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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:5,879,505-5,992,473)mRNA (may differ from genome)Protein (911 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold

-  Comments and Description Text from UniProtKB
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="";

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: NPHP4
Diseases sorted by gene-association score: nephronophthisis 4* (1360), senior-loken syndrome 4* (1330), nephronophthisis* (339), nephronophthisis 16* (202), senior-loken syndrome-1* (129), cogan syndrome (26), ciliopathy (17), nephronophthisis 1, juvenile (15), nephronophthisis 2, infantile (11), cystic kidney disease (10), senior-løken syndrome (8), renal fibrosis (6), heterotaxy (5), asphyxiating thoracic dystrophy (4), retinal degeneration (4), meckel syndrome 1 (4), retinitis pigmentosa (3), bardet-biedl syndrome (2), leber congenital amaurosis (2), eye disease (2), joubert syndrome 1 (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.65 RPKM in Pituitary
Total median expression: 162.86 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -135.90268-0.507 Picture PostScript Text

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
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005198 structural molecule activity
GO:0005515 protein binding

Biological Process:
GO:0007165 signal transduction
GO:0007632 visual behavior
GO:0030036 actin cytoskeleton organization
GO:0030317 flagellated sperm motility
GO:0035329 hippo signaling
GO:0035845 photoreceptor cell outer segment organization
GO:0045494 photoreceptor cell maintenance
GO:0060041 retina development in camera-type eye
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0097711 ciliary basal body docking
GO:0098609 cell-cell adhesion
GO:1903348 positive regulation of bicellular tight junction assembly

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005911 cell-cell junction
GO:0005923 bicellular tight junction
GO:0005929 cilium
GO:0030054 cell junction
GO:0032391 photoreceptor connecting cilium
GO:0035869 ciliary transition zone
GO:0036064 ciliary basal body
GO:0042995 cell projection
GO:0097470 ribbon synapse
GO:0097546 ciliary base
GO:0097730 non-motile cilium

-  Descriptions from all associated GenBank mRNAs
  AY118228 - Homo sapiens nephrocystin-4 (NPHP4) mRNA, complete cds.
AK124074 - Homo sapiens cDNA FLJ42080 fis, clone SYNOV4000249, highly similar to Nephrocystin-4.
BC040520 - Homo sapiens nephronophthisis 4, mRNA (cDNA clone MGC:39505 IMAGE:5295140), complete cds.
AB014573 - Homo sapiens mRNA for KIAA0673 protein, partial cds.
AF537130 - Homo sapiens nephronophthisis 4 (NPHP4) mRNA, complete cds.
AK314326 - Homo sapiens cDNA, FLJ95086.
KJ904095 - Synthetic construct Homo sapiens clone ccsbBroadEn_13489 NPHP4 gene, encodes complete protein.
KR710924 - Synthetic construct Homo sapiens clone CCSBHm_00018184 NPHP4 (NPHP4) mRNA, encodes complete protein.
KR710925 - Synthetic construct Homo sapiens clone CCSBHm_00018187 NPHP4 (NPHP4) mRNA, encodes complete protein.
KR710926 - Synthetic construct Homo sapiens clone CCSBHm_00018190 NPHP4 (NPHP4) mRNA, encodes complete protein.
AL117405 - Homo sapiens mRNA; cDNA DKFZp434K1235 (from clone DKFZp434K1235); partial cds.
AK128182 - Homo sapiens cDNA FLJ46306 fis, clone TESTI4038758.
JD489874 - Sequence 470898 from Patent EP1572962.
JD100786 - Sequence 81810 from Patent EP1572962.
JD214547 - Sequence 195571 from Patent EP1572962.
JD256461 - Sequence 237485 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O75161 (Reactome details) participates in the following event(s):

R-HSA-2059926 NPHP4 protein binds LATS proteins
R-HSA-5626681 Recruitment of transition zone proteins
R-HSA-5638009 CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
R-HSA-5617816 RAB3IP stimulates nucleotide exchange on RAB8A
R-HSA-2028269 Signaling by Hippo
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-162582 Signal Transduction
R-HSA-5617833 Cilium Assembly
R-HSA-1852241 Organelle biogenesis and maintenance

-  Other Names for This Gene
  Alternate Gene Symbols: BC040520, ENST00000622020.1, ENST00000622020.2, ENST00000622020.3, KIAA0673, NPHP4_HUMAN, O75161, uc057bsj.1
UCSC ID: ENST00000622020.4
RefSeq Accession: NR_111987
Protein: O75161 (aka NPHP4_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene NPHP4:
nephron-ov (Nephronophthisis-Related Ciliopathies)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.