Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

SLC6A8

contributors: mct/pgu - updated : 13-06-2018

HGNC name	solute carrier family 6 (neurotransmitter transporter, creatine), member 8
HGNC id	11055

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CRTRD creatine deficiency syndrome
Location	Xq28      Physical location : 152.953.751 - 152.962.048
Synonym name	sodium- and chloride-dependent creatine transporter 1
	creatine transporter 1
Synonym symbol(s)	CRTR, CTSP, CT1, CRTRD, MGC87396, CRT, CCDS1, CTR5, Creat

DNA

TYPE	functioning gene
STRUCTURE	8.30 kb     13 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map

see L1CAM

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005629 13 - 3580 NP_005620 70.5 635 - - 18515020 NM_001142805 13 splicing 3550 NP_001136277 - 625 - - 18515020 also known as SLC6A8B NM_001142806 13 splicing 3129 NP_001136278 58.3 520 predominantly found in human tissues with a high energy requirement such as brain, kidney, heart, small intestines and skeletal muscle - 18515020 also known SLC6A8C prediction of a truncated protein identical to the variant 1, comprising the five last C-terminal transmembrane domains

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Nervous brain limbic system hippocampus dentate gyrus highly Homo sapiens   brain forebrain cerebral cortex   highly Homo sapiens Visual eye lens     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   predominantly Homo sapiens Nervous central     predominantly

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Nervous neuron Nervous pyramidal cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

twelve transmembrane segments

HOMOLOGY

interspecies	homolog to C.elegans T03F7.1
	homolog to murine Slc6a8

Homologene

FAMILY	sodium neurotransmitter symporter family
	SLC6A8 subfamily

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
text	presence of a functional SLC6A8 in the axon terminal membrane that may serve to recapture the creatine released during the synapsis

basic FUNCTION	Na+ (and Cl-) dependent plasma membrane transporter required for the uptake of creatine
	playing an essential role in the storage and transmission of phosphate-bound energy
	in most brain regions, may be transporting guanidinoacetate from GATM/GAMT-expressing cells to allow creatine synthesis
	. is an important metabolic regulator controlling antitumor T cell immunity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with SGK1, SGK3 (increase SLC6A8 activity by increasing the maximal transport rate of the carrier)
	Klotho protein up-regulates the activity of creatine transporter SLC6A8 by stabilizing the carrier protein in the cell membrane, an effect requiring beta-glucuronidase activity of KL protein
	both, STK39 and OSR1, are negative regulators of the creatine transporter SLC6A8
	JAK3 is a powerful negative regulator of SLC6A8

cell & other

REGULATION

activated by

FRAP1

ASSOCIATED DISORDERS

corresponding disease(s)

CRTRD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in astrocytes around the blood-brain barrier limits the brain capacity to import creatine from the periphery, and suggests that the CNS has to rely mainly on endogenous creatine synthesis through GATM/GAMT constitutional     --low   depletion of intracellular creatine by ablation of the creatine transporter SLC6A8 altered macrophage-mediated immune responses constitutional     --low   in dopaminergic neurons causes hyperactivity while sparing motor function

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     potential of creatine supplementation to improve T cell-based cancer immunotherapies cancer lung   expected to become a molecular target for NSCLC treatment

ANIMAL & CELL MODELS