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| Skeletal dysplasia v1.2 | ID4 downstream regulatory region | Sarah Milton Classified Region: ID4 downstream regulatory region as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.2 | ID4 downstream regulatory region | Sarah Milton Region: id4 downstream regulatory region has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.1 | ID4 downstream regulatory region |
Sarah Milton Region: ID4 downstream regulatory region was added Region: ID4 downstream regulatory region was added to Skeletal dysplasia. Sources: Literature regulatory region tags were added to Region: ID4 downstream regulatory region. Mode of inheritance for Region: ID4 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for Region: ID4 downstream regulatory region were set to 42069959; 26032025; 24628666 Phenotypes for Region: ID4 downstream regulatory region were set to Mesomelic dysplasia, Savarirayan type, MIM#605274 Review for Region: ID4 downstream regulatory region was set to GREEN Added comment: ID4 encodes inhibitor of DNA binding 4 (ID4) protein which modulates gene expression through binding to and inhibiting bHLH transcription factors. It is involved in regulation of cellular growth, senescence, differentiation and apoptosis. It is known to be expressed in the developing limb bud. PMID: 42069959, 26032025, 24628666 report a total of 5 individuals with de novo structural variants (deletions of around 2mb in size and one inversion) affecting the region downstream of ID4 at 6p22.3. The clinical presentation of these individuals was that of Mesomelic dysplasia, Savarirayan type characterised by mesomelic shortening of the lower limbs with the upper limbs affected in some individuals and specific radiographic findings. The deletions encompassed 4 protein coding genes none of which are involved in skeletal development. As such it was hypothesized these structural variants disrupt TADs resulting in ID4 dysregulation, bringing the gene in closer proximity to a cluster of enhancers downstream. Deletions involving the ID4 gene did not recapitulate the phenotype, as such, dysregulated expression as opposed to loss of function is thought to be the mechanism. There are no equivalent deletions in population databases (gnomAD/DGV gold) Hi-C studies have been performed however functional studies using luciferase reporter assays/qPCR of ID4 have not yet been published. Note: Coordinates used for this entry are that of the smallest reported deletion. Sources: Literature |
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| Skeletal dysplasia v0.455 | Sarah Milton Copied Region ID4 downstream regulatory region from panel Mendeliome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.455 | ID4 downstream regulatory region |
Sarah Milton Region: ID4 downstream regulatory region was added Region: ID4 downstream regulatory region was added to Skeletal dysplasia. Sources: Expert Review Green,Literature regulatory region tags were added to Region: ID4 downstream regulatory region. Mode of inheritance for Region: ID4 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for Region: ID4 downstream regulatory region were set to 42069959; 26032025; 24628666 Phenotypes for Region: ID4 downstream regulatory region were set to Mesomelic dysplasia, Savarirayan type, MIM#605274 |
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