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| Intellectual disability syndromic and non-syndromic v2.107 | LDB1 |
chirag patel gene: LDB1 was added gene: LDB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LDB1 were set to Neurodevelopmental disorder, MONDO:0700092, LDB1-related Review for gene: LDB1 was set to AMBER Added comment: ESHG 2026 16 unrelated individuals with 16 different rare heterozygous de novo variants (missense, nonsense, frameshift, gene deletions) in the LDB1 gene. Eleven variants affect the whole gene or the N-terminal dimerization domain and 5 variants affect only the C-terminus. All individuals presented with developmental delay and behaviour issues, but individuals with C-terminal variants also presented with ventriculomegaly. LDB1 encodes transcriptional regulator protein LIM-domain-binding protein 1, which plays an important role in neurogenesis. In vitro assays showed the N-terminal missense variants disrupted homodimerization of LDB1 (likely leading to a loss of function) but the C-terminal variants impaired interaction with the essential partner LHX2 (in a dominant-negative fashion). Toxicity of overexpressed human LDB1 in Drosophila was not seen for N-terminal missense variants but was exacerbated by C-terminal variants. Phenotypes associated with LDB1/chi loss in Drosophila were a) rescued by overexpression of wild-type LDB1, b) not rescued by N-terminal missense variants, and c) worsened by C-terminal variants. This suggests 2 distinct pathomechanisms of LDB1-related NDDs. Sources: Other |
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| Intellectual disability syndromic and non-syndromic v2.0 | LHX2 | Gene migrated from ENSG00000106689 to ENSG00000106689 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5225 | LHX2 | Zornitza Stark Marked gene: LHX2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5225 | LHX2 | Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5225 | LHX2 | Zornitza Stark Publications for gene: LHX2 were set to PMID: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5224 | LHX2 | Zornitza Stark Phenotypes for gene: LHX2 were changed from to Neurodevelopmental disorder (MONDO: 0700092) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5223 | LHX2 | Zornitza Stark Classified gene: LHX2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5223 | LHX2 | Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5220 | LHX2 | Manny Jacobs reviewed gene: LHX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37057675; Phenotypes: Neurodevelopmental disorder (MONDO: 0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5219 | LHX2 |
Manny Jacobs gene: LHX2 was added gene: LHX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LHX2 were set to PMID: |
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