Disease relevance of SLC6A8

• High prevalence of SLC6A8 deficiency in X-linked mental retardation [1].
• Our data indicate that the frequency of SLC6A8 mutations in the XLMR population is close to that of CGG expansions in FMR1, the gene responsible for fragile-X syndrome [1].
• A human creatine transporter (hCRT-BS2M) cDNA clone was isolated from a human brainstem/spinal cord using a PCR and phage plaque hybridization based technique [2].
• The present study explored the regulation of SLC6A8 by the serum and glucocorticoid inducible kinase SGK1, a kinase upregulated during ischemia [3].
• Complement regulatory protein CD59 involves c-SRC related tyrosine phosphorylation of the creatine transporter in skeletal muscle during sepsis [4].

Psychiatry related information on SLC6A8

• Two female relatives who are heterozygous for the SLC6A8 mutation also exhibit mild mental retardation with behavior and learning problems [5].

High impact information on SLC6A8

• Comparative frequency of fragile-X (FMR1) and creatine transporter (SLC6A8) mutations in X-linked mental retardation [6].
• We have studied the prevalence of SLC6A8 mutations in a panel of 290 patients with nonsyndromic XLMR archived by the European XLMR Consortium. The full-length open reading frame and splice sites of the SLC6A8 gene were investigated by DNA sequence analysis [1].
• X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28 [5].
• Fibroblasts from the index patient contained a hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine uptake [7].
• We report the first X-linked creatine-deficiency syndrome caused by a defective creatine transporter [7].

Chemical compound and disease context of SLC6A8

• The ability to measure elevated creatine in urine makes it possible to diagnose SLC6A8 deficiency in male patients with mental retardation of unknown etiology [5].

Biological context of SLC6A8

• The pseudogene, psi SLC6A8, is exclusively expressed in the testis [8].
• The promoter regions of the SLC6A8, MSSK1 and CDM genes were found to be essentially unmethylated in all tissues, regardless of their relative expression level [8].
• Screening of a human hippocampal cDNA library with a rat creatine transporter cDNA-specific probe revealed two types of clones [9].
• The existence of an autosomal, testis-specific form of the human creatine transporter gene suggests that creatine transporter activity is critical for normal function of spermatazoa following meiosis [10].
• Translation of the CRT2 coding sequence reveals a new protein with regions of perfect homology with the CRT1 amino-acid sequence [9].

Anatomical context of SLC6A8

• Two monoclonal antibodies termed CT1 and CT2 define a cell surface oligosaccharide molecule expressed on restricted populations of murine lymphocytes [11].
• BACKGROUND: Myocellular creatine (Cr) uptake is predominantly governed by the creatine transporter (CreaT) and plays a pivotal role in skeletal muscle energy metabolism [4].
• At the rodent neuromuscular junction, the synaptic expression of the CT carbohydrate antigens is defined by the binding of two monoclonal antibodies, CT1 and CT2 [12].
• Fusion 3 transformed the atlas with 45 control points around the liver to CT1 and Fusion 4 transformed the atlas with 5 control points around the portal vein [13].
• Measurement of guanidinoacetate in body fluids may discriminate between the GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration) deficiencies [14].

Associations of SLC6A8 with chemical compounds

• The SLC6A8 deficient patients all show increased creatine/creatinine (Cr/Crn) ratio in urine demonstrating the importance of the Cr/Crn ratio as a pathognomonic marker of the SLC6A8 deficiency [15].
• Twenty-two amino acid residues from transmembrane domain 3 of the creatine transporter were replaced, one at a time, with cysteine [16].
• Here we show that the differential subsynaptic distribution of these antigens is due to a preference of CT1 for structures containing N-acetyl neuraminic acid (NeuAc) and a preference of CT2 for structures containing N-glycolyl neuraminic acid (NeuGc) [12].
• Although significant differences were found between CT1 and CT2, there were no interactions between the various DET conditions [17].
• Three genes were identified as being down regulated in the torsioned testis compared with controls: Control Testis genes 1, 2 and 3 (CT1, CT2 and CT3) [18].

Other interactions of SLC6A8

• GDI1 localized to GGA1pter and SLC6A8 to a mid-sized microchromosome [19].
• Two of the genes, SLC6A8 and MSSK1, are tissue-specifically expressed [8].
• X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome [7].
• Based on comparisons between genomic and cDNA sequence, both the Xq28 creatine transporter and DXS1357E genes are transcriptionally active [20].
• Since the creatine transporter has a prominent function in muscular physiology, it is a candidate gene for Barth syndrome and infantile cardiomyopathy mapped to Xq28 [21].

Analytical, diagnostic and therapeutic context of SLC6A8

• Assignment of the human creatine transporter type 2 (SLC6A10) to chromosome band 16p11.2 by in situ hybridization [22].
• Two estimates of carotid-vertebral artery transit times were measured: one time taken between the Q wave of the EKG to the commencement of the next succeeding impedance pulse-volume wave (CT1), and the other, this estimate together with the time to maximum point of the impedance wave (CT2) [23].
• Like other members of the interleukin-6 family of cytokines, CT-1 stimulates both the p42/p44 mitogen-activated protein kinase pathway and the Janus-activated kinase/signal transducers and activators of transcription pathway [24].
• Plasma CT-1 was determined by an enzyme-linked immunosorbent assay [25].
• Final values of CT-1 were inversely correlated (r = 0.534, P < 0.001) with the decrease in LVMI after treatment in all patients [25].

References