Human Gene NPHP4 (ENST00000622020.4) from GENCODE V44
Description: Involved in the organization of apical junctions in kidney cells together with NPHP1 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). (from UniProt O75161) RefSeq Summary (NR_111987): This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are associated with nephronophthisis type 4, a renal disease, and with Senior-Loken syndrome type 4, a combination of nephronophthisis and retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]. Gencode Transcript: ENST00000622020.4 Gencode Gene: ENSG00000131697.18 Transcript (Including UTRs) Position: hg38 chr1:5,879,505-5,992,473 Size: 112,969 Total Exon Count: 20 Strand: - Coding Region Position: hg38 chr1:5,879,505-5,986,289 Size: 106,785 Coding Exon Count: 19
ID:NPHP4_HUMAN DESCRIPTION: RecName: Full=Nephrocystin-4; AltName: Full=Nephroretinin; FUNCTION: Involved in the organization of apical junctions in kidney cells together with NPHP1 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). SUBUNIT: Interacts with NPHP1 and RPGRIP1L/NPHP8, and can bridge the interaction between those two proteins. Interacts with IQCB1; the interaction likely requires additional interactors. Interacts with RPGRIP1. Weakly interacts with CEP164. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body. Cytoplasm, cytoskeleton, centrosome. Cell junction, tight junction. Note=In cultured renal cells, it localizes diffusely in the cytoplasm but, as cells approach confluence, it accumulates to basolateral tight junctions. TISSUE SPECIFICITY: Expressed in kidney, skeletal muscle, heart and liver, and to a lesser extent in brain and lung. DISEASE: Defects in NPHP4 are the cause of nephronophthisis type 4 (NPHP4) [MIM:606966]; also known as familial juvenile nephronophthisis 4. NPHP4 is an autosomal recessive inherited disease resulting in end-stage renal disease at age ranging between 6 and 35 years. It is a progressive tubulo-interstitial kidney disorder characterized by polydipsia, polyuria, anemia and growth retardation. The most prominent histological features are modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. DISEASE: Note=Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. Overlapping clinical features include retinal degeneration, renal cystic disease, skeletal abnormalities, fibrosis of various organ, and a complex range of anatomical and functional defects of the central and peripheral nervous system. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, nephronophtisis, Senior-Loken syndrome, and Jeune asphyxiating thoracic dystrophy among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome, including NPHP4, influence the clinical outcome. DISEASE: Defects in NPHP4 are the cause of Senior-Loken syndrome type 4 (SLSN4) [MIM:606996]. SLSN is a renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney, with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. SIMILARITY: Belongs to the NPHP4 family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NPHP4";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Protein Domain and Structure Information
ModBase Predicted Comparative 3D Structure on O75161
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.