SLC22A4 (OCTN1): Solute Carrier Family 22 Member 4
A key transporter in carnitine homeostasis, inflammatory bowel disease susceptibility, and drug disposition.
Gene Information Card
| Symbol | SLC22A4 |
|---|---|
| Full Name | Solute carrier family 22 member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 6583 ncbi.nlm.nih.gov/gene/6583 |
| Ensembl ID | ENSG00000197299 |
| UniProt ID | Q9H015 |
| OMIM ID | 604190 |
| HGNC ID | 10968 |
| Aliases | OCTN1, MGC3453, FLJ22348 |
Description
SLC22A4 encodes the organic cation/carnitine transporter 1 (OCTN1), a plasma membrane protein that mediates the transport of organic cations, zwitterions, and carnitine. It is expressed in various tissues including the intestine, kidney, and immune cells. Genetic variants in SLC22A4 have been associated with susceptibility to inflammatory bowel disease (Crohn's disease) and rheumatoid arthritis. The protein plays a role in carnitine homeostasis and may influence drug disposition and inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Crohn's disease | The SLC22A4 1672C>T (L503F) variant is associated with altered transporter function, potentially affecting carnitine uptake and inflammatory responses in the gut. | Association studies (e.g., Peltekova et al., 2004; OMIM 604190) |
| Rheumatoid arthritis | The same SLC22A4 variant (L503F) has been linked to increased susceptibility, possibly through effects on carnitine transport in immune cells. | Genetic association studies (e.g., Tokuhiro et al., 2003; OMIM 604190) |
| Carnitine deficiency (secondary) | Loss-of-function mutations may impair carnitine transport, contributing to systemic carnitine deficiency, though primary defects are rare. | Case reports and functional studies (UniProt Q9H015) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High | nTPM ~ 50-100 (based on GTEx) |
| Small intestine | High | nTPM ~ 40-80 |
| Colon | Moderate | nTPM ~ 20-40 |
| Liver | Low | nTPM ~ 5-10 |
| Brain | Low | nTPM ~ 1-5 |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | Moderate | Intestinal epithelial cell line |
| HepG2 | Low | Hepatocellular carcinoma cell line |
| HEK293 | Low | Embryonic kidney cells (often used for transfection) |
| THP-1 | Moderate | Monocytic leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| L503F (1672C>T) | Missense | ~30-40% in European populations | Altered transport activity; associated with Crohn's disease and rheumatoid arthritis |
| R399C | Missense | Rare | Reduced carnitine transport in vitro |
| M205V | Missense | Rare | Potential effect on substrate specificity |
Mutation functional classification
Loss of Function (LOF)
R399C and other rare missense variants reduce carnitine transport activity, leading to impaired cellular uptake.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; L503F may alter substrate affinity but not necessarily increase activity.
Dominant Negative (DN)
Not established; SLC22A4 functions as a monomer, and dominant-negative effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005215 - transporter activity | • GO:0008028 - monocarboxylic acid transmembrane transporter activity |
| • GO:0015293 - symporter activity | • GO:0016020 - membrane |
| • GO:0005886 - plasma membrane | • GO:0015879 - carnitine transport |
| • GO:0055085 - transmembrane transport |
Pathways
• Carnitine shuttle (Reactome: R-HSA-897886)
• Transport of organic cations (Reactome: R-HSA-425393)
Protein Summary
OCTN1 is a 551-amino acid protein with 11 transmembrane domains. It functions as a sodium-dependent carnitine transporter and also transports organic cations such as tetraethylammonium. It is involved in cellular carnitine homeostasis, which is essential for fatty acid oxidation. The protein is localized to the plasma membrane and is expressed in absorptive and immune cells. Its activity can be modulated by genetic variants, impacting disease susceptibility and drug pharmacokinetics.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC22A4 Knockout HEK293 Cell Line | EDJ-KQ5800 | Human | 6583 | Details Get a Quote |
| SLC22A4 Knockout A-549 Cell Line | EDJ-KQ29212 | Human | 6583 | Details Get a Quote |
| SLC22A4 Knockout HCT 116 Cell Line | EDJ-KQ29213 | Human | 6583 | Details Get a Quote |
| SLC22A4 Knockout HeLa Cell Line | EDJ-KQ29214 | Human | 6583 | Details Get a Quote |
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