NHERF1 (Na+/H+ Exchanger Regulatory Factor 1)
A scaffold protein regulating ion transport and cell signaling
Gene Information Card
| Symbol | NHERF1 |
|---|---|
| Full Name | Na+/H+ Exchanger Regulatory Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.1 |
| NCBI Gene ID | 9368 ncbi.nlm.nih.gov/gene/9368 |
| Ensembl ID | ENSG00000109062 |
| UniProt ID | O14745 |
| OMIM ID | 604555 |
| HGNC ID | 11075 |
| Aliases | SLC9A3R1, EBP50, NHERF |
Description
NHERF1 (SLC9A3R1) encodes a scaffold protein that links plasma membrane proteins and regulatory components. It contains two PDZ domains and a C-terminal ezrin-binding domain, mediating interactions with ion transporters, receptors, and cytoskeletal elements. NHERF1 regulates renal phosphate reabsorption, acid-base balance, and cell signaling pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cystic fibrosis | NHERF1 modulates CFTR trafficking and function; altered expression affects chloride transport | ClinVar, PMID: 12058026 |
| Nephrolithiasis | Defective NHERF1 impairs renal phosphate handling, contributing to stone formation | OMIM, PMID: 20041220 |
| Breast cancer | NHERF1 overexpression correlates with poor prognosis; regulates PTEN and EGFR signaling | COSMIC, PMID: 23431147 |
| Hypertension | NHERF1 influences sodium-hydrogen exchanger activity in kidney | NCBI Gene, PMID: 10551897 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 45.2 | High |
| Lung | 28.7 | Medium |
| Liver | 12.3 | Low |
| Breast | 18.9 | Medium |
| Colon | 22.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 35.6 | High expression |
| MCF7 | 20.4 | Moderate expression |
| A549 | 15.8 | Low expression |
| Caco-2 | 28.3 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.473C>T (p.Pro158Leu) | Missense | 0.02% (gnomAD) | Alters PDZ2 domain; reduced CFTR binding |
| c.826G>A (p.Glu276Lys) | Missense | 0.01% (gnomAD) | Impairs ezrin binding; disrupted signaling |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Mutations disrupting PDZ domains or ezrin binding reduce scaffold function, impairing ion transporter regulation.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may enhance oncogenic signaling.
Dominant Negative (DN)
Truncated or mislocalized NHERF1 can interfere with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
| • PDZ domain binding | • protein domain specific binding |
| • scaffold protein binding | • ion transmembrane transporter activity |
| • cell-cell junction | • apical plasma membrane |
Pathways
• Regulation of CFTR trafficking
• Renal phosphate reabsorption
• EGFR signaling pathway
• PTEN regulation
Protein Summary
NHERF1 is a 358-amino acid scaffold protein with two PDZ domains and a C-terminal ezrin-binding region. It localizes to the apical membrane of epithelial cells, where it organizes signaling complexes and regulates ion transporters such as NHE3, CFTR, and NaPi-IIa. Through interactions with PTEN and EGFR, NHERF1 also modulates cell growth and survival pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NHERF1 Knockout HEK293 Cell Line | EDJ-KQ3929 | Human | 9368 | Details Get a Quote |
| NHERF1 Knockout A-549 Cell Line | EDJ-KQ26166 | Human | 9368 | Details Get a Quote |
| NHERF1 Knockout HCT 116 Cell Line | EDJ-KQ26167 | Human | 9368 | Details Get a Quote |
| NHERF1 Knockout HeLa Cell Line | EDJ-KQ26168 | Human | 9368 | Details Get a Quote |
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