ClinGen Dosage Sensitivity Curation Page


  • 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