SLC38A4
protein-codingsolute carrier family 38 member 4, the group of Solute carrier family 38
Gene summary
SLC38A4 is found predominantly in liver and transports both cationic and neutral amino acids. The transport of cationic amino acids by SLC38A4 is Na(+) and pH independent, while the transport of neutral amino acids is Na(+) and pH dependent (Hatanaka et al., 2001 [PubMed 11342143]).[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 ~67.6 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 SLC38A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018018.5. 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 | ||||
| missense | 49 | 2 | 51 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 50 | 2 | 1 | 53 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060488.2 | 15 | MANE Select | |
| Ensembl | ENSP00000266579.4 | 15 | MANE Select | |
| RefSeq | NP_001137296.1 | 15 | Standard | |
| Ensembl | ENSP00000389843.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Polythiazide Action Pathway
- Methyclothiazide Action Pathway
- Bumetanide Action Pathway
- Spironolactone Action Pathway
- Eplerenone Action Pathway
Biological Process
- amino acid transmembrane transport
- sodium ion transport
- amino acid transport
Molecular Function
- amino acid transmembrane transporter activity
- symporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000447411
- Coding exons
- 15
- Length
- 67646
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125667
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 225 | 298 | 0.755 | 0.0000147 | 3588 |
| Missense (PolyPhen) | 64 | 114.09 | 0.56098 | 1368 | ||
| Synonymous | 0.758 | 93 | 103 | 0.905 | 0.00000513 | 1041 |
| Loss of Function | 3.92 | 6 | 28.7 | 0.209 | 0.00000150 | 355 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sodium-dependent amino acid transporter. Mediates electrogenic symport of neutral amino acids and sodium ions. Has a broad specificity, with a preference for Ala, followed by His, Cys, Asn, Ser, Gly, Val, Thr, Gln and Met. May mediate sodium- independent transport of cationic amino acids, such as Arg and Lys. Amino acid uptake is pH-dependent, with low transport activities at pH 6.5, intermediate at pH 7.0 and highest between pH 7.5 and 8.5. {ECO:0000269|PubMed:11342143, ECO:0000269|PubMed:11414754}.;
Recessive Scores
- pRec
- 0.164
Intolerance Scores
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.230
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |