SLC6A1
protein-codingsolute carrier family 6 member 1, the group of Solute carrier family 6
Gene summary
The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014633
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0016025
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014633
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014633
Submitter: Illumina
Inheritance Pattern: AD
Disease ID:MONDO:0014633
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014633
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC6A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003042.4. 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 | 7 | 210 | 6 | 224 | |
| missense | 24 | 85 | 311 | 70 | 21 | 511 |
| nonsense | 26 | 7 | 2 | 35 | ||
| start loss | 1 | 1 | ||||
| frameshift | 27 | 10 | 6 | 43 | ||
| splice donor/acceptor (+/-2bp) | 11 | 16 | 2 | 29 | ||
| Total | 89 | 119 | 328 | 280 | 27 | 843 |
Highest pathogenic variant AF is 0.000012396766
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003033.3 | 14 | MANE Select | |
| Ensembl | ENSP00000287766.4 | 14 | MANE Select | |
| RefSeq | NP_001335179.1 | 14 | Standard | |
| RefSeq | NP_001335180.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Benzodiazepine Pathway, Pharmacodynamics
- GABAergic synapse - Homo sapiens (human)
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- Monoamine Transport
Biological Process
- chemical synaptic transmission
- learning
- response to toxic substance
- response to sucrose
- response to lead ion
Molecular Function
- gamma-aminobutyric acid:sodium symporter activity
- protein binding
- neurotransmitter binding
- metal ion binding
Cellular Component
- plasma membrane
- cell surface
- membrane
- integral component of membrane
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000287766
- Coding exons
- 14
- Length
- 46524
- Individuals with no LoFs
- 123129
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123130
- p
- 0.00000406
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.18 | 144 | 370 | 0.389 | 0.0000217 | 3926 |
| Missense (PolyPhen) | 21 | 145.69 | 0.14414 | 1586 | ||
| Synonymous | -0.958 | 170 | 155 | 1.10 | 0.0000102 | 1176 |
| Loss of Function | 5.05 | 1 | 31.7 | 0.0316 | 0.00000144 | 340 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000090 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.;
- Disease
- DISEASE: Myoclonic-atonic epilepsy (MAE) [MIM:616421]: A form of epilepsy characterized by myoclonic-atonic and absence seizures, appearing in early childhood. Patients have delayed development before the onset of seizures and show varying degrees of intellectual disability following seizure onset. {ECO:0000269|PubMed:25865495}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.240
Intolerance Scores
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 29.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.836
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |