Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: GCC2

I don't know

Comment on list classification: As reviewed by Boaz Palterer, there are 2 unrelated individuals reported in literature with biallelic variants in GCC2 and recurrent viral infections, with demonstrated reduced natural killer cell function (PMID:39813120). Hence, this gene should be rated Amber for Primary immunodeficiency or monogenic inflammatory bowel disease, until more evidence emerges.
This gene is not yet associated with a phenotype in OMIM (accessed 31st Oct 2025).

Created: 31 Oct 2025, 2:16 p.m. | Last Modified: 31 Oct 2025, 2:19 p.m.

Panel Version: 8.70

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
NK cell deficiency; recurrent viral infections; immunodeficiency

Publications

• 39813120

Red List (low evidence)

Pedroza et al. described 2 patients in two separate kindreds with compound heterozygous GCC2 mutations presenting in childhood with recurrent viral infections, normal NK cell numbers but reduced NK cell function.
During NK cell activation, lytic granules (LGs) converge to the MTOC, enabling precision in cytotoxicity. Pedroza et al. demonstrate that GCC2 maintains convergence via tethering LGs to the Golgi. Absence of GCC2 leads to LG dispersion, non-directed degranulation, and bystander killing, and biallelic missense variants result in human NK cell deficiency.
Sources: Literature

Created: 7 Apr 2025, 7:23 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
NK cell deficiency; recurrent viral infections; immunodeficiency

Publications

• 39813120