NPHP3
nephrocystin 3, the group of Cilia and flagella associated|Tetratricopeptide repeat domain containing
Basic information
Region (hg38): 3:132680609-132722432
Links
Phenotypes
GenCC
Source:
- nephronophthisis 3 (Definitive), mode of inheritance: AR
- NPHP3-related Meckel-like syndrome (Supportive), mode of inheritance: AR
- Senior-Loken syndrome (Supportive), mode of inheritance: AR
- late-onset nephronophthisis (Supportive), mode of inheritance: AR
- nephronophthisis 2 (Supportive), mode of inheritance: AR
- renal-hepatic-pancreatic dysplasia (Supportive), mode of inheritance: AR
- nephronophthisis 3 (Strong), mode of inheritance: AR
- nephronophthisis (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Nephronophthisis 3; Meckel syndrome, type 7; Renal-hepatic-pancreatic dysplasia 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 | Gastrointestinal; Hematologic; Musculoskeletal; Renal | 8874114; 12872122; 18371931; 19303681; 19177160; 20007846; 21068128; 21642631;21866095 |
| Liver-kidney transplantation has been described |
ClinVar
This is a list of variants' phenotypes submitted to
- Nephronophthisis (50 variants)
- not provided (15 variants)
- Nephronophthisis 3 (11 variants)
- NPHP3-related Meckel-like syndrome (8 variants)
- Nephronophthisis 3;Renal-hepatic-pancreatic dysplasia 1;NPHP3-related Meckel-like syndrome (2 variants)
- Nephronophthisis 3;NPHP3-related Meckel-like syndrome;Renal-hepatic-pancreatic dysplasia 1 (2 variants)
- Renal-hepatic-pancreatic dysplasia 1;NPHP3-related Meckel-like syndrome;Nephronophthisis 3 (1 variants)
- Renal-hepatic-pancreatic dysplasia 1;Nephronophthisis 3;NPHP3-related Meckel-like syndrome (1 variants)
- Renal-hepatic-pancreatic dysplasia 1 (1 variants)
- Joubert syndrome and related disorders (1 variants)
- NPHP3-related Meckel-like syndrome;Renal-hepatic-pancreatic dysplasia 1;Nephronophthisis 3 (1 variants)
- Renal-hepatic-pancreatic dysplasia (1 variants)
- NPHP3-related disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPHP3 gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 156 | 166 | ||||
| missense | 454 | 468 | ||||
| nonsense | 28 | 11 | 40 | |||
| start loss | 2 | |||||
| frameshift | 31 | 13 | 44 | |||
| inframe indel | 7 | |||||
| splice donor/acceptor (+/-2bp) | 15 | 22 | ||||
| splice region | 24 | 34 | 5 | 63 | ||
| non coding | 34 | 135 | 50 | 219 | ||
| Total | 67 | 47 | 504 | 298 | 52 |
Highest pathogenic variant AF is 0.0000986
Variants in NPHP3
This is a list of pathogenic ClinVar variants found in the NPHP3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-132680697-A-G | Renal-hepatic-pancreatic dysplasia 1 • NPHP3-related Meckel-like syndrome • Nephronophthisis 3 | Uncertain significance (Jan 13, 2018) | ||
| 3-132680722-T-C | Nephronophthisis 3 • NPHP3-related Meckel-like syndrome • Renal-hepatic-pancreatic dysplasia 1 | Uncertain significance (Jan 12, 2018) | ||
| 3-132680726-T-A | Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 • NPHP3-related Meckel-like syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-132680734-C-T | Nephronophthisis 3 • Renal-hepatic-pancreatic dysplasia 1 • NPHP3-related Meckel-like syndrome | Conflicting classifications of pathogenicity (Jan 12, 2018) | ||
| 3-132680789-T-C | NPHP3-related Meckel-like syndrome • Nephronophthisis 3 • Renal-hepatic-pancreatic dysplasia 1 | Uncertain significance (Jan 12, 2018) | ||
| 3-132680812-G-A | Renal-hepatic-pancreatic dysplasia 1 • NPHP3-related Meckel-like syndrome • Nephronophthisis 3 | Uncertain significance (Jan 12, 2018) | ||
| 3-132680816-T-C | Renal-hepatic-pancreatic dysplasia 1 • NPHP3-related Meckel-like syndrome • Nephronophthisis 3 | Uncertain significance (Jan 15, 2018) | ||
| 3-132680832-A-C | Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 • NPHP3-related Meckel-like syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-132680890-A-G | Renal-hepatic-pancreatic dysplasia 1 • NPHP3-related Meckel-like syndrome • Nephronophthisis 3 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 3-132680984-G-A | Renal-hepatic-pancreatic dysplasia 1 • NPHP3-related Meckel-like syndrome • Nephronophthisis 3 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 3-132681058-G-T | Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 • NPHP3-related Meckel-like syndrome | Uncertain significance (Jan 12, 2018) | ||
| 3-132681095-C-T | NPHP3-related Meckel-like syndrome • Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 | Conflicting classifications of pathogenicity (May 25, 2021) | ||
| 3-132681125-C-T | Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 • NPHP3-related Meckel-like syndrome | Benign/Likely benign (May 26, 2021) | ||
| 3-132681126-G-A | Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 • NPHP3-related Meckel-like syndrome | Uncertain significance (Jan 13, 2018) | ||
| 3-132681151-C-T | Nephronophthisis 3 • NPHP3-related Meckel-like syndrome • Renal-hepatic-pancreatic dysplasia 1 | Conflicting classifications of pathogenicity (Sep 10, 2021) | ||
| 3-132681218-G-A | Nephronophthisis 3 • NPHP3-related Meckel-like syndrome • Renal-hepatic-pancreatic dysplasia 1 | Uncertain significance (Jan 13, 2018) | ||
| 3-132681237-G-C | Likely benign (May 20, 2021) | |||
| 3-132681253-G-A | NPHP3-related Meckel-like syndrome • Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis 3 | Benign (May 24, 2021) | ||
| 3-132681255-A-AT | Nephronophthisis • Meckel-Gruber syndrome • Renal-hepatic-pancreatic dysplasia 1 | Uncertain significance (Jun 14, 2016) | ||
| 3-132681256-TTC-T | Renal-hepatic-pancreatic dysplasia 1 • Meckel-Gruber syndrome • Nephronophthisis | Uncertain significance (Jun 14, 2016) | ||
| 3-132681257-TC-T | Renal-hepatic-pancreatic dysplasia 1 • Nephronophthisis • Meckel-Gruber syndrome | Uncertain significance (Jun 14, 2016) | ||
| 3-132681258-CT-C | Benign (May 13, 2021) | |||
| 3-132681258-CTT-C | Meckel-Gruber syndrome • Nephronophthisis • Renal-hepatic-pancreatic dysplasia 1 | Conflicting classifications of pathogenicity (May 14, 2021) | ||
| 3-132681258-C-CT | Benign (Jun 04, 2021) | |||
| 3-132681284-G-C | NPHP3-related Meckel-like syndrome • Nephronophthisis 3 • Renal-hepatic-pancreatic dysplasia 1 | Uncertain significance (Jan 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NPHP3 | protein_coding | protein_coding | ENST00000337331 | 27 | 164318 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 9.84e-16 | 1.00 | 125511 | 0 | 237 | 125748 | 0.000943 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.864 | 627 | 691 | 0.908 | 0.0000352 | 8672 |
| Missense in Polyphen | 179 | 205.57 | 0.87075 | 2578 | ||
| Synonymous | 1.41 | 228 | 257 | 0.888 | 0.0000129 | 2522 |
| Loss of Function | 4.10 | 38 | 76.7 | 0.495 | 0.00000398 | 923 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00134 | 0.00134 |
| Ashkenazi Jewish | 0.000198 | 0.000198 |
| East Asian | 0.00163 | 0.00163 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.00120 | 0.00119 |
| Middle Eastern | 0.00163 | 0.00163 |
| South Asian | 0.000751 | 0.000752 |
| Other | 0.000992 | 0.000978 |
dbNSFP
Source:
- Function
- FUNCTION: Required for normal ciliary development and function. Inhibits disheveled-1-induced canonical Wnt-signaling activity and may also play a role in the control of non-canonical Wnt signaling which regulates planar cell polarity. Probably acts as a molecular switch between different Wnt signaling pathways. Required for proper convergent extension cell movements. {ECO:0000269|PubMed:18371931}.;
- Disease
- DISEASE: Renal-hepatic-pancreatic dysplasia 1 (RHPD1) [MIM:208540]: A disease characterized by cystic malformations of the kidneys, liver, and pancreas. The pathological findings consist of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates. {ECO:0000269|PubMed:18371931}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 7 (MKS7) [MIM:267010]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:18371931}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Trafficking of myristoylated proteins to the cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.196
Intolerance Scores
- loftool
- 0.153
- rvis_EVS
- -1.01
- rvis_percentile_EVS
- 8.2
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.683
- ghis
- 0.572
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.747
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nphp3
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton 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); craniofacial phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- nphp3
- Affected structure
- trunk
- Phenotype tag
- abnormal
- Phenotype quality
- curved ventral
Gene ontology
- Biological process
- kidney development;heart looping;atrial septum development;determination of left/right symmetry;Wnt signaling pathway;lung development;determination of pancreatic left/right asymmetry;photoreceptor cell maintenance;maintenance of animal organ identity;convergent extension involved in gastrulation;cilium assembly;epithelial cilium movement involved in determination of left/right asymmetry;kidney morphogenesis;determination of intestine left/right asymmetry;determination of stomach left/right asymmetry;determination of liver left/right asymmetry;ureter development;negative regulation of canonical Wnt signaling pathway;regulation of Wnt signaling pathway, planar cell polarity pathway;regulation of planar cell polarity pathway involved in neural tube closure
- Cellular component
- cytosol;cilium
- Molecular function
- protein binding