SLC6A6
protein-codingsolute carrier family 6 member 6, the group of Solute carrier family 6
Gene summary
This gene encodes a multi-pass membrane protein that is a member of a family of sodium and chloride-ion dependent transporters. The encoded protein transports taurine and beta-alanine. There is a pseudogene for this gene on chromosome 21. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0007777
Submitter: ClinGen
*SLC6A6* was first reported in relation to autosomal recessive hypotaurinemic retinal degeneration and cardiomyopathy in 2019 by Preising MN et al. (PMID:31345061). In total, two probands with two homozygous variants have been identified. All probands demonstrated progressive retinal degeneration accompanied by progressive visual impairment and/or loss. Two sibilings from Ansar M et al. (PMID:31903486), presented with cardiomyopathy in addition to retinal degeneration. Cardiomyopathy was reversed and retinal degeneration was halted upon oral taurine supplementation in the proband. Evidence supporting this gene-disease relationship includes case-level data and experimental data including biochemical function, a mouse model, and functional alteration. *SLC6A6* or TauT is a sodium and chloride dependent transporter with preference for amino acids such as taurine and alanine. TauT likely functions to transport taurine across the inner blood retina barrier and regulates taurine levels within the retina (PMID:17137607). Knock out *SLC6A6* mice recapitulated the phenotype of significant and progressive retinal degeneration observed in humans (PMID:11772953). Finally, several missense variants transfected into TauT expressing oocytes showed significant and varying degrees of taurine uptake impairment (PMID:24790004). A classification of limited was reached on 3/10/2023 by the Aminoacidopathy GCEP (SOP version 9).
Inheritance Pattern: AR
Disease ID:MONDO:0007777
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Cardiovascular; Ophthalmologic
Intervention: Biochemical; Cardiovascular
Rationale: Oral taurine supplementation has been described as being beneficial; Individuals have been described with cardiomyopathy, and awareness may allow early diagnosis and management of cardiac sequelae
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC6A6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003043.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 4 | 1 | 8 | ||
| missense | 1 | 2 | 67 | 3 | 1 | 74 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 2 | 74 | 7 | 2 | 86 |
Highest pathogenic variant AF is 6.885535e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003034.2 | 13 | MANE Select | |
| Ensembl | ENSP00000480890.1 | 13 | MANE Select | |
| RefSeq | NP_001127839.2 | 15 | Standard | |
| RefSeq | NP_001127840.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| slc6a6b | Danio rerio | Structure: whole organism Quality: lethal (sensu genetics) abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- Amine compound SLC transporters
- Amino acid transport across the plasma membrane
- Amino acid and oligopeptide SLC transporters
Biological Process
- amino acid transmembrane transport
- cellular amino acid metabolic process
- neurotransmitter transport
- amino acid transport
- taurine transport
Molecular Function
- neurotransmitter:sodium symporter activity
- taurine:sodium symporter activity
- amino acid transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000454876
- Coding exons
- 13
- Length
- 86782
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125748
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.39 | 191 | 376 | 0.508 | 0.0000219 | 4045 |
| Missense (PolyPhen) | 55 | 181.42 | 0.30317 | 2047 | ||
| Synonymous | 0.263 | 155 | 159 | 0.973 | 0.0000107 | 1230 |
| Loss of Function | 4.53 | 4 | 31.4 | 0.127 | 0.00000143 | 352 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sodium-dependent taurine and beta-alanine transporter. Chloride ions are necessary for optimal uptake. {ECO:0000269|PubMed:8382624}.;
Intolerance Scores
- LoFtool
- 0.301
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.266
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |