HYKK

Inheritance Pattern: Unknown

Disease ID:MONDO:0017351

Submitter: ClinGen

The gene HYKK encodes aminoglycoside phosphotransferase domain-containing protein 1 (AGPHD1) and enzyme that catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine (Veiga-da-Cunha et al, 2012, PMID: 22241472). A questionable association between HYKK and hydroxylysinuria is listed in the International Classification of Inborn Metabolic Disorders (Ferreira et al, 2021, PMID: 33340416). Four probands with intellectual disability and hydroxylysinuria and/or hydroxylysinemia have been reported (Benson et al, 1969, PMID: 5765982; Parker et al, 1970, PMID: 4192000; Hoefnagel and Pomeroy, 1970, PMID: 4194840; Goodman et al, 1972, PMID: 5048993). While a deficiency of AGPHD1 has been hypothesized (Goodman et al, 1972, PMID: 5048993), to our knowledge, this has not been substantiated by experimental evidence. No reports describing individuals with pathogenic variants in HYKK and hydroxylysinuria and/or hydroxylysinemia were identified. However, individuals with biallelic variants in the gene that encode the next enzyme in the pathway, AGXT2L2, which breaks down phosphohydroxylysine have been reported (Veiga-da-Cunha et al, 2013, PMID: 23242558). Support for a potential gene-disease relationship between HYKK and hydroxylysinuria or hydrixylysinemia comes from the biochemical function of AGPHD1 which, as mentioned, catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine (Veiga-da-Cunha et al, 2012, PMID: 22241472). In summary, at the current time, there is insufficient genetic evidence to support a gene-disease relationship between HYKK and hydroxylysinuria or hydrixylysinemia. A classification of No Known Disease Relationship was approved by the Aminoacidopathy GCEP on July 14, 2023 (SOP v9).

Inheritance Pattern: AR

Disease ID:MONDO:0017351

Submitter: PanelApp Australia