• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
SLC6A8 (HGNC:11055) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
solute carrier family 6 member 8
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
CRTR, CT1, CRT, CRT-1, CRT1
%HI
22.63(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.21(Read more about gnomAD LOEUF score)
Cytoband
Xq28
Genomic Coordinates
GRCh37/hg19: chrX:152953381-152962048 NCBI Ensembl UCSC
GRCh38/hg38: chrX:153687926-153696593 NCBI Ensembl UCSC
MANE Select Transcript
NM_005629.4 ENST00000253122.10 (Read more about MANE Select)
Function
Creatine:sodium symporter which mediates the uptake of creatine (PubMed:7953292, PubMed:7945388, PubMed:9882430, PubMed:17465020, PubMed:22644605, PubMed:25861866). Plays an important role in supplying creatine to the brain via the blood-brain barrier (By similarity). {ECO:0000250|UniProtKB:Q8VBW1, ECO:0000269|PubMed:17465020, ECO:0000269|PubMed:22644605, ECO:0000269|PubMed:25861866, ECO:0000269|PubMed:7945388, ECO:0000269|PubMed:7953292, ECO:0000269|PubMed:9882430}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-30394
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
11/10/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • creatine transporter deficiency Monarch
HI Evidence:
  • PUBMED: 29478817
    Joncquel-chevalier et al. (2018) did functional assessment of creatine transporter in 8 patients (4 males and 4 females) with splicing (N=3), small deletions (N=3) or missense variants (N=2) and equal number of controls, and proposed an easy, reliable and discriminative manner for exploring creatine transporter activity and disease variations.
  • PUBMED: 23644449
    Van de Kamp et al. (2013) did a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic variant in the creatine transporter gene (SLC6A8). A third of patients had a de novo variant in the SLC6A8 gene. The spectrum of variants in these patients are missense (N=26/85 families), in-frame (N=20/85 families), frame shift (N=15/80 families), nonsense (11/85 families), splicing (9/85 families), and multi-exon deletions (4 unrelated patients). The authors propose that missense variants with residual activity might be associated with a milder phenotype, and large deletions extending beyond the 3' end of the SLC6A8 gene are typically associated with a more severe phenotype.
  • PUBMED: 23660394
    Comeaux et al (2013) presented the biochemical and molecular testing results for 122 CCDS patients, with focus on 3 related genes: AGAT (N=20)and GAMT(N=33) for creatine biosynthesis disorders and SLC6A8 N=69, both males and females) for creatine transporter (CT1) deficiency. 26 patients (25 males and 1 female) were found to harbor deleterious mutations in the SLC6A8 gene, including nonsense, splicing, frameshift, partial/whole gene deletions.
HI Evidence Comments:
Loss of function mutations in SLC6A8 are responsible for creatine transport deficiency in males. Female carriers can be asymptomatic or may have milder phenotype including seizures and learning disabilities. Over 60 loss-of-function variants in this gene have been reported in the medical literature, including those mentioned in the publications listed here. Additional evidence includes: PMID: 20717164 Betsalel (2011): Multiple patients reported with splicing, nonsense, and frameshift variants. In this paper, the authors discuss the creation of an LOVD database for this gene. PMID: 16601897 Anselm (2006): Report of two patients with creatine transporter deficiency who had deletions of SLC6A8. Patient 1 had a de novo deletion of exons 8-13. Patient 2 had deletion of the entire gene, but the breakpoints were not well defined, and the deletion may have included adjacent genes. PMID: 11326334 Salomens (2001): First report of a patient with creatine transporter deficiency who had a nonsense mutation in SLC6A8. His mother and grandmother were carriers and had histories of learning disability.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence of triplosensitivity.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)