Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In view of important neurobiological functions of the cell adhesion molecule contactin-6 (Cntn6) that have emerged from studies on null-mutant mice and autism spectrum disorders patients, we set out to examine pathways underlying functions of Cntn6 using a proteomics approach. We identified the cell adhesion GPCR latrophilin-1 (Lphn1, a.k.a. CIRL1/CL, ADGRL1) as a binding partner for Cntn6 forming together a heteromeric cis-complex. Lphn1 expression in cultured neurons caused reduction in neurite outgrowth and increase in apoptosis, which was rescued by coexpression of Cntn6. In cultured neurons derived from Cntn6-/- mice, Lphn1 knockdown reduced apoptosis, suggesting that the observed apoptosis was Lphn1-dependent. In line with these data, the number of apoptotic cells was increased in the cortex of Cntn6-/- mice compared to wild-type littermate controls. These results show that Cntn6 can modulate the activity of Lphn1 by direct binding and suggests that Cntn6 may prevent apoptosis thereby impinging on neurodevelopment.
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PMID:Association of Cell Adhesion Molecules Contactin-6 and Latrophilin-1 Regulates Neuronal Apoptosis. 2810 2

Recent research revealed that autism spectrum disorders (ASD) and cancer may share common genetic architecture, with evidence first reported with the PTEN gene. There are approximately 800 autism genes and 3500 genes associated with cancer. The VarElect phenotype program was chosen to identify genes jointly associated with both conditions based on genomic information stored in GeneCards. In total, 138 overlapping genes were then profiled with GeneAnalytics, an analysis pathway enrichment tool utilizing existing gene datasets to identify shared pathways, mechanisms, and phenotypes. Profiling the shared gene data identified seven significantly associated diseases of 2310 matched disease entities with factors implicated in shared pathology of ASD and cancer. These included 371 super-pathways of 455 matched entities reflecting major cell-signaling pathways and metabolic disturbances (e.g., CREB, AKT, GPCR); 153 gene ontology (GO) biological processes of 226 matched processes; 41 GO molecular functions of 78 matched functions; and 145 phenotypes of 232 matched phenotypes. The entries were scored and ranked using a matching algorithm that takes into consideration genomic expression, sequencing, and microarray datasets with cell or tissue specificity. Shared mechanisms may lead to the identification of a common pathology and a better understanding of causation with potential treatment options to lessen the severity of ASD-related symptoms in those affected.
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PMID:GeneAnalytics Pathways and Profiling of Shared Autism and Cancer Genes. 3086 37

GPRASP (GPCR-associated sorting protein)/ARMCX (ARMadillo repeat-Containing proteins on the X chromosome) family is composed of 10 proteins, which genes are located on a small locus of the X chromosome except one. They possess at least two armadillo-like repeats on their carboxyl-terminal homologous sequence, but they can be subdivided on specific sequence features. Subfamily 1 (GPRASP1, GPRASP2, GPRASP3, ARMCX4 and ARMCX5) displays additional repeated motifs while a mitochondrial targeting transmembrane domain is present in subfamily 2 (ARMC10, ARMCX1, ARMCX2, ARMCX3 and ARMCX6). Although their roles are not yet fully understood, the recent identification of several interacting partners have shed new light on the processes in which GPRASP/ARMCX proteins are implicated. Among the interacting partners of proteins from subfamily 1, many are GPCRs. GPRASP1 binds trafficking proteins such as Beclin2 and the Dysbindin-HRS-Gas complex to participate in GPCR post-endocytic sorting. Moreover, in vitro as well as in vivo experiments indicate that GPRASP1 is a critical player in the adaptive responses related to chronic treatments with GPCR agonists. GPRASP2 seems to play a key role in the signalling of the hedgehog pathway in the primary cilium through a Smoothened-GPRASP2-Pifo complex. Identified small compound inhibitors of this complex could treat drug-resistant Smoothened derived cancer forms. Deletion of GPRASP2 in mice causes neurodevelopmental alteration and affects mGluR5 regulation, reflected by autism-like behaviour. Several members of subfamily 2, in complex with TRAK2 and MIRO, are involved in the trafficking of mitochondria in axons and on the regulation of their size and division, influencing the cell cycle. The essential role of GPRASP/ARMCX proteins in the cellular physiology is supported by human cases of deletions, causing male neonatal lethality by pulmonary delayed development, dysmorphic face and psychiatric and intellectual impacts in females.
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PMID:GPRASP/ARMCX protein family: potential involvement in health and diseases revealed by their novel interacting partners. 3326 63