SLC29A4
protein-codingsolute carrier family 29 member 4, the group of Solute carrier family 29
Gene summary
This gene encodes a member of the SLC29A/ENT transporter protein family. The encoded membrane protein catalyzes the reuptake of monoamines into presynaptic neurons, thus determining the intensity and duration of monoamine neural signaling. It has been shown to transport several compounds, including serotonin, dopamine, and the neurotoxin 1-methyl-4-phenylpyridinium. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.5 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 SLC29A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153247.4. 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 | 2 | 13 | 4 | 19 | ||
| missense | 132 | 7 | 4 | 143 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 135 | 20 | 8 | 163 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_694979.2 | 10 | MANE Select | |
| Ensembl | ENSP00000380081.2 | 10 | MANE Select | |
| RefSeq | NP_001035751.1 | 10 | Standard | |
| RefSeq | NP_001287776.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metformin Pathway, Pharmacokinetics
- Tyrosine metabolism
- Transport of vitamins, nucleosides, and related molecules
- SLC-mediated transmembrane transport
- Transport of small molecules
Biological Process
- monoamine transport
- nucleoside transmembrane transport
Molecular Function
- nucleoside transmembrane transporter activity
- monoamine transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396872
- Coding exons
- 10
- Length
- 32502
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125743
- p
- 0.000270
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.00 | 420 | 366 | 1.15 | 0.0000250 | 3392 |
| Missense (PolyPhen) | 112 | 114.49 | 0.97825 | 1099 | ||
| Synonymous | -7.15 | 292 | 172 | 1.69 | 0.0000134 | 1130 |
| Loss of Function | 1.82 | 11 | 19.7 | 0.557 | 9.06e-7 | 219 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00032 | 0.00030 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00017 | 0.00014 | rare |
| European (Non-Finnish) | 0.00040 | 0.00039 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00052 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including serotonin, dopamine, norepinephrine and epinephrine. May play a role in regulating central nervous system homeostasis of monoamine neurotransmitters. May be involved in luminal transport of organic cations in the kidney and seems to use luminal proton gradient to drive organic cation reabsorption. Does not seem to transport nucleoside and nucleoside analogs such as uridine, cytidine, thymidine, adenosine, inosine, guanosine, and azidothymidine. In (PubMed:16873718) adenosine is efficiently transported but in a fashion highly sensitive to extracellular pH, with maximal activity in the pH range 5.5 to 6.5. Glu-206 is essential for the cation selectivity and may function as the charge sensor for cationic substrates. Transport is chloride and sodium-independent but appears to be sensitive to changes in membrane potential. Weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine. May play a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia. {ECO:0000269|PubMed:15448143, ECO:0000269|PubMed:16873718, ECO:0000269|PubMed:17018840, ECO:0000269|PubMed:17121826}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.566
- RVIS EVS
- -0.99
- RVIS percentile EVS
- 8.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.254
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |