ClinGen Dosage Sensitivity Curation Page

G6PC3

  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)

Haploinsufficiency phenotype comments:

Biallelic loss of function mutations in the G6PC3 gene causes Severe Congenical Neutropenia 4 (SCN4) and Dursun Syndrome. Both of them are autosomal recessive conditions supported by clinical observation as well as functional analyses. Lin et al. (2015) (PMID 25492228) functionally characterized 16 of the 19 known missense mutations using recombinant adenoviral vector-mediated expression system. Vectors carrying entire coding region of G6Pase-B (wild type, and mutants generated by PCR-directed mutagenesis) transfected the COS-1 cells. Phosphohydrolase activities and Western blot were carried out for the measurement of functional implications of mutants. Among 16 missense mutants tested, 14 showed a phosphoryhydrolase activity close to the background and two missense mutants showed an activity level at approximately 48-48% of wild type. Boztug et al (2012) (PMID 22050868) reported a 31 patients with syndromic severe congenital neuropenia. Biallelic mutations were found in 61% of the patients. one invariant splicing site mutation, c.218+1G>A, was detected and 5 truncating mutation were detected. These findings support a loss-of-function mutation mechanism.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for triplosensitivity phenotype
PubMed ID Description
N/A

Triplosensitivity phenotype comment:

no evidence for dosage pathogenicity