CCS

Inheritance Pattern: Unknown

Disease ID:MONDO:0017762

Submitter: ClinGen

The *CCS* gene was first reported in relation to an autosomal recessive disorder of copper metabolism in 2012 (Huppker et al., PMID: 22508683). There has not been further evidence in the literature associating this gene with a specific phenotype. The proband described in this paper was a child from a consanguineous family who was found to have homozygous mutations in two genes: *SLC33A1* and *CCS*. His phenotype was mostly consistent with Huppke-Brendel syndrome (caused by bi-allelic pathogenic variants in *SLC33A1* with an unclear contribution from the missense variants in *CCS* reported in this paper. Currently, there are no OMIM phenotypes associated with this gene. A gene-disease relationship in the published case report was postulated by protein expression analysis through Western blotting on the proband’s fibroblasts, which showed that CCS protein levels were about 40% of those in controls, and that SOD1 enzyme activity was significantly decreased (Huppker et al., PMID: 22508683). This evidence was not scored in the present curation due to an alternative explanation for the described phenotype. In summary, there is limited evidence supporting the relationship between *CCS* and the autosomal recessive disorder of copper metabolism. This classification was approved by the ClinGen IEM GCEP on the meeting date [September, 27, 2024] (SOP Version 10).