SLC14A1 Gene (UT-B Urea Transporter): Function, Expression, and Clinical Significance
A comprehensive biomedical overview of the SLC14A1 gene, encoding the Kidd blood group antigen and urea transporter UT-B, with relevance to erythrocyte function, renal physiology, and disease.
Gene Information Card
| Symbol | SLC14A1 |
|---|---|
| Full Name | Solute carrier family 14 member 1 (urea transporter B) |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.3 (GRCh38: 18:45,661,000-45,690,000) |
| NCBI Gene ID | 6563 ncbi.nlm.nih.gov/gene/6563 |
| Ensembl ID | ENSG00000141469 |
| UniProt ID | Q13336 |
| OMIM ID | 613868 |
| HGNC ID | 10917 |
| Aliases | UT-B, HUT11, JK, RACH1, HsT11879 |
Description
The SLC14A1 gene encodes the urea transporter B (UT-B), a membrane protein that facilitates the rapid, passive transport of urea across cell membranes. UT-B is highly expressed in erythrocytes (where it constitutes the Kidd blood group antigen) and in the descending vasa recta of the renal medulla, playing a critical role in urinary concentration and urea recycling. The gene spans approximately 29 kb on chromosome 18q12.3 and contains 11 exons. Alternative splicing generates multiple transcript variants, but the main protein is a 389-amino acid glycoprotein with 10 transmembrane domains. UT-B functions as a urea channel, and its absence (due to null mutations) results in the Jk(a-b-) blood group phenotype, which is associated with reduced urine concentrating ability and resistance to certain hemolytic conditions. SLC14A1 is also implicated in susceptibility to bladder cancer and other conditions, though the mechanisms are under investigation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Kidd blood group null phenotype (Jk(a-b-)) | Loss-of-function mutations in SLC14A1 lead to absence of UT-B protein on erythrocytes, resulting in the Jk(a-b-) phenotype. This is associated with impaired urea transport in erythrocytes and renal medulla, leading to reduced urine concentrating ability. | ClinVar; OMIM (613868); multiple case reports |
| Hemolytic transfusion reaction | Individuals with Jk(a-b-) phenotype can develop anti-Jk3 antibodies upon exposure to Kidd antigens, causing delayed hemolytic transfusion reactions. The mechanism involves antibody-mediated destruction of transfused red blood cells. | ClinVar; literature (e.g., transfusion medicine reviews) |
| Bladder cancer susceptibility | Polymorphisms in SLC14A1 (e.g., rs1058396) have been associated with altered risk of bladder cancer. The mechanism may involve changes in urea concentration in urine affecting urothelial cell exposure to carcinogens, though exact pathways are not fully defined. | COSMIC; GWAS studies (e.g., Garcia-Closas et al., 2011) |
| Renal concentrating defect | UT-B deficiency in renal medulla impairs urea recycling, leading to reduced maximal urine osmolality and polyuria under water deprivation. This is a physiological consequence of SLC14A1 loss-of-function. | Mouse models and human studies (e.g., Sands et al., 2000) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Erythrocytes | Not applicable (nTPM not defined for blood cells) | Very high (protein level) |
| Kidney (medulla) | Not available (GTEx nTPM not specific for medulla) | High |
| Bone Marrow | ~10.2 | Medium |
| Lung | ~5.3 | Low |
| Liver | ~2.1 | Low |
| Testis | ~1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (erythroleukemia) | Not available | High expression of UT-B mRNA and protein |
| HEK293 (embryonic kidney) | Not available | Moderate expression; used for functional studies |
| HUVEC (endothelial) | Not available | Low expression |
| HeLa (cervical cancer) | Not available | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.871C>T (p.Arg291Ter) | Nonsense | Rare (found in Jk(a-b-) individuals) | Premature stop codon; loss of UT-B protein function |
| c.956C>T (p.Pro319Leu) | Missense | Rare (found in Jk(a-b-) individuals) | Disrupts urea transport activity |
| c.1125G>A (p.Trp375Ter) | Nonsense | Rare (found in Jk(a-b-) individuals) | Truncated protein; loss of function |
| rs1058396 (intronic variant) | SNP | Common (minor allele frequency ~0.2) | Associated with bladder cancer risk; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that abolish urea transport activity, leading to Jk(a-b-) phenotype and renal concentrating defect.
Gain of Function (GOF)
No gain-of-function mutations reported for SLC14A1.
Dominant Negative (DN)
No dominant-negative effects described; SLC14A1 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • Urea transmembrane transporter activity (GO:0015204) | • Urea channel activity (GO:0015265) |
| • Plasma membrane (GO:0005886) | • Integral component of plasma membrane (GO:0005887) |
| • Urea transport (GO:0015840) | • Response to urea (GO:0043456) |
Pathways
• Urea transport and renal water homeostasis (Reactome: R-HSA-425366)
• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)
Protein Summary
The UT-B protein (UniProt Q13336) is a 389-amino acid, 10-transmembrane-domain glycoprotein that forms a urea-selective channel. It exists as a homotrimer in the plasma membrane and facilitates rapid urea flux down its concentration gradient. In erythrocytes, UT-B carries the Kidd blood group antigens (Jka and Jkb), which are defined by a single amino acid polymorphism (Asp280Asn). UT-B is also expressed in the basolateral membrane of renal medullary vasa recta endothelial cells, where it participates in the countercurrent exchange of urea, crucial for urine concentration. The protein is N-glycosylated at Asn211, which is essential for its function. UT-B knockout mice exhibit polyuria and reduced urine osmolality, confirming its role in renal water conservation. In humans, loss of UT-B is not lethal but leads to the Jk(a-b-) phenotype, which is associated with a mild urinary concentrating defect and potential transfusion complications.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC14A1 Knockout HEK293 Cell Line | EDJ-KQ5790 | Human | 6563 | Details Get a Quote |
| SLC14A1 Knockout HeLa Cell Line | EDJ-KQ54509 | Human | 6563 | Details Get a Quote |
| SLC14A1 Knockout A-549 Cell Line | EDJ-KQ62994 | Human | 6563 | Details Get a Quote |
| SLC14A1 Knockout HCT 116 Cell Line | EDJ-KQ71465 | Human | 6563 | Details Get a Quote |
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