| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mendeliome v1.3655 | CUL1 |
Sarah Milton gene: CUL1 was added gene: CUL1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CUL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CUL1 were set to PMID: 41189326 Phenotypes for gene: CUL1 were set to Neurodevelopmental disorder, MONDO:0700092, CUL1-related Review for gene: CUL1 was set to GREEN Added comment: CUL1 encodes Cullin 1 and is part of the SCF ubiquitin ligase complex which is involved in protein degradation and cell cycle progression. Other Cullin proteins have previously been implicated in neurodevelopmental disorders e.g. CUL3 PMID: 41189326 describes 4 probands with microcephaly (postnatal in 3 out of 4), severe ID, seizures (2/4) and variable dysmorphic features. Variant types include nonsense, missense and splice with proposed LOF mechanism. One individual inherited the variant from an affected mother with a slightly milder phenotype. All variants were very rare (1 het) or absent from gnomAD v4. CUL1 is under LOF constraint with very few NMD predicted variants in the population. The paper described supportive zebrafish studies showing knockout models had reduced forebrain proportion and abnormal growth. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.938 | KLHL9 |
Bryony Thompson changed review comment from: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3. Sources: Literature; to: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3. Ankle flexion contracture is reported in a mouse model, but there are other significant features present in the homozygous animals too - https://www.mousephenotype.org/data/genes/MGI:2180122 Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.938 | KLHL9 |
Bryony Thompson gene: KLHL9 was added gene: KLHL9 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KLHL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLHL9 were set to 20554658 Phenotypes for gene: KLHL9 were set to distal myopathy MONDO:0018949 Review for gene: KLHL9 was set to AMBER Added comment: A single German family reported in 2010, segregating a missense variant c.796T>C p.Leu95Phe. In vitro functional assays demonstrated the variant diminishes the binding of KLHL9 to Cul3. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6928 | CUL3 | Zornitza Stark Phenotypes for gene: CUL3 were changed from Pseudohypoaldosteronism, type IIE 614496; Intellectual disability; Autism; Seizures to Pseudohypoaldosteronism, type IIE 614496; Neurodevelopmental disorder with or without autism or seizures, MIM# 619239 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6927 | CUL3 | Zornitza Stark edited their review of gene: CUL3: Changed phenotypes: Pseudohypoaldosteronism, type IIE 614496, Neurodevelopmental disorder with or without autism or seizures 619239 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2785 | CUL3 | Zornitza Stark Publications for gene: CUL3 were set to 22495309; 22914163; 25363760; 27824329; 32341456 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2784 | CUL3 | Zornitza Stark edited their review of gene: CUL3: Changed publications: 22495309, 22914163, 25363760, 27824329, 32341456, 22266938 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2784 | CUL3 | Zornitza Stark Marked gene: CUL3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2784 | CUL3 | Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2784 | CUL3 | Zornitza Stark Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE 614496; Intellectual disability; Autism; Seizures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2783 | CUL3 | Zornitza Stark Publications for gene: CUL3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2782 | CUL3 | Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2781 | CUL3 | Zornitza Stark reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22495309, 22914163, 25363760, 27824329, 32341456; Phenotypes: Pseudohypoaldosteronism, type IIE 614496, Intellectual disability, Autism, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | CUL3 |
Zornitza Stark gene: CUL3 was added gene: CUL3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CUL3 was set to Unknown |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||