TONSL

Chr 8q24.3

tonsoku like, DNA repair protein

Aliases:: IKBR
MANE:: ENST00000409379.8

OMIM: 604546 ↗NCBI: 4796 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

TONSL · Q96HA7

v62025-08-01

Predicted Aligned Error matrix for TONSL — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

75.3/ 100

Confident

1,378 residues

Confidence breakdown

Very high(≥ 90)43%
Confident(70–90)30%
Low(50–70)4%
Very low(< 50)24%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

spondyloepimetaphyseal dysplasia, sponastrime type
0.80
SPONASTRIME dysplasia
0.73
hereditary disease
0.47
neurodegenerative disease
0.22
spondylometaphyseal dysplasia
0.12
retinitis pigmentosa
0.11
hepatocellular carcinoma
0.09
Progressive cone dystrophy
0.09
cancer
0.08
Cone rod dystrophy
0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Tonsoku-like protein

Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks (PubMed:21055983, PubMed:21055984, PubMed:21055985, PubMed:21113133, PubMed:26527279, PubMed:27338793, PubMed:27797818, PubMed:29478807, PubMed:30773278). The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication (PubMed:21055983, PubMed:21055984, PubMed:21055985). It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs (PubMed:21055983, PubMed:21055984, PubMed:21055985, PubMed:27797818, PubMed:29478807). Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination (PubMed:27797818, PubMed:29478807). Within the complex, TONSL acts as a histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones (PubMed:27338793, PubMed:29478807). Specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) and histone H3.1 (PubMed:27338793)