NPHP3: Nephrocystin-3 and Its Role in Ciliopathies
Comprehensive gene card for NPHP3, associated with nephronophthisis and related renal ciliopathies
Gene Information Card
| Symbol | NPHP3 |
|---|---|
| Full Name | nephrocystin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q22.1 |
| NCBI Gene ID | 27031 ncbi.nlm.nih.gov/gene/27031 |
| Ensembl ID | ENSG00000113916 |
| UniProt ID | Q7Z494 |
| OMIM ID | 608002 |
| HGNC ID | 7907 |
| Aliases | NPH3, MKS7, SLSN3, nephrocystin-3 |
Description
NPHP3 encodes nephrocystin-3, a protein involved in primary cilia function and planar cell polarity. Mutations in NPHP3 cause nephronophthisis type 3 (NPHP3), an autosomal recessive kidney disease characterized by tubular basement membrane disruption and cyst formation, and can also lead to Meckel-Gruber syndrome type 7 (MKS7) and Senior-Løken syndrome type 3 (SLSN3). The protein interacts with other nephrocystins and is essential for ciliary signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nephronophthisis 3 (NPHP3) | Loss-of-function mutations disrupt ciliary function, leading to renal tubular degeneration and fibrosis. | OMIM #604387; ClinVar |
| Meckel-Gruber syndrome 7 (MKS7) | Biallelic NPHP3 mutations cause severe ciliopathy with renal cysts, encephalocele, and polydactyly. | OMIM #608002; ClinVar |
| Senior-Løken syndrome 3 (SLSN3) | NPHP3 mutations combined with retinal degeneration result in nephronophthisis and retinitis pigmentosa. | OMIM #610189; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Testis | 8.3 | Medium |
| Brain | 6.1 | Low |
| Liver | 4.2 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney cells |
| HepG2 | 7.4 | Liver cancer cells |
| A549 | 5.1 | Lung cancer cells |
| K562 | 2.3 | Leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2146C>T (p.Arg716*) | Nonsense | Rare | Premature stop, loss of function |
| c.1090C>T (p.Arg364Trp) | Missense | Rare | Impaired protein stability |
| c.1414delA (p.Thr472Profs*13) | Frameshift | Rare | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most NPHP3 mutations are loss-of-function, leading to truncated or unstable protein, disrupting ciliary function.
Gain of Function (GOF)
No gain-of-function mutations reported for NPHP3.
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 projection organization (GO:0030030) | • cilium assembly (GO:0060271) |
| • cytoplasm (GO:0005737) |
Pathways
• Ciliopathy pathway (Reactome: R-HSA-5620920)
• Hedgehog signaling (involved in ciliary signaling)
Protein Summary
Nephrocystin-3 is a 1330-amino acid protein containing a coiled-coil domain and a tubulin-tyrosine ligase (TTL) domain. It localizes to primary cilia and centrosomes, interacting with NPHP1, NPHP4, and inversin to regulate ciliary signaling and planar cell polarity. Defects in NPHP3 cause ciliary dysfunction leading to renal cystic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPHP3 Knockout HEK293 Cell Line | EDJ-KQ8648 | Human | 27031 | Details Get a Quote |
| NPHP3 Knockout HCT 116 Cell Line | EDJ-KQ33542 | Human | 27031 | Details Get a Quote |
| NPHP3 Knockout A-549 Cell Line | EDJ-KQ34819 | Human | 27031 | Details Get a Quote |
| NPHP3 Knockout HeLa Cell Line | EDJ-KQ34820 | Human | 27031 | Details Get a Quote |
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