TONSL

Chr 8AR

tonsoku like, DNA repair protein

Also known as: IKBR, NFKBIL2, SEMDSP

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.691 OMIM phenotype
Clinical SummaryTONSL
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.54
OE 0.51 (0.380.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.09Z-score
OE missense 1.01 (0.951.07)
822 obs / 814.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.380.69)
00.351.4
Missense OE1.01 (0.951.07)
00.61.4
Synonymous OE0.97
01.21.6
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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗