RAB39B was first reported in relation to X-linked intellectual disability in 2010 (Giannandrea et al., PMID: 20159109) and was subsequently reported in relation to X-linked early-onset parkinsonism-intellectual disability syndrome in 2014 (Wilson et al., PMID: 25434005). RAB39B encodes a protein involved in vesicular trafficking. The disorder is characterized by intellectual disability, early-onset parkinsonism, macrocephaly, and seizures.
Six variants (nonsense, frameshift, splice, and missense) that have been reported in 7 probands in 5 publications (PMIDs: 20159109, 21076407, 25434005, 27066548, 28851564) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by experimental evidence in mouse hippocampal neurons (PMID: 25784538).
In summary, there is definitive evidence supporting the relationship between RAB39B and X-linked early-onset parkinsonism-intellectual disability syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 4, 2018 (SOP Version 5). As of July 2022, this record underwent administrative updates to include an evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added.
RAB39B was first reported in relation to X-linked intellectual disability in 2010 (Giannandrea et al., PMID: 20159109) and was subsequently reported in relation to X-linked early-onset parkinsonism-intellectual disability syndrome in 2014 (Wilson et al., PMID: 25434005). RAB39B encodes a protein involved in vesicular trafficking. The disorder is characterized by intellectual disability, early-onset parkinsonism, macrocephaly, and seizures.
Six variants (nonsense, frameshift, splice, and missense) that have been reported in 7 probands in 5 publications (PMIDs: 20159109, 21076407, 25434005, 27066548, 28851564) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by experimental evidence in mouse hippocampal neurons (PMIDs: 20159109, 25784538).
In summary, there is definitive evidence supporting the relationship between RAB39B and X-linked early-onset parkinsonism-intellectual disability syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 4, 2018 (SOP Version 5). As of July 2022, this record underwent administrative updates to include an evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added.
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