ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
  • Haploinsufficiency Phenotype: Schizophrenia
Evidence for haploinsufficiency phenotype
PubMed ID Description
24853937 Takata 2014 reports 2 de novo loss of function mutations among 231 patients with schizophrenia phenotype from exome sequencing data. No loss of function variants found in the 34 controls. The two patients with the mutations also had obsessive compulsive disorder.
26974950 Singh 2016 investigated several different patient cohorts (schizophrenia and patient groups with developmental delays). In the schizophrenia cohorts, they observed a total of 10 loss-of-function mutations at least 4 of which were de novo. Statistical analysis of case versus controls were significant for elevation of SETD1A LOF mutations. In the developmental delay cohorts, 6 additional LOF mutations were detected. Two had unknown inheritance, 2 were de novo and 2 were maternally inherited without clinical information on the mothers. In total 16 SETD1A LOF of function mutations were identified in patients with at least 6 de novo mutations. Only two LOF mutations observed among 58,404 controls (both in ExAC). Based on the phenotypes of the patients, the full clinical spectrum associated with SETD1A LOF mutations is yet to be determined, but includes schizophrenia, likely developmental delay, and possibly facial dysmorphism, epilepsy and personality disorder.

Haploinsufficiency phenotype comments:

While focal deletions of SETD1A have not been described, emerging evidence demonstrates a clear association between SETD1A LOF mutations and schizophrenia and likely additional neurodevelopmental phenotypes.

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