ClinGen Dosage Sensitivity Curation Page

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  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
  • Haploinsufficiency Phenotype: GITELMAN SYNDROME; GTLMNS
Evidence for haploinsufficiency phenotype
PubMed ID Description
21415153 In 51 patients with a clinical diagnosis of Gitelman's syndrome and a demonstrated heterozygous sequence mutation, nine deletions and two duplications (22%) were detected using MLPA targeting the SLC12A3 gene

Haploinsufficiency phenotype comments:

Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman's syndrome (GS), a disorder inherited as an autosomal recessive trait. The prevalence is estimated at approximately 1:40,000 and accordingly, the prevalence of heterozygotes is approximately 1% in Caucasian populations, making it one of the most frequent inherited renal tubular disorders (PMID:18667063). Most mutations are missense mutations substituting conserved amino acid residues within putative functional domains of the NCCT, whereas nonsense, frameshift and splice-site defects, and gene rearrangements are less frequent. It is noteworthy that in up to 40% of patients with a clinical diagnosis of Gitelman's syndrome only a single mutation is detected, instead of being compound heterozygous or homozygous (PMID:17061123).

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

Triplosensitivity phenotype comment:

No literature identified.