ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000006.11) (NC_000006.12)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
  • Haploinsufficiency Phenotype: OBESITY
Evidence for haploinsufficiency phenotype
PubMed ID Description
10587584 Holder et al (2000) report a girl with early-onset obesity and a balanced translocation between 1p22.1 and 6q16.2. They PCR amplified and sequenced both junctions and found that the translocation deleted only a single base pair of chromosome 6 and none of chromosome 1. On chromosome 6, the translocation breakpoint falls within the first intron of SIM1 and separates the 5' flanking sequence and the first exon from downstream exons. No transcripts on chromosome 1 appear to be disrupted.

Haploinsufficiency phenotype comments:

SIM1 has been associated with a "Prader-Willi-like" phenotype. However, other than Holder et al (described above), all reports in the literature are of deletions that include SIM1 as well as other genes. Furthermore, patients with SIM1 deletions do not always show the PW-like phenotype. For example: PMID 22218741: Rosenfeld et al (2012) used microarray-based comparative genomic hybridization to better correlate 6q deletion regions with specific phenotypes. They report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33. Four individuals have a Prader-Willi-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype.

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