Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.10 (
IKK
)
4,900
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Autosomal-recessive inheritance accounts for nearly 25% of nonsyndromic mental retardation (MR), but the extreme heterogeneity of such conditions markedly hampers gene identification. Combining autozygosity mapping and RNA expression profiling in a consanguineous Tunisian family of three MR children with mild microcephaly and white-matter abnormalities identified the
TRAPPC9
gene, which encodes a NF-kappaB-inducing kinase (NIK) and
IkappaB kinase
complex beta (IKK-beta) binding protein, as a likely candidate. Sequencing analysis revealed a nonsense variant (c.1708C>T [p.R570X]) within exon 9 of this gene that is responsible for an undetectable level of
TRAPPC9
protein in patient skin fibroblasts. Moreover, TNF-alpha stimulation assays showed a defect in IkBalpha degradation, suggesting impaired NF-kappaB signaling in patient cells. This study provides evidence of an NF-kappaB signaling defect in isolated MR.
...
PMID:Combination of linkage mapping and microarray-expression analysis identifies NF-kappaB signaling defect as a cause of autosomal-recessive mental retardation. 2000 64
