SLC18A1
protein-codingsolute carrier family 18 member A1, the group of Solute carrier family 18
Gene summary
The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008]
- VMAT1
- VAT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.4 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 SLC18A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003053.4. 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 | 2 | ||||
| missense | 114 | 3 | 117 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 114 | 5 | 0 | 119 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003044.1 | 15 | MANE Select | |
| Ensembl | ENSP00000276373.5 | 15 | MANE Select | |
| RefSeq | NP_001129163.1 | 15 | Standard | |
| RefSeq | NP_001135796.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Synaptic vesicle cycle - Homo sapiens (human)
- Serotonergic synapse - Homo sapiens (human)
- Dopaminergic synapse - Homo sapiens (human)
- Amphetamine addiction - Homo sapiens (human)
- Parkinson,s disease - Homo sapiens (human)
Biological Process
- neurotransmitter transport
- drug transmembrane transport
- aminergic neurotransmitter loading into synaptic vesicle
- monoamine transport
- serotonin uptake
Molecular Function
- serotonin:sodium symporter activity
- monoamine transmembrane transporter activity
- drug transmembrane transporter activity
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
- cell junction
- synaptic vesicle membrane
- terminal bouton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000440926
- Coding exons
- 15
- Length
- 38352
- Individuals with no LoFs
- 125534
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 214
- Defined
- 125748
- p
- 0.000851
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.38 | 420 | 303 | 1.39 | 0.0000161 | 3382 |
| Missense (PolyPhen) | 191 | 128.78 | 1.4832 | 1479 | ||
| Synonymous | -2.08 | 143 | 115 | 1.25 | 0.00000632 | 1079 |
| Loss of Function | -0.783 | 29 | 24.8 | 1.17 | 0.00000124 | 279 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.0036 | 0.0035 | notable |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00094 | 0.00092 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00029 | 0.00029 | rare |
| South Asian | 0.00091 | 0.00088 | rare |
| Other | 0.00084 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the transport of biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles of neuroendocrine and endocrine cells. {ECO:0000269|PubMed:16326835, ECO:0000269|PubMed:8643547}.;
Recessive Scores
- pRec
- 0.205
Intolerance Scores
- LoFtool
- 0.609
- RVIS EVS
- 1.03
- RVIS percentile EVS
- 91.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.634
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |