SLC6A8

solute carrier family 6 member 8, the group of Solute carrier family 6

Basic information

Region (hg38): X:153687925-153696588

Links

ENSG00000130821 ∙ NCBI:6535 ∙ OMIM:300036 ∙ HGNC:11055 ∙ Uniprot:P48029 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• creatine transporter deficiency (Definitive), mode of inheritance: XLR
• creatine transporter deficiency (Strong), mode of inheritance: XL
• creatine transporter deficiency (Supportive), mode of inheritance: XL
• creatine transporter deficiency (Definitive), mode of inheritance: XL
• creatine transporter deficiency (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Creatine deficiency syndrome 1	XL	Biochemical	Medical treatment (with oral creatine, arginine, and/or glycine supplementation) has been described as beneficial in some patients, as measured by increased cerebral creatine or improved clinical findings	Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	11261517; 11326334; 11898126; 12210795; 12889669; 15154114; 16738945; 17101918; 18569740; 19188083; 20301745; 20501887; 20528887; 20717164; 20846889; 21144783; 21556832; 21660517; 22644605; 22281021; 23660394; 23644449; 24953403

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A8 gene.

• Creatine transporter deficiency (757 variants)
• not provided (210 variants)
• not specified (94 variants)
• Inborn genetic diseases (68 variants)
• Creatine deficiency syndrome 1 (51 variants)
• Intellectual disability (4 variants)
• - (2 variants)
• SLC6A8-related condition (1 variants)
• Low-set ears;Abnormal facial shape;Seizure;Intellectual disability (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	258	17	282
missense	4	19	168	28	13	232
nonsense	22	4	1			27
start loss						0
frameshift	35	15	2			52
inframe indel	3	6	5	1		15
splice donor/acceptor (+/-2bp)	9	6	1		1	17
splice region	1	1	16	56	6	80
non coding			5	109	18	132
Total	73	50	189	396	49

Highest pathogenic variant AF is 0.00000914

Variants in SLC6A8

This is a list of pathogenic ClinVar variants found in the SLC6A8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-153688564-C-T		not specified	Likely benign (Jul 01, 2016)
X-153688569-G-T			Uncertain significance (Jan 12, 2022)
X-153688569-GA-G		not specified	Likely benign (Dec 28, 2017)
X-153688570-A-G		not specified • Creatine transporter deficiency • Creatine deficiency syndrome 1 • Inborn genetic diseases • SLC6A8-related disorder	Benign (Nov 29, 2023)
X-153688575-A-G		Creatine transporter deficiency	Uncertain significance (Mar 23, 2023)
X-153688579-CGAA-C		Creatine transporter deficiency	Uncertain significance (Sep 01, 2022)
X-153688580-G-A		Creatine transporter deficiency	Likely benign (Jun 09, 2023)
X-153688581-A-G			Uncertain significance (Jun 23, 2023)
X-153688583-G-A		Creatine transporter deficiency	Likely benign (Feb 27, 2022)
X-153688585-A-G		Creatine transporter deficiency	Uncertain significance (Jan 11, 2024)
X-153688586-G-A		Creatine transporter deficiency	Likely benign (May 21, 2023)
X-153688586-G-C		Creatine transporter deficiency	Uncertain significance (Jan 03, 2024)
X-153688589-C-A			Uncertain significance (Sep 02, 2020)
X-153688592-C-G		Creatine transporter deficiency	Likely benign (Nov 05, 2021)
X-153688592-C-T		Creatine transporter deficiency	Likely benign (Jun 13, 2022)
X-153688599-G-T		Creatine transporter deficiency	Uncertain significance (Jun 04, 2022)
X-153688600-G-T		Creatine transporter deficiency • Creatine deficiency syndrome 1	Likely benign (Jun 06, 2022)
X-153688604-C-T		not specified • Creatine transporter deficiency	Likely benign (May 17, 2023)
X-153688613-G-A		Creatine transporter deficiency	Likely benign (Aug 01, 2019)
X-153688616-C-T		Creatine transporter deficiency	Likely benign (Nov 27, 2023)
X-153688622-C-A		Creatine transporter deficiency	Uncertain significance (Jun 06, 2022)
X-153688622-C-T		Creatine transporter deficiency	Likely benign (Sep 19, 2021)
X-153688623-GAGA-G			Likely benign (Apr 01, 2019)
X-153688625-G-C		Creatine transporter deficiency	Uncertain significance (Jun 13, 2022)
X-153688627-AGAAGGGCCCCCTCATCGCGCCCGGGCCCGACGGGGCCCCGGCCAAGGGCGACGGCCCCGTGGGCCTGGGGACACCCGGCGGCCG-CCGTGT		Creatine transporter deficiency	Likely pathogenic (Jun 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A8	protein_coding	protein_coding	ENST00000253122	13	8495

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00222	125403	0	2	125405	0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.05	118	255	0.463	0.0000214	4096
Missense in Polyphen		21	108.04	0.19438		1734
Synonymous	-1.17	130	114	1.14	0.0000106	1273
Loss of Function	4.18	1	22.3	0.0449	0.00000150	348

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000731	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000124	0.00000882
Middle Eastern	0.0000731	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the uptake of creatine in muscles and brain.
• Pathway: Nuclear Receptors Meta-Pathway;NRF2 pathway;Metabolism of polyamines;Metabolism of amino acids and derivatives;Metabolism;Glycine, serine, alanine and threonine metabolism;Creatine metabolism (Consensus)

Recessive Scores

• pRec: 0.0930

Intolerance Scores

• loftool: 0.241
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.469
• hipred: Y
• hipred_score: 0.768
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.222

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc6a8
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype

Gene ontology

• Biological process: creatine metabolic process;sodium ion transport;muscle contraction;choline transport;creatine transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane
• Molecular function: molecular_function;creatine transmembrane transporter activity;creatine:sodium symporter activity;neurotransmitter:sodium symporter activity;choline transmembrane transporter activity