| Full gene name: | solute carrier family 6 (neurotransmitter transporter, creatine), member 8 |
|---|---|
| Entrez Gene ID: | 6535 |
| Location: | Xq28 |
| Synonyms: | CRTR, CT1, CRT |
| Type: | protein-coding |
SNPs given by the user that are near or inside this gene:
| SNP | Distance (bp) | Direction |
|---|---|---|
| rs3020789 | 60765 | upstream |
The protein encoded by this gene is a plasma membrane protein whose function is to transport creatine into and out of cells. Defects in this gene can result in X-linked creatine deficiency syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
| OMIM ID: | `OMIM ID 300036 `_ |
|---|
Allelic Variants (Selected Examples)
.0001 CREATINE DEFICIENCY SYNDROME, X-LINKED
In a male child diagnosed with mild mental retardation at age 6 years who had severe delay in both speech and expressive language function as well as creatine deficiency (300352), Salomons et al. (2001) found a hemizygous C-to-T transition in exon 11 of the SLC6A8 gene, resulting in an arg514-to-ter (R514X) mutation. Proton magnetic resonance spectroscopy of the child’s brain revealed absence of the creatine signal. However, creatine levels in urine and plasma were increased, and guanidinoacetate levels were normal. In 3 female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present to various extents. The 3 female relatives were heterozygous for this mutation.
.0002 CREATINE DEFICIENCY SYNDROME, X-LINKED
Hahn et al. (2002) described a family in which 5 males in a sibship of 10 had mental retardation with seizures associated with a defect in creatine metabolism (300352). Mutation analysis revealed an 1141G-C transversion at the -1 position of the exon 7/intron 7 splice junction of the SLC6A8 gene. This resulted in the gly381-to-arg missense change and interference with the 5-prime splice junction of intron 7. Subsequent biochemical analyses confirmed a defect in creatine metabolism in this family. The level of urinary creatine was substantially increased in affected male patients and creatine uptake in fibroblasts was decreased. Two sisters of the 5 affected males were heterozygous for the SLC6A8 mutation and exhibited mild mental retardation with behavior and learning problems.
.0003 CREATINE DEFICIENCY SYNDROME, X-LINKED
Bizzi et al. (2002) reported a child with creatine deficiency (300352) who had severe neurologic disturbances including seizures, behavioral problems, speech delay, and inability to engage in structured play. Proton magnetic resonance spectroscopic imaging showed absence of creatine in the whole brain, which was not corrected by creatine supplementation. Analysis of the SLC6A8 gene showed a hemizygous 3-bp deletion in exon 8, 1221delTTC, resulting in the deletion of a single phenylalanine at residue 408 in a conserved region of the protein. The patient’s mother was heterozygous for the mutation.
.0004 CREATINE DEFICIENCY SYNDROME, X-LINKED
In the index patient of a family with X-linked mental retardation, due to a defect in creatine metabolism (300352), Rosenberg et al. (2004) found an insertion of adenosine at cDNA position 950 in exon 6 of the SLC6A8 gene (950_951insA), resulting in a premature stop (tyr317 to stop, Y317X). The truncated mutant protein was predicted to lack 319 C-terminal residues, including transmembrane domains VII through XII, and to be unstable and/or inappropriately folded and therefore completely inactive.
.0005 CREATINE DEFICIENCY SYNDROME, X-LINKED
In the index patient of a family with X-linked mental retardation due to a defect in creatine metabolism (300352), Rosenberg et al. (2004) found a G-to-A transition at cDNA position 259 in exon 1 of the SLC6A8 gene that gave rise to a gly87-to-arg (G87R) amino acid substitution. This mutation changes one of 3 glycines that make up a short repeat between transmembrane domains I and II, in a small intracellular loop that is highly conserved among all known creatine transporters and within the neurotransmitter transporter family SLC6.
.0006 CREATINE DEFICIENCY SYNDROME, X-LINKED
In a male patient with X-linked creatine deficiency syndrome and severe mental retardation (300352), Schiaffino et al. (2005) identified an A-to-G transition in intron 1 of the SLC6A8 gene, resulting in skipping of the first 21 amino acids of exon 2. These residues form the second transmembrane domain, which is highly conserved.
.0007 CREATINE DEFICIENCY SYNDROME, X-LINKED
In 2 brothers with X-linked creatine deficiency syndrome and mental retardation (300352), Rosenberg et al. (2004) identified a 1011C-G transversion, resulting in a cys337-to-trp (C337W) substitution in the highly conserved intracellular loop between transmembrane domains VI and VII. In the urine of the 2 patients, an increased creatine:creatinine ratio was found, which is a biochemical hallmark of SLC6A8 deficiency. The sister of the patients was a carrier of the C337W mutation.
.0008 CREATINE DEFICIENCY SYNDROME, X-LINKED
In a 4-year-old boy with creatine deficiency syndrome and severe mental retardation (300352), Lion-Francois et al. (2006) identified a 395G-T transversion in the SLC6A8 gene, resulting in a gly132-to-val (G132V) substitution. The patient had delayed onset of walking and autistic behavior.
.0009 CREATINE DEFICIENCY SYNDROME, X-LINKED
In a 14-year-old boy with creatine deficiency syndrome and severe mental retardation (300352), Lion-Francois et al. (2006) identified a 1473C-G transversion in the SLC6A8 gene, resulting in a cys491-to-trp (C491W) substitution. The patient had delayed onset of walking, seizures, and autistic features. Brain imaging showed atrophy of the left caudate and hippocampus and a thin corpus callosum.
.0010 CREATINE DEFICIENCY SYNDROME, X-LINKED
In a 6-year-old boy with creatine deficiency syndrome (300352), Clark et al. (2006) identified a hemizygous 3-bp deletion (1006delAAC) in exon 6 of the SLC6A8 gene, resulting in a deletion of a highly conserved residue asn336. The patient had moderate mental retardation, attention deficit-hyperactivity disorder, microcephaly, and tall stature.
Battini et al. (2007) identified the 1006delAAC mutation in a 9.5-year-old Italian boy with mental retardation and verbal dyspraxia. He had delayed psychomotor development, hypotonia, seizures, and severe language deficit with oral-motor dyspraxia, irritability, and temper tantrums. Detailed language evaluation showed problems in picture naming and phonetics, whereas receptive vocabulary was less severely affected. Social interaction was good despite the severe expressive limitation. Battini et al. (2007) noted that the phenotype in their patient was different than that reported by Clark et al. (2006).
No pathways found linked to this gene.
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