Disease relevance of IL1RAPL1

• We report the identification and characterization of a homologue of the IL1RAPL transcript which is responsible for a form of X-linked mental retardation (MRX34) [1].

Psychiatry related information on IL1RAPL1

• The literature contains multiple reports of patients with non-syndromic mental retardation in association with an Xp22.1-Xp21.3 microdeletion of a marker which lies within the IL1RAPL1 gene [2].

High impact information on IL1RAPL1

• 3. Because carrier females with microdeletion in the IL1RAPL gene do not present any abnormal phenotype, we focused on the Xq breakpoint [3].
• Previously, human genetics-based approaches allowed us to show that mutations in the IL-1 receptor accessory protein-like gene (IL1RAPL) are responsible for a non-specific form of X-linked mental retardation [4].
• Taken together, our data suggest that IL1RAPL may regulate calcium-dependent exocytosis and provide insight into the understanding of physiopathological mechanisms underlying cognitive impairment resulting from IL1RAPL dysfunction [4].
• Remarkably, although NCS-1 and its non-mammalian homologue, frequenin, are members of a highly conserved EF-hand Ca(2+) binding protein family, our data show that IL1RAPL interacts only with NCS-1 through its specific C-terminal domain [4].
• The functional relevance of IL1RAPL activity was further supported by the inhibitory effect on exocytosis in PC12 cells overexpressing IL1RAPL [4].

Biological context of IL1RAPL1

• Our data are consistent with the association of IL1RAPL1 gene deletion and MR in the majority of patients with cGKD and deletions extending telomeric from DAX1 [5].
• Further investigations by FISH showed that the IL1RAPL1 gene at Xp21.3 was disrupted by the X chromosome inversion and therefore its inactivation may be related to the mental retardation observed in our patients [6].
• MRX21 is the first extended MRX family with a point mutation in IL1RAPL1 and the second with a stop mutation, which had been previously found only in a small family [7].

Other interactions of IL1RAPL1

• Both IL1RAPL1 and IL1RAPL2 have novel C-terminal sequences not present in other related proteins, and are encoded by very large genes [2].
• Our results showed that nearly all patients with deletions involving DAX1, but not DMD, had MR if IL1RAPL1 was deleted [5].
• The genes have been named according to their structural features: TIGIRR-1 (three immunoglobulin domain-containing IL-1 receptor-related) and TIGIRR-2 [8].
• No mutations were found in the presented family for two known MRX genes mapping to this interval, ARX and IL1RAPL-1 [9].

References