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

  • 3q13.33-q21.1
  • GRCh37/hg19 chr3: 121,902,530-122,005,344
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr3: 122,183,668-122,291,629
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000003.11) (NC_000003.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Heterozygous loss of function CASR mutations are associated with familial hypocalciuric hypercalcemia (MIM# 145980) which is essentially a benign condition requiring no medical management. Homozygous loss of function mutations and some heterozygous dominant negative mutations cause neonatal severe hyperparathyroidism (NSHPT) (MIM #239200). Some gain of function mutations and other missense mutations have been reported with familial isolated hypoparathyroidism (MIM #146200), and idiopathic generalized epilepsy-8 (MIM #612899). There are no reports of heterozygous deletions or loss of function mutations leading to a clinically significant phenotype. For review please see Hendy et al., PMID: 11013439 and also the CASR Mutation Database: Furthermore, CNVs encompassing CASR have been reported in control populations: PMID 21841781:From Cooper et al., the incidence of observed losses of CASR was 1/15,767 cases vs 4/8,329 controls. From DGV, PMID 19592680 reports a 2.7 kb deletion that overlaps with the terminal exon of CASR in 22/2026 healthy individuals.

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