NPHP1
nephrocystin 1, the group of NPHP complex
Basic information
Region (hg38): 2:110122311-110205066
Previous symbols: [ "NPH1" ]
Links
Phenotypes
GenCC
Source:
- nephronophthisis 1 (Definitive), mode of inheritance: AR
- Joubert syndrome with renal defect (Moderate), mode of inheritance: AR
- Senior-Loken syndrome (Supportive), mode of inheritance: AR
- Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
- nephronophthisis 1 (Supportive), mode of inheritance: AR
- Joubert syndrome with renal defect (Supportive), mode of inheritance: AR
- Joubert syndrome with renal defect (Definitive), mode of inheritance: AR
- nephronophthisis 1 (Strong), mode of inheritance: AR
- nephronophthisis 1 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Joubert syndrome 4; Nephronophthisis 1; Senior-Loken syndrome 1 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Hematologic; Neurologic; Ophthalmologic; Renal | 14823504; 13763238; 13910672; 9326933; 9361039; 9856524; 10196704; 15138899; 16155189; 16571882; 20301500; 20454808; 20652329; 21068128; 21258817; 21866095; 23559409 |
| The conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Renal transplant has been described, though nephrotic syndrome may recur post-transplantation |
ClinVar
This is a list of variants' phenotypes submitted to
- Nephronophthisis (715 variants)
- Joubert_syndrome_with_renal_defect (249 variants)
- Nephronophthisis_1 (223 variants)
- Senior-Loken_syndrome_1 (210 variants)
- not_provided (166 variants)
- NPHP1-related_disorder (101 variants)
- Inborn_genetic_diseases (82 variants)
- not_specified (30 variants)
- Retinal_dystrophy (9 variants)
- Joubert_syndrome_and_related_disorders (5 variants)
- Kidney_disorder (3 variants)
- Leber_congenital_amaurosis (1 variants)
- Intellectual_disability,_X-linked_102 (1 variants)
- Joubert_syndrome (1 variants)
- Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
- Renal_dysplasia_and_retinal_aplasia (1 variants)
- Bardet-Biedl_syndrome_1 (1 variants)
- Joubert_syndrome_1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPHP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001128178.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 177 | 187 | ||||
| missense | 314 | 18 | 334 | |||
| nonsense | 17 | 19 | 36 | |||
| start loss | 1 | 1 | 2 | |||
| frameshift | 35 | 24 | 60 | |||
| splice donor/acceptor (+/-2bp) | 30 | 39 | ||||
| Total | 60 | 75 | 327 | 195 | 1 |
Highest pathogenic variant AF is 0.000186907
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NPHP1 | protein_coding | protein_coding | ENST00000316534 | 20 | 82756 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.24e-17 | 0.428 | 125668 | 0 | 79 | 125747 | 0.000314 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.226 | 369 | 381 | 0.967 | 0.0000192 | 4814 |
| Missense in Polyphen | 127 | 143.75 | 0.88347 | 1953 | ||
| Synonymous | 0.777 | 124 | 136 | 0.915 | 0.00000727 | 1365 |
| Loss of Function | 1.69 | 33 | 45.2 | 0.729 | 0.00000216 | 533 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00126 | 0.00126 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000490 | 0.000489 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000239 | 0.000237 |
| Middle Eastern | 0.000490 | 0.000489 |
| South Asian | 0.000267 | 0.000261 |
| Other | 0.000328 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Together with BCAR1 it may play a role in the control of epithelial cell polarity. Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling. May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development. In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Nephronophthisis 1 (NPHP1) [MIM:256100]: An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years. {ECO:0000269|PubMed:10839884}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Senior-Loken syndrome 1 (SLSN1) [MIM:266900]: A renal- retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269|PubMed:9856524}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 4 (JBTS4) [MIM:609583]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 4 is a phenotypically mild form. {ECO:0000269|PubMed:15138899, ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.178
Intolerance Scores
- loftool
- 0.993
- rvis_EVS
- 0.07
- rvis_percentile_EVS
- 58.96
Haploinsufficiency Scores
- pHI
- 0.109
- hipred
- N
- hipred_score
- 0.485
- ghis
- 0.477
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.541
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nphp1
- Phenotype
- endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype;
Zebrafish Information Network
- Gene name
- nphp1
- Affected structure
- pronephric proximal convoluted tubule
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- signal transduction;excretion;visual behavior;cell projection organization;actin cytoskeleton organization;spermatid differentiation;retina development in camera-type eye;ciliary basal body-plasma membrane docking;cell-cell adhesion;positive regulation of bicellular tight junction assembly
- Cellular component
- cytosol;cytoskeleton;cell-cell junction;adherens junction;bicellular tight junction;membrane;motile cilium;photoreceptor connecting cilium
- Molecular function
- structural molecule activity;protein binding