SLC22A1
protein-codingsolute carrier family 22 member 1, the group of Solute carrier family 22
Gene summary
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.9 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 SLC22A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003057.3. 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 | 4 | 3 | 8 | ||
| missense | 80 | 2 | 2 | 84 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 81 | 6 | 5 | 92 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003048.1 | 11 | MANE Select | |
| Ensembl | ENSP00000355930.4 | 11 | MANE Select | |
| RefSeq | NP_001424264.1 | 9 | Standard | |
| RefSeq | NP_694857.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Choline metabolism in cancer - Homo sapiens (human)
- Bile secretion - Homo sapiens (human)
- Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics
- Tramadol Pharmacokinetics
- Metformin Pathway, Pharmacokinetics
Biological Process
- neurotransmitter transport
- drug transmembrane transport
- establishment or maintenance of transmembrane electrochemical gradient
- organic cation transport
- quaternary ammonium group transport
Molecular Function
- acetylcholine transmembrane transporter activity
- dopamine:sodium symporter activity
- norepinephrine:sodium symporter activity
- protein binding
- secondary active organic cation transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366963
- Coding exons
- 11
- Length
- 36930
- Individuals with no LoFs
- 125549
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 199
- Defined
- 125748
- p
- 0.000792
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0948 | 339 | 334 | 1.01 | 0.0000199 | 3554 |
| Missense (PolyPhen) | 120 | 117.76 | 1.019 | 1331 | ||
| Synonymous | -0.646 | 165 | 155 | 1.07 | 0.0000108 | 1165 |
| Loss of Function | -1.09 | 30 | 24.2 | 1.24 | 0.00000112 | 269 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0013 | 0.0011 | notable |
| Finnish | 0.00015 | 0.00014 | rare |
| European (Non-Finnish) | 0.00090 | 0.00083 | rare |
| South Asian | 0.00050 | 0.00049 | rare |
| Other | 0.0010 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase. {ECO:0000269|PubMed:11388889, ECO:0000269|PubMed:11408531, ECO:0000269|PubMed:15389554, ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093, ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9655880}.;
Recessive Scores
- pRec
- 0.205
Intolerance Scores
- LoFtool
- 0.920
- RVIS EVS
- 1.78
- RVIS percentile EVS
- 96.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.715
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |