SLC6A8
Chr XXLRsolute carrier family 6 member 8
Also known as: CCDS1, CRT, CRT-1, CRT1, CRTR, CT1, CTR5
The encoded protein is a creatine transporter that mediates cellular uptake of creatine and supplies creatine to the brain via the blood-brain barrier. Mutations cause X-linked cerebral creatine deficiency syndrome 1, characterized by intellectual disability, speech delay, and seizures. This gene follows X-linked recessive inheritance and is highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 35 | 2 | 31 | 0 | 68 |
Likely Pathogenic | 25 | 15 | 4 | 0 | 44 |
VUS | 3 | 116 | 20 | 8 | 147 |
Likely Benign | 0 | 5 | 49 | 43 | 97 |
Benign | 0 | 1 | 4 | 0 | 5 |
| Total | 63 | 139 | 108 | 51 | 361 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC6A8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Optical Imaging in X-linked Disorders.
RECRUITINGRelevant Outcome Measures for Creatine Transporter Deficiency Patient
RECRUITINGExternal Resources
Links to major genomics databases and tools