SLC26A4 (Pendrin) Gene: Structure, Function, and Associated Diseases
A comprehensive overview of the SLC26A4 gene, encoding the pendrin anion exchanger, its role in iodide transport, and its clinical significance in Pendred syndrome and non-syndromic hearing loss.
Gene Information Card
| Symbol | SLC26A4 |
|---|---|
| Full Name | Solute carrier family 26 member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.3 (GRCh38: 7:107,660,828-107,717,809) |
| NCBI Gene ID | 5172 ncbi.nlm.nih.gov/gene/5172 |
| Ensembl ID | ENSG00000091137 |
| UniProt ID | O43511 |
| OMIM ID | 605646 |
| HGNC ID | 11018 |
| Aliases | PDS, DFNB4, Pendrin |
Description
The SLC26A4 gene encodes pendrin, a transmembrane protein belonging to the solute carrier 26 family. Pendrin functions as an anion exchanger, transporting chloride, iodide, bicarbonate, and thiocyanate across cell membranes. It is highly expressed in the inner ear, thyroid, and kidney, playing critical roles in endolymphatic fluid homeostasis, iodide transport, and acid-base balance. Mutations in SLC26A4 are associated with Pendred syndrome (characterized by sensorineural hearing loss, goiter, and enlarged vestibular aqueduct) and non-syndromic hearing loss (DFNB4).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pendred syndrome | Biallelic loss-of-function mutations impair pendrin-mediated iodide transport and endolymphatic ion homeostasis, leading to defective thyroid hormone synthesis and inner ear malformations. | OMIM 274600; ClinVar; multiple publications |
| Non-syndromic hearing loss (DFNB4) | Biallelic mutations cause isolated sensorineural hearing loss with enlarged vestibular aqueduct, without thyroid involvement, due to disrupted endolymphatic pH and ion balance. | OMIM 600791; ClinVar |
| Enlarged vestibular aqueduct (EVA) | Mutations in SLC26A4 are a major cause of EVA, often with or without goiter, affecting inner ear fluid regulation. | ClinVar; literature |
| Goiter (euthyroid) | Pendrin dysfunction leads to defective iodide organification, causing goiter, often with normal thyroid hormone levels. | OMIM; clinical studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid | High (nTPM ~ 50) | Strong expression in thyrocytes, apical membrane |
| Kidney | Moderate (nTPM ~ 20) | Distal nephron, intercalated cells |
| Inner ear (cochlea) | High (nTPM not available) | Endolymphatic sac, vestibular dark cells |
| Lung | Low (nTPM ~ 5) | Minimal expression |
| Testis | Low (nTPM ~ 3) | Weak expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Thyroid epithelial cells | High | Pendrin localized to apical membrane |
| Renal collecting duct cells | Moderate | Type B intercalated cells |
| HeLa | Low | Not endogenously expressed |
| HEK293 | Low | Used for transfection studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.707T>C (p.Leu236Pro) | Missense | Common in Caucasian populations | Loss of function; impaired protein trafficking |
| c.1001+1G>A | Splice site | Reported in multiple ethnicities | Aberrant splicing, loss of function |
| c.1246A>C (p.Thr416Pro) | Missense | Found in Asian populations | Loss of function; reduced anion exchange |
| c.2168A>G (p.His723Arg) | Missense | Reported in Pendred syndrome | Loss of function; protein instability |
| c.1334T>C (p.Leu445Pro) | Missense | Found in DFNB4 | Loss of function; impaired membrane localization |
Mutation functional classification
Loss of Function (LOF)
Most SLC26A4 mutations are loss-of-function, leading to reduced or absent anion exchange activity, often due to protein misfolding, impaired trafficking, or catalytic defects.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SLC26A4.
Dominant Negative (DN)
No dominant-negative effects have been described; the disease is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Anion:chloride antiporter activity | • Bicarbonate transmembrane transporter activity |
| • Iodide transmembrane transporter activity | • Chloride transmembrane transporter activity |
| • Plasma membrane | • Apical plasma membrane |
| • Response to drug | • Ion transport |
| • Chloride transport | • Bicarbonate transport |
Pathways
• Iodide metabolism
• Thyroid hormone synthesis
• Bicarbonate transport in renal collecting duct
• Endolymphatic ion homeostasis
Protein Summary
Pendrin is a 780-amino-acid glycoprotein with 12 transmembrane domains. It functions as an electroneutral exchanger of chloride, iodide, bicarbonate, and thiocyanate. In the thyroid, it mediates iodide efflux at the apical membrane, essential for hormone synthesis. In the inner ear, it regulates endolymph pH and ion composition. In the kidney, it participates in acid-base balance by exchanging chloride for bicarbonate in intercalated cells. Mutations disrupt these processes, leading to clinical phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC26A4 Knockout HEK293 Cell Line | EDJ-KQ2080 | Human | 5172 | Details Get a Quote |
| SLC26A4 Knockout HeLa Cell Line | EDJ-KQ54113 | Human | 5172 | Details Get a Quote |
| SLC26A4 Knockout A-549 Cell Line | EDJ-KQ62601 | Human | 5172 | Details Get a Quote |
| SLC26A4 Knockout HCT 116 Cell Line | EDJ-KQ71074 | Human | 5172 | Details Get a Quote |
| SLC26A4 (p.L676Q) Point Mutation in HCT 116 Cell Line | EDC03102 | Human | 5172 | Details Get a Quote |
| SLC26A4 (p.G197R) Point Mutation in HCT 116 Cell Line | EDC03125 | Human | 5172 | Details Get a Quote |
| SLC26A4 (p.T410M) Point Mutation in HCT 116 Cell Line | EDC03106 | Human | 5172 | Details Get a Quote |
| SLC26A4 (p.H723R) Point Mutation in HCT 116 Cell Line | EDC03107 | Human | 5172 | Details Get a Quote |
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