Renal Macrocystic Disease
Gene: ALG9
CLINGEN assessed as MODERATE (2020)
Evidence supporting this gene-disease relationship includes case-level genetic data and experimental data. Variants in this gene have been reported in 10 probands with clear evidence of cystic kidney disease in 2 publications (PMID: 31395617; PMID: 32398770). 4 patients were reported to not display multiple kidney cysts and 3 had insufficient clinical data available for assessment (PMID: 31395617), consistent with ALG9-associated ADPKD having variable penetrance and expressivity. This gene-disease association is supported by in vitro functional assays showing reduced maturation of polycystin 1 in ALG9 null cells (PMID: 31395617). In summary, there is moderate evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.Created: 25 Nov 2022, 2:38 a.m. | Last Modified: 25 Nov 2022, 2:38 a.m.
Panel Version: 0.55
Phenotypes
Polycystic kidney disease
Publications
Additional individual reported in PMID 30676690 as part of a large cohort.Created: 26 Aug 2020, 9:27 p.m. | Last Modified: 26 Aug 2020, 9:27 p.m.
Panel Version: 0.37
Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. Bi-allelic variants cause CDG: kidney cysts reported as part of phenotype but note this is generally a severe multi-system disorder. It is unclear at present whether the mechanism is the same for both. It may be that bi-allelic LOF is perinatal lethal, hence CDG carriers for missense variants are less likely to manifest renal cysts.
Sources: LiteratureCreated: 27 May 2020, 9:49 p.m. | Last Modified: 26 Aug 2020, 9:35 p.m.
Panel Version: 0.37
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease
Publications
Phenotypes for gene: ALG9 were changed from Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease to Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease; ALG9-associated autosomal dominant polycystic kidney disease MONDO:0700000
Gene: alg9 has been classified as Green List (High Evidence).
Gene: alg9 has been classified as Amber List (Moderate Evidence).
Gene: alg9 has been classified as Amber List (Moderate Evidence).
gene: ALG9 was added gene: ALG9 was added to Renal Macrocystic Disease. Sources: Literature Mode of inheritance for gene: ALG9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ALG9 were set to 31395617 Phenotypes for gene: ALG9 were set to Congenital disorder of glycosylation, type Il, MIM# 608776; Gillessen-Kaesbach-Nishimura syndrome, MIM#263210; Polycystic kidney disease Review for gene: ALG9 was set to AMBER