SLC36A4
protein-codingsolute carrier family 36 member 4, the group of Solute carrier family 36
Gene summary
SLC36A4 belongs to the SLC36 family of amino acid transporters based on sequence similarity with other family members (e.g., SLC36A1; MIM 606561). SLC36 proteins contain about 500 amino acids and have 9 to 11 transmembrane domains. Unlike other SLC36 family members, which are proton-coupled amino acid transporters, SLC36A4 is a high-affinity/low-capacity non-proton-coupled amino acid transporter (Pillai and Meredith, 2011 [PubMed 21097500]).[supplied by OMIM, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.8 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 SLC36A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152313.4. 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 | ||||
| missense | 73 | 4 | 77 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 79 | 4 | 0 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689526.2 | 11 | MANE Select | |
| Ensembl | ENSP00000317382.4 | 11 | MANE Select | |
| RefSeq | NP_001273068.1 | 7 | Standard | |
| Ensembl | ENSP00000434879.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tryptophan catabolism
- Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism
- Metabolism of amino acids and derivatives
- Metabolism
- Amino acid transport across the plasma membrane
Biological Process
- amino acid transmembrane transport
- L-alanine transport
- proline transport
- tryptophan transport
- L-proline import across plasma membrane
Molecular Function
- amino acid transmembrane transporter activity
- L-alanine transmembrane transporter activity
- L-proline transmembrane transporter activity
- L-tryptophan transmembrane transporter activity
- symporter activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326402
- Coding exons
- 11
- Length
- 53790
- Individuals with no LoFs
- 125628
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 111
- Defined
- 125739
- p
- 0.000441
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0410 | 261 | 259 | 1.01 | 0.0000124 | 3281 |
| Missense (PolyPhen) | 73 | 73.158 | 0.99785 | 971 | ||
| Synonymous | 0.502 | 83 | 89.0 | 0.932 | 0.00000420 | 962 |
| Loss of Function | -0.574 | 24 | 21.2 | 1.13 | 9.78e-7 | 292 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00017 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.0022 | 0.0022 | notable |
| European (Non-Finnish) | 0.00034 | 0.00033 | rare |
| South Asian | 0.00044 | 0.00042 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a sodium-independent electroneutral transporter for tryptophan, proline and alanine. Inhibited by sarcosine. {ECO:0000269|PubMed:21097500}.;
Intolerance Scores
- LoFtool
- 0.932
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.479
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |