TONSL

Chr 8AR

tonsoku like, DNA repair protein

Also known as: IKBR, NFKBIL2, SEMDSP

NCBI Gene: 4796 ENSG00000160949 UniProt: Q96HA7 OMIM: 604546

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spondyloepimetaphyseal dysplasia, sponastrime typeMIM #271510

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

gnomad: Error: Service overloaded