SLC6A18
protein-codingsolute carrier family 6 member 18, the group of Solute carrier family 6
Gene summary
The SLC6 family of proteins, which includes SLC6A18, act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine. SLC6 proteins are sodium cotransporters that derive the energy for solute transport from the electrochemical gradient for sodium ions (Hoglund et al., 2005 [PubMed 16125675]).[supplied by OMIM, Apr 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC6A18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182632.3. 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 | 1 | 3 | 5 | 9 | ||
| missense | 120 | 18 | 7 | 145 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 122 | 21 | 12 | 155 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_872438.2 | 12 | MANE Select | |
| Ensembl | ENSP00000323549.3 | 12 | MANE Select |
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
- neurotransmitter transport
- amino acid transport
- neutral amino acid transport
Molecular Function
- neurotransmitter:sodium symporter activity
- amino acid transmembrane transporter activity
- neutral amino acid transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- apical plasma membrane
- brush border membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324642
- Coding exons
- 12
- Length
- 20835
- Individuals with no LoFs
- 51499
- Homozygous LoFs
- 16859
- Heterozygous LoFs
- 57390
- Defined
- 125748
- p
- 0.360
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.194 | 395 | 406 | 0.973 | 0.0000262 | 4034 |
| Missense (PolyPhen) | 157 | 149.04 | 1.0534 | 1697 | ||
| Synonymous | 0.526 | 182 | 191 | 0.952 | 0.0000142 | 1293 |
| Loss of Function | -0.425 | 31 | 28.6 | 1.09 | 0.00000142 | 284 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.35 | 0.35 | notable |
| Latino/Admixed American | 0.37 | 0.37 | notable |
| Ashkenazi Jewish | 0.29 | 0.29 | notable |
| East Asian | 0.24 | 0.24 | notable |
| Finnish | 0.33 | 0.33 | notable |
| European (Non-Finnish) | 0.39 | 0.39 | notable |
| South Asian | 0.40 | 0.40 | notable |
| Other | 0.35 | 0.35 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a sodium and chloride-dependent neutral amino acid transporter. {ECO:0000250}.;
- Disease
- DISEASE: Note=Genetic variations in SLC6A18 might contribute to the disease phentotype in some individuals with iminoglycinuria or hyperglycinuria, that carry variants in SLC36A2, SLC6A19 or SLC6A20 (PubMed:19033659). {ECO:0000269|PubMed:19033659}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.847
- RVIS EVS
- 1.01
- RVIS percentile EVS
- 90.81
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.377
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |