PHYKPL was first reported in relation to autosomal recessive phosphohydroxylysinuria in 2013 (Veiga-da-Cunha M, et al., 2013, PMID: 23242558). The disease was first described by Dorland et al., 1990 (PMID: 2387074) from two patients with neurological problems, however these symptoms could be attributed to infectious causes in both cases. The two original cases were not available for molecular analysis of PHYKPL. A third case was subsequently identified and two unique missense variants were reported in this single case (PMID: 23242558). This case was not reported to have neurological problems but did have an Ehler-Danlos phenotype, thought to be unrelated to her metabolic defect. From the limited information available at this time it is difficult to determine if phosphohydroxylysinuria is a neurometabolic disease or an isolated metabolic abnormality. In addition to the single case, evidence supporting this gene-disease relationship includes the experimental data establishing the role of PHYKPL in the breakdown of 5-phosphohydroxy-L-lysine (PMID: 22241472) and a knockout mouse model from the International Mouse Phenotyping Consortium with limited relevant characterization. In summary, there is limited 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.
This gene-disease pair was previously approved by the Aminoacidopathy GCEP on 09/25/2020. It was reevaluated on 10/25/2023. As a result of this reevaluation, the classification remained Limited with no new evidence identified.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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