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Ataxia v2.131 PAK1 Sangavi Sivagnanasundram gene: PAK1 was added
gene: PAK1 was added to Ataxia. Sources: Literature
Mode of inheritance for gene: PAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK1 were set to 30290153
Phenotypes for gene: PAK1 were set to intellectual developmental disorder with macrocephaly, seizures, and speech delay, MONDO:0032568
Mode of pathogenicity for gene: PAK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PAK1 was set to GREEN
Added comment: PMID 30290153 reports 2 individuals from 2 families with de novo heterozygous PAK1 missense variants presenting with developmental delay, macrocephaly, seizures and ataxic gait. Patient fibroblast assays show gain‑of‑function effects (increased JNK/AKT phosphorylation, reduced dimerisation, enhanced filopodia) that are rescued by the PAK1 inhibitor FRAX486.
Ataxia is a prominent feature of this condition.
Sources: Literature