Disease relevance of OPHN1

• Notably, OPHN1 mutations have been previously reported as a rare cause of non-syndromic X-linked mental retardation [1].
• In addition, identification of OPHN1 as a further gene associated with epileptic seizures will help to unravel aetiologic factors of epilepsy [1].
• Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia [2].
• OPHN1 and RPN II appeared to be differentially expressed in gastric cancers exhibiting LVI [3].
• Significant overexpression of oligophrenin-1 in colorectal tumors detected by cDNA microarray analysis [4].
• In 2014 was formed as a patient advocacy and disease community group .

Psychiatry related information on OPHN1

• OPHN1 was screened for mutations in 164 subjects with non-specific mental retardation [5].

High impact information on OPHN1

• Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation [6].
• At the cellular level OPHN1 is expressed in both glial and neuronal cells where it colocalizes with actin, notably at the tip of growing neurites [7].
• Evidence that a major site of expression of the RHO-GTPASE activating protein, oligophrenin-1, is peripheral myelin [8].
• Greater amounts of the full length oligophrenin-1 protein occurred in the sciatic nerve of adult rats, compared with P2 rats, which reflects the development of myelination [8].
• Oligophrenin-1 immunoreactivity was found in glial cells forming myelin sheaths in the vagus nerve, sciatic nerve and dorsal roots of guinea-pig, rat and human, in chromaffin cells of the adrenal medulla, and in chromaffin cells associated with sympathetic ganglia [8].

Chemical compound and disease context of OPHN1

• Four genes mutated in families with mental retardation encode proteins known as Rho guanine nucleotide exchange factor 6, oligophrenin-1, p21-activated kinase, and guanine dissociation inhibitor 1 [9].

Biological context of OPHN1

• Knowledge of the genomic structure of the OPHN1 gene, which spans at least 500 kb and consists of 25 exons, will facilitate the search for additional mutations in OPHN1 [5].
• The structure of the gene encoding the OPHN1 protein was determined by isolation of genomic DNA clones from the human cosmid library [5].
• Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families [10].
• The translated amino acid sequence was 99% identical to the published human oligophrenin-1 sequence [8].
• JAR cell migration in response to OPN-1 was accompanied by a rapid rearrangement of actin filaments to the cellular membrane [11].

Anatomical context of OPHN1

• These findings demonstrate that a major site of oligophrenin-1 expression is peripheral myelin [8].
• By RT-PCR, oligophrenin-1 was expressed in tumors and tumor-adjacent tissue, whereas meningioma and corpus callosum were negative [12].
• The highly phosphorylated human milk form of OPN (OPN-1) strongly triggered migration in all three cell lines, whereas the less phosphorylated variants, OPN-2a and OPN-2b, failed to stimulate migration [11].

Associations of OPHN1 with chemical compounds

• Activation was blocked completely by rapamycin and LY294002, thus demonstrating that OPN-1-stimulated migration occurs through mTOR and PI3K pathways, respectively [11].

Regulatory relationships of OPHN1

• Using broad spectrum protein kinase profiling, we identified p70 S6 kinase as a major signal transduction pathway activated by OPN-1 during the migratory response in JAR cells [11].

Other interactions of OPHN1

• A visual physical map of 1.2 Mb was constructed which spans the oligophrenin-1 gene and the androgen receptor gene [2].
• Sequencing and BLAST analysis revealed that seven of the genes were known genes:ADP-ribosylation factor 4, Cytochrome oxidase subunit II, Ss-A/Ro ribonucleoprtein autoantigen 60kd subunit,ribosomal protein S13, galaectin-8 gene, oligophrenin 1 mRNA, ribosomal protein L23 mRNA; thirteen of the genes were unknown genes [13].

Analytical, diagnostic and therapeutic context of OPHN1

• Since little is known about the cellular localization of oligophrenin-1 in central and peripheral neurons, we investigated its expression by RT-PCR and immunochemical analysis [8].
• Using cDNA microarrays, we found evidence that oligophrenin-1 is strongly up-regulated in colorectal tumors [4].

References