ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
19959528 Kabashi et al. (2010): TARDBP mutations (A315T, G348C and A382T) were tested in cell lines, primary cultured motor neurons and living zebrafish embryos. Results showed that TARDBP mutations cause motor neuron defects and toxicity, suggesting that both a toxic gain of function as well as a novel loss of function may be involved in the molecular mechanism by which mutant TDP-43 contributes to disease pathogenesis.
18931000 Daoud et al. (2009): A truncating mutation in the last exon of TARDP was detected in a 63 year old male with sporadic ALS. The same mutation was reported in a young male with missense FUS mutation (PMID:26452761). In that case, the patient had early onset and death. The authors concluded that the more aggressive disease phenotype was due to the combination of mutations.

Haploinsufficiency phenotype comments:

TARDPB mutations occur in about 3% of patients with autosomal dominant familial ALS and in 1.5% of patients with sporadic disease. Almost all disease-causing mutations to date have been missense and in-frame indels. The exception is a recurrent, 3' truncating mutation p.Y374*. The combined data suggest that abnormal TARDPB protein rather than haploinsufficiency, is the primary cause of disease.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity