ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000004.11) (NC_000004.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

There is suggestion that polymorphisms within DRD5 may be associated with susceptibility to both ADHD and blepharospasm (see OMIM entry for additional detail). Available data does not demonstrate that loss of function mutations of DRD5 result in these phenotypes. There is a report (PMID: 7633397) of a nonsense mutation identified in two unrelated patients with schizophrenia. However, this mutation was observed at a similar frequency amongst ethnicity matched controls, and did not segregate with disease within the one family available for study. However, a post-hoc analysis of combined measures of frontal lobe function hinted that heterozygotes for C335X may have a vulnerability to mild impairment, but, per the authors, these findings must be interpreted with caution.

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

Triplosensitivity phenotype comment:

Though no evidence was found linking DRD5 duplications alone with a specific phenotype, there has been a report of a 482 kb gain encompassing DRD5 (and 2 other genes) in a proband with ADHD inherited from an affected father (PMID:21832240)