NPHP1 Gene - Nephrocystin-1
Key Gene in Nephronophthisis and Ciliopathies
Gene Information Card
| Symbol | NPHP1 |
|---|---|
| Full Name | Nephrocystin-1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q13 |
| NCBI Gene ID | 4867 ncbi.nlm.nih.gov/gene/4867 |
| Ensembl ID | ENSG00000144061 |
| UniProt ID | O15259 |
| OMIM ID | 607100 |
| HGNC ID | 7905 |
| Aliases | JBTS4, SLSN1, NPH1 |
Description
NPHP1 encodes nephrocystin-1, a protein involved in ciliary function and cell-cell adhesion. Mutations in NPHP1 are the most common cause of nephronophthisis, an autosomal recessive cystic kidney disease, and are also associated with Joubert syndrome and Senior-Løken syndrome. The protein localizes to primary cilia, centrosomes, and adherens junctions, playing a role in signaling pathways such as Wnt and Hedgehog.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nephronophthisis 1 (NPH1) | Loss of function leads to disrupted ciliary signaling and renal tubular degeneration | OMIM #256100; ClinVar |
| Joubert Syndrome 4 (JBTS4) | Defective ciliary function causes cerebellar and retinal abnormalities | OMIM #609583; ClinVar |
| Senior-Løken Syndrome 1 (SLSN1) | Combined renal and retinal degeneration due to ciliary dysfunction | OMIM #266900; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Testis | 8.3 | Medium |
| Brain | 5.1 | Low |
| Liver | 2.0 | Low |
| Heart | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| HeLa | 6.7 | Moderate expression |
| HepG2 | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.168_169del (p.Glu57fs) | Frameshift | ~20% in NPH1 | Loss of function |
| c.442C>T (p.Arg148*) | Nonsense | ~5% | Premature truncation |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein production |
Mutation functional classification
Loss of Function (LOF)
Most NPHP1 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to truncated or absent nephrocystin-1 and disrupted ciliary function.
Gain of Function (GOF)
No gain-of-function mutations reported for NPHP1.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • cilium (GO:0005929) |
| • cell-cell junction (GO:0005911) | • signal transduction (GO:0007165) |
| • cell projection organization (GO:0030030) |
Pathways
• Ciliopathy pathway (KEGG: hsa05200)
• Wnt signaling pathway (Reactome: R-HSA-195721)
Protein Summary
Nephrocystin-1 is a 732-amino acid protein containing an SH3 domain and multiple coiled-coil regions. It interacts with other nephrocystins (NPHP2-8) and proteins such as inversin and β-tubulin, forming a complex essential for primary cilium integrity and function. Defects in this protein lead to progressive renal fibrosis and extrarenal manifestations.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPHP1 Knockout HEK293 Cell Line | EDJ-KQ14462 | Human | 4867 | Details Get a Quote |
| NPHP1 Knockout A-549 Cell Line | EDJ-KQ44696 | Human | 4867 | Details Get a Quote |
| NPHP1 Knockout HCT 116 Cell Line | EDJ-KQ44697 | Human | 4867 | Details Get a Quote |
| NPHP1 Knockout HeLa Cell Line | EDJ-KQ44698 | Human | 4867 | Details Get a Quote |
| NPHP1 Knockout MDCK Cell Line | EDJ-KZ370 | Dog | 403780 | Details Get a Quote |
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