# NPHP1 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- Pathogenic variants in *NPHP1* are the primary monogenic cause of nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, and are associated with a spectrum of ciliopathies including Senior-Løken syndrome and Joubert syndrome.
- The most frequent pathogenic variant is a recurrent ~290 kb homozygous deletion of the entire *NPHP1* coding region, detectable by MLPA or CMA, accounting for 40-50% of alleles in European cohorts.
- Nephrocystin-1 functions as a scaffold protein at the ciliary transition zone, regulating Wnt/PCP signaling, actin cytoskeleton dynamics, and cell-cell adhesion through interactions with proteins like DVL and p130Cas.
- Genotype-phenotype correlations indicate that null alleles (deletions, nonsense, frameshift) are associated with severe renal disease and a higher risk of retinal involvement, while missense mutations in specific domains can lead to isolated renal disease or Joubert syndrome.
- Therapeutic strategies under investigation include translational readthrough agents for nonsense mutations, proteostasis modulators to stabilize residual protein, and gene therapy approaches utilizing CRISPR-Cas9 or AAV vectors for the common deletion.

---

## Executive Summary & Key Metadata

The *NPHP1* gene (nephrocystin-1) encodes a highly conserved ciliary protein that operates as a molecular scaffold at the transition zone of primary cilia. Its dysfunction is the principal monogenic cause of nephronophthisis (NPHP), an autosomal recessive cystic kidney disease that progresses to end-stage renal failure (ESRF) in the first three decades of life. Beyond the renal phenotype, pathogenic variants in *NPHP1* produce a pleiotropic spectrum of ciliopathies, including Senior-Løken syndrome (retinal degeneration), Joubert syndrome (cerebellar vermis hypoplasia), and Cogan-type oculomotor apraxia. This reference manual provides a comprehensive, biophysically grounded analysis of the gene's genomic architecture, protein domain organization, signaling integration, mutation spectrum, and emerging therapeutic avenues.

| **Attribute** | **Value** |
|---|---|
| **HGNC Symbol** | NPHP1 |
| **UniProt Accession** | O15259 |
| **Representative PDB ID** | true (AlphaFold model; no high-resolution experimental structure yet) |
| **Chromosomal Locus** | 2q13 (GRCh38: chr2:110,123,348–110,205,208; minus strand) |
| **Primary Molecular Function** | Scaffold protein at ciliary transition zone; regulates actin cytoskeleton, cell-cell adhesion, and Wnt/PCP signaling |
| **Disease & Pathology Associations** | Nephronophthisis 1 (NPHP1), Joubert syndrome 4 (JBTS4), Senior-Løken syndrome 1 (SLSN1), Cogan-type oculomotor apraxia (OMIM #607100) |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Context and Gene Structure

*NPHP1* is located on the long arm of chromosome 2 at band q13, a region notorious for genomic instability due to the presence of large, highly homologous segmental duplications. The gene spans approximately 82 kilobases (kb) of genomic DNA and is transcribed from the minus (Crick) strand. The genomic architecture is defined by 20 canonical exons, of which the first exon is non-coding and contains the core promoter elements. The coding sequence begins in exon 2 and terminates in exon 20, producing a mature mRNA of approximately 4.5 kb.

The 2q13 locus is flanked by two large (~350 kb) low-copy repeats (LCRs) designated LCR-A and LCR-B. These LCRs share >99% sequence identity and mediate non-allelic homologous recombination (NAHR) during meiosis. This recombination event generates a recurrent ~290 kb homozygous deletion that removes the entire *NPHP1* coding region. This deletion accounts for approximately 40–50% of all NPHP1 alleles in European cohorts, making it one of the most frequent structural variants associated with a recessive Mendelian disorder. The deletion breakpoints cluster within a 12 kb region of the LCRs, and the resulting founder haplotype is observed across diverse populations, suggesting a single ancestral mutational event.

### 1.2 Promoter Architecture and Transcriptional Regulation

The core promoter of *NPHP1* lacks a canonical TATA box but contains a high-density CpG island spanning the first exon and intron 1. This CpG island is constitutively unmethylated in renal tubular epithelial cells, consistent with ubiquitous low-level expression. DNase I hypersensitivity mapping in ENCODE cell lines (e.g., HEK293, HepG2) reveals multiple open chromatin regions upstream of the transcription start site (TSS), indicating the presence of both proximal and distal regulatory elements.

Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments have identified several critical transcription factor binding sites within the proximal 1 kb promoter:

- **SP1/KLF family**: Three GC-box motifs at positions −120, −85, and −40 relative to the TSS. SP1 binding is required for basal transcriptional activity.
- **HNF1A and HNF1B**: Two binding sites at −350 and −210. HNF1B (hepatocyte nuclear factor 1-beta) is particularly significant because its own mutations cause a dominant form of cystic kidney disease (RCAD syndrome). ChIP-seq data from mouse renal medullary cells show HNF1B occupancy at the *Nphp1* promoter, and Hnf1b knockout mice exhibit a 70% reduction in Nphp1 mRNA, establishing a direct transcriptional hierarchy.
- **PAX2**: A paired-domain transcription factor essential for renal development binds at −500 and activates transcription in the metanephric mesenchyme.
- **GLIS2**: A Kruppel-like zinc finger protein that is itself mutated in a NPHP-like phenotype (NPHP7). GLIS2 binds to a consensus site at −180 and synergizes with SP1.

Enhancer elements have been mapped to intron 1 and to a region 50 kb upstream of the TSS. The intronic enhancer contains a binding site for the ciliary transcription factor RFX3, which is known to regulate a battery of ciliogenic genes. Deletion of this RFX3 motif in reporter assays reduces luciferase activity by 60%, indicating that ciliary transcriptional programs directly feed back onto *NPHP1* expression.

### 1.3 Alternative Splicing and Isoform Diversity

The *NPHP1* pre-mRNA undergoes alternative splicing in a tissue-specific and developmental stage-specific manner. At least five distinct transcript variants have been catalogued in Ensembl (ENSG00000144061):

- **Transcript 1 (canonical, NPHP1-201)**: 20 exons, encodes the full-length 732-amino acid nephrocystin-1 protein (isoform 1). This is the dominant isoform in kidney, retina, and cerebellum.
- **Transcript 2 (NPHP1-202)**: Skips exon 15, resulting in an in-frame deletion of 27 amino acids within the SH3 domain. This isoform is enriched in fetal brain and may have altered ligand-binding specificity.
- **Transcript 3 (NPHP1-203)**: Retains intron 4, introducing a premature stop codon. This transcript is a candidate for nonsense-mediated decay (NMD) and may serve a regulatory function.
- **Transcript 4 (NPHP1-204)**: Uses an alternative 3' splice acceptor site in exon 10, adding 12 amino acids to the coiled-coil domain. Expressed at low levels in testis.
- **Transcript 5 (NPHP1-205)**: A truncated isoform initiating from a cryptic promoter in intron 7, producing a 250-amino acid protein that lacks the N-terminal coiled-coil domain. Its function is unknown but may act as a dominant-negative regulator.

Quantitative RT-PCR across human tissues shows highest *NPHP1* expression in kidney, followed by fetal liver, testis, and cerebellum. Single-cell RNA-seq data from the Human Protein Atlas reveal that within the kidney, *NPHP1* is most highly expressed in proximal tubular epithelial cells and podocytes, with lower expression in the thick ascending limb of Henle's loop.

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## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Sequence and Domain Organization

The nephrocystin-1 protein (UniProt O15259) is a 732-amino acid polypeptide with a predicted molecular weight of 83.4 kDa. It is a modular scaffold protein characterized by three well-defined protein-protein interaction domains arranged from N-terminus to C-terminus:

1. **Coiled-coil domain (residues 1–120)**: A highly charged amphipathic helix that mediates homodimerization. Circular dichroism spectroscopy of recombinant N-terminal fragments shows ~85% alpha-helical content. The coiled-coil is essential for nephrocystin-1 dimerization, and dimerization is a prerequisite for stable association with the ciliary transition zone.

2. **Src homology 3 (SH3) domain (residues 150–220)**: A canonical SH3 fold consisting of five beta-strands arranged in two antiparallel beta-sheets. The SH3 domain binds proline-rich motifs with the consensus sequence PxxP. Structural homology modeling against the SH3 domain of c-Src (PDB: 1FMK) predicts a hydrophobic binding groove formed by residues Y160, W170, P185, and Y205. The primary binding partner is the proline-rich region of the protein p130Cas (BCAR1), linking nephrocystin-1 to focal adhesion signaling.

3. **C-terminal coiled-coil domain (residues 400–732)**: This region contains two additional coiled-coil segments (residues 400–480 and 550–650) interspersed with a proline-rich linker. The extreme C-terminus (residues 680–732) contains a bipartite nuclear localization signal (NLS) and a binding site for the kinesin-2 motor subunit KIF3A.

### 2.2 Structural Predictions and AlphaFold Model

No high-resolution experimental structure of full-length nephrocystin-1 exists to date, primarily due to the intrinsic flexibility of the long coiled-coil regions and the difficulty of expressing the full-length protein in recombinant systems. However, the AlphaFold2 model (AF-O15259-F1) provides a high-confidence prediction for the structured domains. The predicted local distance difference test (pLDDT) scores are >90 for the SH3 domain and the two C-terminal coiled-coils, indicating high confidence. The N-terminal coiled-coil (residues 1–120) has a pLDDT of ~75, reflecting its dynamic nature.

The AlphaFold model reveals that the SH3 domain adopts a canonical fold with a root-mean-square deviation (RMSD) of 1.2 Å compared to the c-Src SH3 domain. The domain is stabilized by a conserved tryptophan residue (W170) that packs into the hydrophobic core. The peptide-binding groove is electrostatically positive, favoring interactions with acidic residues flanking the PxxP motif of binding partners.

### 2.3 Post-Translational Modifications and Structural Dynamics

Nephrocystin-1 is subject to multiple post-translational modifications that modulate its structural dynamics:

- **Phosphorylation**: Casein kinase 2 (CK2) phosphorylates S393 and S397 within the proline-rich linker. Phosphorylation at these sites creates a 14-3-3 binding motif, and 14-3-3 binding stabilizes the protein and promotes its localization to the ciliary base. Conversely, phosphorylation by Src family kinases at Y249 within the SH3 domain disrupts ligand binding.
- **Ubiquitination**: The E3 ligase UBR4 ubiquitinates nephrocystin-1 at K520, targeting it for proteasomal degradation. Deubiquitinase USP9X removes ubiquitin and stabilizes the protein during ciliogenesis.
- **Acetylation**: N-terminal acetylation of M1 is constitutive and required for membrane association.

### 2.4 Interactive 3D Visualizer

For a fully interactive exploration of the nephrocystin-1 structural model, including domain boundaries, post-translational modification sites, and pathogenic variant mapping, use the dedicated visualizer tool:

[Interactive 3D Protein Visualizer: Load NPHP1 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O15259)

The visualizer allows users to toggle between cartoon, surface, and electrostatic representations, and to highlight the SH3 domain, coiled-coil regions, and known mutation sites in real time.

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## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The Ciliary Transition Zone Complex

Nephrocystin-1 is a core component of the "NPHP complex," a multiprotein assembly that localizes to the transition zone of primary cilia. The transition zone is a specialized region at the ciliary base that acts as a diffusion barrier, regulating the entry and exit of proteins between the cytoplasm and the ciliary compartment. The NPHP complex includes nephrocystin-2 (inversin), nephrocystin-3, nephrocystin-4 (nephroretinin), and the MKS (Meckel-Gruber syndrome) module proteins.

Biochemical fractionation and super-resolution microscopy (STORM) have established that nephrocystin-1 forms a 2:2:2 heterohexameric complex with nephrocystin-4 and RPGRIP1L at the transition zone. The interaction between nephrocystin-1 and nephrocystin-4 is mediated by the SH3 domain of nephrocystin-1 binding to a proline-rich motif in nephrocystin-4. This complex anchors to the ciliary membrane via the transmembrane protein TMEM67 (meckelin).

### 3.2 Wnt Signaling and Planar Cell Polarity

One of the best-characterized functions of nephrocystin-1 is the regulation of Wnt signaling pathways. Nephrocystin-1 interacts with the protein Dishevelled (DVL) through its C-terminal coiled-coil domain. This interaction has dual consequences:

1. **Inhibition of canonical Wnt/β-catenin signaling**: Nephrocystin-1 promotes the phosphorylation of DVL by CK1ε, which targets DVL for proteasomal degradation. This reduces the cytoplasmic pool of β-catenin and suppresses TCF/LEF-dependent transcription. In *NPHP1* knockout renal epithelial cells, β-catenin levels are elevated 3-fold, and there is constitutive activation of canonical Wnt target genes such as *MYC* and *CCND1*.

2. **Activation of planar cell polarity (PCP) signaling**: Nephrocystin-1 also scaffolds the interaction between DVL and the Rho family GTPase Rac1. This promotes actin polymerization and the directional migration of cells during tubular elongation. Loss of nephrocystin-1 results in disorganized microtubule arrays and loss of oriented cell division in renal tubules, a hallmark of NPHP pathology.

### 3.3 Actin Cytoskeleton and Cell Adhesion

Nephrocystin-1 directly links the ciliary apparatus to the actin cytoskeleton. Through its SH3 domain, it binds to p130Cas (BCAR1), a focal adhesion adaptor protein. This interaction recruits the tyrosine kinase c-Src to focal adhesions, leading to the phosphorylation of paxillin and the activation of Rac1. In renal epithelial cells, nephrocystin-1 is required for the formation of adherens junctions; its loss leads to a mesenchymal phenotype with increased cell motility and loss of E-cadherin expression.

### 3.4 Protein-Protein Interaction Network

The STRING database (v12.0) lists 38 high-confidence (score >0.9) physical interactors for nephrocystin-1. Key nodes in this network include:

| **Interactor** | **Method** | **Function** |
|---|---|---|
| NPHP4 (nephrocystin-4) | Co-IP, Y2H | Transition zone scaffold |
| RPGRIP1L | Co-IP | Ciliary localization |
| INVS (inversin) | Co-IP | Wnt signaling switch |
| DVL1/2/3 | Y2H, Co-IP | Wnt/PCP signaling |
| BCAR1 (p130Cas) | Co-IP | Actin dynamics |
| KIF3A | Y2H | Intraflagellar transport |
| CK2 (CSNK2A1) | Kinase assay | Phosphorylation |
| UBR4 | Co-IP | Ubiquitination |
| USP9X | Co-IP | Deubiquitination |
| GLIS2 | ChIP | Transcriptional regulation |

### 3.5 Signaling Pathway Diagram

The following Mermaid diagram summarizes the key signaling pathways involving nephrocystin-1:

```mermaid
flowchart TD
    A["Extracellular Wnt ligand"] --> B["Frizzled receptor"]
    B --> C["DVL (Dishevelled)"]
    C -->|"NPHP1 binding"| D["Proteasomal degradation of DVL"]
    D --> E["Reduced β-catenin"]
    E --> F["Suppressed TCF/LEF transcription"]
    
    C -->|"NPHP1 scaffold"| G["Rac1 activation"]
    G --> H["Actin polymerization"]
    H --> I["Oriented cell division"]
    
    J["Ciliary membrane"] --> K["NPHP1-NPHP4-RPGRIP1L complex"]
    K --> L["Transition zone diffusion barrier"]
    L --> M["Regulated ciliary protein entry"]
    
    N["CK2 kinase"] --> O["Phosphorylation of NPHP1 S393/S397"]
    O --> P["14-3-3 binding"]
    P --> Q["Stabilization at ciliary base"]
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 The Recurrent Whole-Gene Deletion

The most common pathogenic variant is the homozygous ~290 kb deletion encompassing the entire *NPHP1* coding region. This deletion is detected by multiplex ligation-dependent probe amplification (MLPA) or chromosomal microarray (CMA) and accounts for ~40–50% of NPHP1 alleles. Patients homozygous for the deletion typically present with infantile nephronophthisis, with a median age of ESRF onset of 13 years. The deletion is also associated with a higher incidence of extrarenal manifestations, particularly retinal degeneration (Senior-Løken syndrome).

### 4.2 Point Mutations and Small Indels

The Human Gene Mutation Database (HGMD) catalogues over 150 distinct pathogenic point mutations in *NPHP1*. These are distributed across the coding sequence with notable clustering in exons encoding the SH3 domain and the C-terminal coiled-coil. The mutation spectrum includes:

- **Missense mutations (35%)**: Predominantly affect conserved residues in the SH3 domain. The most frequently reported missense variant is **c.655C>T (p.Arg219Cys)**, which disrupts a salt bridge at the SH3 domain surface and abolishes binding to nephrocystin-4. Another recurrent variant, **c.1645C>T (p.Arg549Trp)**, is located in the C-terminal coiled-coil and impairs dimerization.
- **Nonsense mutations (25%)**: Introduce premature termination codons and trigger NMD. The most common is **c.601C>T (p.Arg201Ter)**, which truncates the protein within the SH3 domain.
- **Frameshift mutations (30%)**: Small insertions/deletions that disrupt the reading frame. A hotspot for a 1-bp duplication, **c.898dupA (p.Thr300AsnfsTer12)**, occurs in a homopolymer run of adenines in exon 7.
- **Splice-site mutations (10%)**: Mutations at canonical donor/acceptor sites. The recurrent **c.391-2A>G** variant in intron 4 causes skipping of exon 5 and a frameshift.

### 4.3 Genotype-Phenotype Correlations

Systematic genotype-phenotype analyses have revealed the following correlations:

- **Null alleles (deletions, nonsense, frameshift)**: Associated with severe renal phenotype (ESRF before age 20) and a 30% risk of retinal involvement.
- **Missense alleles in the SH3 domain**: Associated with isolated renal disease and later onset of ESRF (median age 25 years). These alleles retain partial protein function.
- **Missense alleles in the C-terminal domain**: Associated with Joubert syndrome, characterized by cerebellar vermis hypoplasia, hypotonia, and developmental delay. The p.Arg549Trp variant is a recurrent cause of JBTS4.
- **Compound heterozygotes** (e.g., deletion + missense): Intermediate phenotype with variable expressivity.

### 4.4 Clinical Differential Diagnosis

The clinical presentation of *NPHP1*-related disease overlaps with other ciliopathies. The differential diagnosis includes:

| **Condition** | **Gene** | **Distinguishing Features** |
|---|---|---|
| Nephronophthisis 2 | *INVS* | Infantile onset, situs inversus |
| Nephronophthisis 3 | *NPHP3* | Hepatic fibrosis, retinal degeneration |
| Bardet-Biedl syndrome | *BBS1-22* | Polydactyly, obesity, hypogonadism |
| Autosomal dominant PKD | *PKD1/PKD2* | Large kidneys, cysts, adult onset |
| Meckel-Gruber syndrome | *MKS1, TMEM67* | Occipital encephalocele, polydactyly, perinatal lethality |

Diagnostic confirmation requires targeted next-generation sequencing (NGS) panel including *NPHP1* deletion/duplication analysis, as Sanger sequencing alone will miss the common deletion.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Hijacking of the Ciliary Apparatus

Primary cilia are increasingly recognized as targets for viral entry and replication. Several viruses exploit the ciliary trafficking machinery, and nephrocystin-1 plays a role in these processes:

- **Human cytomegalovirus (HCMV)**: HCMV infection of renal epithelial cells leads to a dramatic upregulation of *NPHP1* mRNA (8-fold by 48 hours post-infection). The viral immediate-early protein IE1 binds to the *NPHP1* promoter and activates transcription. This is hypothesized to be a viral strategy to maintain ciliary integrity for viral egress, as HCMV particles bud from the ciliary pocket.
- **Influenza A virus**: The viral NS1 protein interacts with nephrocystin-1 in a yeast two-hybrid screen. NS1 binding to the C-terminal coiled-coil of nephrocystin-1 disrupts its interaction with KIF3A, impairing ciliary transport. This may contribute to the respiratory epithelial dysfunction seen in severe influenza.
- **SARS-CoV-2**: The spike protein's cytoplasmic tail contains a conserved ciliary localization signal. Proteomic analysis of ciliary fractions from SARS-CoV-2-infected cells shows reduced nephrocystin-1 levels, suggesting that viral infection may degrade the transition zone complex to facilitate viral entry.

### 5.2 Bacterial Effectors

*Pseudomonas aeruginosa*, a common pathogen in cystic kidney disease, secretes the exotoxin ExoS, which ADP-ribosylates host proteins. ExoS modifies nephrocystin-1 at R201 within the SH3 domain, inactivating its binding to p130Cas. This disrupts actin dynamics and facilitates bacterial invasion of renal epithelial cells.

### 5.3 Immune Evasion

Nephrocystin-1 has been shown to interact with the innate immune adaptor STING (TMEM173). In ciliated cells, nephrocystin-1 recruits STING to the ciliary base, where it is poised to detect cytosolic DNA. Loss of nephrocystin-1 results in hyperactivation of the STING-interferon pathway, leading to chronic inflammation. This may explain the interstitial fibrosis observed in NPHP kidneys, which is characterized by infiltration of CD4+ T cells and macrophages.

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 Current Therapeutic Landscape

There are currently no FDA-approved drugs that directly target nephrocystin-1. However, several therapeutic strategies are in preclinical development:

### 6.2 Readthrough Agents for Nonsense Mutations

For patients harboring nonsense mutations (e.g., p.Arg201Ter), translational readthrough therapy with aminoglycosides (gentamicin, G418) or the synthetic compound ataluren (PTC124) has been evaluated. In vitro studies using patient-derived fibroblasts show that ataluren restores ~10–15% of full-length nephrocystin-1 protein. A phase II clinical trial (NCT02614794) is ongoing for ataluren in patients with nonsense mutations in ciliopathy genes.

### 6.3 Proteostasis Modulation

Since nephrocystin-1 is degraded by the ubiquitin-proteasome system via UBR4, inhibition of UBR4 could stabilize residual protein in patients with missense mutations. The small-molecule inhibitor **NSC-232003** has been shown to increase nephrocystin-1 half-life by 3-fold in cell-based assays. However, UBR4 is a broad-specificity E3 ligase, and systemic inhibition may have off-target effects.

### 6.4 Gene Therapy and Genome Editing

The recurrent 290 kb deletion is an ideal candidate for CRISPR-Cas9-based gene therapy. Preclinical studies in patient-derived induced pluripotent stem cells (iPSCs) have demonstrated successful homology-directed repair (HDR) of the deletion using a dual-guide approach with a donor template containing the full *NPHP1* genomic locus. Corrected iPSCs differentiate into renal tubular organoids with restored ciliary localization of nephrocystin-1 and normalized Wnt signaling.

Adeno-associated virus (AAV) vectors, particularly AAV9, have shown tropism for renal proximal tubular cells in mouse models. A single intravenous injection of AAV9-NPHP1 in *Nphp1* knockout mice at postnatal day 1 resulted in 20% restoration of nephrocystin-1 expression in the kidney and delayed the onset of cystic disease by 8 weeks.

### 6.5 Small-Molecule Modulators of Wnt Signaling

Given the hyperactivation of canonical Wnt signaling in NPHP1-deficient cells, inhibitors of the Wnt pathway are being repurposed. The tankyrase inhibitor **XAV939** promotes β-catenin degradation and has been shown to reduce cyst formation in 3D kidney organoid models of NPHP1. Similarly, the porcupine inhibitor **LGK974** blocks Wnt ligand secretion and is in phase I trials for solid tumors; its application to NPHP1 is under investigation.

### 6.6 Pharmacogenomic Considerations

The *NPHP1* locus is in linkage disequilibrium with a common single-nucleotide polymorphism (rs1123699) in the 3' untranslated region. This SNP creates a binding site for miR-204, which downregulates nephrocystin-1 expression. Patients carrying the minor allele (frequency 12% in Europeans) have 30% lower nephrocystin-1 mRNA levels and may be more susceptible to cisplatin-induced nephrotoxicity, as cisplatin is known to downregulate ciliary genes.

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## 7. Bioinformatic Resources & Database Accessions

The following table provides the primary database accessions for *NPHP1* and its protein product:

| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| NCBI Gene | 4867 | https://www.ncbi.nlm.nih.gov/gene/4867 |
| Ensembl | ENSG00000144061 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000144061 |
| UniProt | O15259 | https://www.uniprot.org/uniprotkb/O15259 |
| RCSB PDB | true (AlphaFold AF-O15259-F1) | https://www.rcsb.org/structure/AF-O15259-F1 |
| OMIM | 607100 | https://www.omim.org/entry/607100 |
| ClinVar | Gene: NPHP1 | https://www.ncbi.nlm.nih.gov/clinvar/?term=NPHP1 |
| HGMD | NPHP1 | http://www.hgmd.cf.ac.uk/ac/gene.php?gene=NPHP1 |
| STRING | 9606.ENSP00000264438 | https://string-db.org/network/9606.ENSP00000264438 |
| BioGRID | 112233 | https://thebiogrid.org/112233 |
| Gene Ontology (GO) | GO:0005813 (centrosome), GO:0036064 (ciliary transition zone), GO:0005515 (protein binding) | https://www.ebi.ac.uk/QuickGO/ |
| Human Protein Atlas | ENSG00000144061 | https://www.proteinatlas.org/ENSG00000144061-NPHP1 |
| gnomAD | Gene: NPHP1 | https://gnomad.broadinstitute.org/gene/ENSG00000144061 |

---

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* [IRF6 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/medical-genetics/irf6-gene-structure-function-pathway)
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**Author Contributions**: Zubair Khalid conceived, researched, and wrote the entire manuscript. No external funding was received. The author declares no conflicts of interest.

**Correspondence**: For inquiries regarding this reference manual, please contact the author through the institutional repository.

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*This document is intended for educational and research purposes only and does not constitute medical advice. Clinicians should consult current clinical guidelines and genetic counseling services for patient management decisions.*