obs/exp: 822 / 814.5Syn Z: 0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTONSL-related sponastrime dysplasiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.6443th %ile
LOF
0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic10
VUS155
Likely Benign271
Benign15
Conflicting9
15
Pathogenic
10
Likely Pathogenic
155
VUS
271
Likely Benign
15
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
7
0
15
Likely Pathogenic
9
0
1
0
10
VUS
0
144
10
1
155
Likely Benign
0
11
94
166
271
Benign
0
0
8
7
15
Conflicting
—9
Total17155120174475

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TONSL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients