Submission Details

COG2 was first reported in relation to autosomal recessive Congenital Disorders of Glycosylation by Kodera H et al. in 2015 (PMID: 24784932). COG2 has only been reported in one additional proband since the first publication. Mutations in COG2 can lead to Congenital disorder of glycosylation (CDG), type IIq. CDGs result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor delay, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Clinical features of CDG-II caused by COG2 are characterized by normal presentation at birth, followed by progressive deterioration with postnatal microcephaly, developmental delay, intellectual disability, seizures, spastic quadriplegia, liver dysfunction, hypocupremia and hypoceruloplasminemia in the first year of life. No supporting segregation information is available, and the disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. This gene-disease relationship is supported by the biochemical function of COG2, the protein encoded by this gene is one of eight proteins (Cog1-8) that form a Golgi-localized complex (COG) required for normal Golgi morphology and function. LDLC CHO cells have shown the effects of COG2 and its restoration capabilities when transfected in the CHO cells (PMID: 21047787, 7962052). Coimmunoprecipitation experiments showed interaction with other proteins in the COG complex, specifically its interaction with COG1, COG3, and COG5(PMID: 11980916). Although additional genetic and experimental evidence is needed to establish a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. A classification of LIMITED was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on 2/7/24 (SOP Version 10)