ClinGen Dosage Sensitivity Curation Page
SLC12A3
- Curation Status: Complete
- id: ISCA-25631
- Date last evaluated: 2012-02-23
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about SLC12A3 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/6559
- OMIM: https://omim.org/entry/600968
- ClinGen Haploinsufficiency Score: Gene associated with autosomal recessive phenotype
- ClinGen Triplosensitivity Score: 0
- Haploinsufficiency score: Gene associated with autosomal recessive phenotype
- Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
- Haploinsufficiency Phenotype: GITELMAN SYNDROME; GTLMNS
| 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.