Renal Macrocystic Disease

Gene: ALG9

Green List (high evidence)

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

• PMID: 31395617, 32398770

I don't know

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: Literature

Created: 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

• 31395617
• 32398770