SLC38A1
protein-codingsolute carrier family 38 member 1, the group of Solute carrier family 38
Gene summary
Amino acid transporters play essential roles in the uptake of nutrients, production of energy, chemical metabolism, detoxification, and neurotransmitter cycling. SLC38A1 is an important transporter of glutamine, an intermediate in the detoxification of ammonia and the production of urea. Glutamine serves as a precursor for the synaptic transmitter, glutamate (Gu et al., 2001 [PubMed 11325958]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~87.0 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 SLC38A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030674.4. 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 | 1 | 2 | |||
| missense | 41 | 41 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 45 | 0 | 1 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_109599.3 | 15 | MANE Select | |
| Ensembl | ENSP00000381634.4 | 15 | MANE Select | |
| RefSeq | NP_001070952.1 | 15 | Standard | |
| RefSeq | NP_001265316.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GABAergic synapse - Homo sapiens (human)
- Glutamatergic synapse - Homo sapiens (human)
- Astrocytic Glutamate-Glutamine Uptake And Metabolism
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
Biological Process
- neurotransmitter uptake
- amino acid transmembrane transport
- sodium ion transport
- amino acid transport
- neutral amino acid transport
Molecular Function
- amino acid:sodium symporter activity
- protein binding
- amino acid transmembrane transporter activity
- neutral amino acid transmembrane transporter activity
- L-amino acid transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398637
- Coding exons
- 15
- Length
- 86955
- Individuals with no LoFs
- 124754
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124760
- p
- 0.0000240
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.15 | 168 | 267 | 0.630 | 0.0000139 | 3188 |
| Missense (PolyPhen) | 42 | 102.48 | 0.40983 | 1285 | ||
| Synonymous | 0.365 | 96 | 101 | 0.954 | 0.00000584 | 921 |
| Loss of Function | 4.01 | 4 | 26.1 | 0.153 | 0.00000128 | 338 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| 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) | 0.000045 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a sodium-dependent amino acid transporter. Mediates the saturable, pH-sensitive and electrogenic cotransport of glutamine and sodium ions with a stoichiometry of 1:1. May also transport small zwitterionic and aliphatic amino acids with a lower affinity. May supply glutamatergic and GABAergic neurons with glutamine which is required for the synthesis of the neurotransmitters glutamate and GABA. {ECO:0000269|PubMed:10891391}.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.175
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.523
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |