ClinGen Dosage Sensitivity Curation Page

See New Dosage Map New! The ClinGen Dosage Sensitivity curations and downloads that are available at this site are now also available at Click on the button to access Dosage Sensitivity in the context of ClinGen's other curated information, including Gene-Disease Validity and Clinical Actionability.


  • Curation Status: Complete

Location Information

Select assembly: (NC_000021.8) (NC_000021.9)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

From OMIM #600909: "[Holoprosencephaly type 1 (HPE1)] maps to the same interval as LSS on chromosome 21. LSS was considered an excellent candidate gene for HPE because of the requirement for cholesterol modification of the Sonic hedgehog protein (SHH; 600725), an HPE-associated protein, for correct patterning activity. Despite an extensive pedigree analysis of numerous polymorphisms, as well as complementation studies in yeast on one of the missense mutations, Roessler et al. (1999) could find no evidence that the LSS gene is responsible for HPE1, thus implicating another gene located in the 21q22.3 region in HPE pathogenesis [PMID: 10598817]." Additionally, Rosenfeld et a. (2010) (PMID: 20066439) identified 3 individuals with deletions involving LSS - one deletion of LSS alone, and two other deletions involving both LSS and TMEM1. The individual with the deletion of LSS alone showed no signs of HPE on MRI examination. The others, with the larger deletions involving TMEM1, did show a microform form of HPE.

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