ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000021.8) (NC_000021.9)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22495309 O'Roak et al. (2012) performed WES on 189 trios from the Simons Simpex Collection. They found a de novo splice site mutation in DYRK1A in a female with autism and microcephaly.
21294719 van Bon et al. (2011) analyzed 3009 patients with ID for CNVs in DYRK1A using Affy 250K SNP array data. Patients with pathogenic CNVs greater than 150 kb were excluded from the study. One deletion was identified and confirmed by qPCR and a NimbleGen custom array. The deletion was 52 kb, removing the last 3 exons of DYRK1A (no other genes are involved), and de novo. The proband had ID, microcephaly, and "anxious autistic behavior".
18405873 Moller et al. (2008) identified two unrelated patients with similar phenotypes with de novo balanced translocations that disrupted DYRK1A. The first patient was 24 months at time of the report and had microcephaly, DD, feeding problems, febrile convulsions, and "hand stereotypes". For this patient, a de novo balanced tranlocation t(9;21)(p12;q22) was identified with the chr9 breakpoint in a seg dup region with no genes. The chr21 breakpoint occurred within the second intron of DYRK1A as determined by FISH and tiling path BAC array. The second patient had severe ID, microcephaly, feeding problems, and febrile convulsions. She had a de novo balanced translocation t(2;21)(q22;q22) with the chr2 breakpoint in LRP1B and the chr21 breakpoint in DYRK1A.

Haploinsufficiency phenotype comments:

Mutations in this gene are associated with autosomal dominant mental retardation-7 (MRD7): ID and microcephaly.

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

Triplosensitivity phenotype comment:

This gene is located in the Down Syndrome Critical Region. Note: PMID 17145134: Dowjat et al. (2007) analyzed DYRK1A protein in 17 DS brain tissues vs 12 control brain tissues. They report a ~1.5 fold increase in protein in the DS samples as compared to the controls.