Human Gene NPHP3 (ENST00000337331.10) from GENCODE V44
  Description: Homo sapiens nephrocystin 3 (NPHP3), mRNA. (from RefSeq NM_153240)
RefSeq Summary (NM_153240): This gene encodes a protein containing a coiled-coil (CC) domain, a tubulin-tyrosine ligase (TTL) domain, and a tetratrico peptide repeat (TPR) domain. The encoded protein interacts with nephrocystin, it is required for normal ciliary development, and it functions in renal tubular development. Mutations in this gene are associated with nephronophthisis type 3, and also with renal-hepatic-pancreatic dysplasia, and Meckel syndrome type 7. Naturally occurring read-through transcripts exist between this gene and the downstream ACAD11 (acyl-CoA dehydrogenase family, member 11) gene. [provided by RefSeq, Feb 2011]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Gencode Transcript: ENST00000337331.10
Gencode Gene: ENSG00000113971.21
Transcript (Including UTRs)
   Position: hg38 chr3:132,680,609-132,722,409 Size: 41,801 Total Exon Count: 27 Strand: -
Coding Region
   Position: hg38 chr3:132,681,910-132,722,355 Size: 40,446 Coding Exon Count: 27 

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 (chr3:132,680,609-132,722,409)mRNA (may differ from genome)Protein (1330 aa)
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NPHP3_HUMAN
DESCRIPTION: RecName: Full=Nephrocystin-3;
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.
SUBUNIT: Interacts with NPHP1 and INVS/NPHP2. Interacts (when myristoylated) with UNC119 and UNC119B; interaction is required for localization to cilium. Interacts with CEP164.
SUBCELLULAR LOCATION: Cell projection, cilium. Note=Localization to cilium is mediated via interaction with UNC119 and UNC119B, which bind to the myristoyl moiety of the N-terminus.
TISSUE SPECIFICITY: Widely expressed at low level. Expressed in heart, placenta, liver, skeletal muscle, kidney and pancreas. Expressed at very low level in brain and lung.
DISEASE: Defects in NPHP3 are the cause of nephronophthisis type 3 (NPHP3) [MIM:604387]; also known as adolescent nephronophthisis. NPHP3 is a autosomal recessive disorder resulting in end-stage renal disease. It is characterized by polyuria, polydipsia, anemia. Onset of terminal renal failure occurr significantly later (median age, 19 years) than in juvenile nephronophthisis. Renal pathology is characterized by alterations of tubular basement membranes, tubular atrophy and dilation, sclerosing tubulointerstitial nephropathy, and renal cyst development predominantly at the corticomedullary junction.
DISEASE: Defects in NPHP3 are a cause of renal-hepatic-pancreatic dysplasia (RHPD) [MIM:208540]. RHPD is an autosomal recessive disorder with variable expression, and patients surviving the neonatal period progress to renal and hepatic failure which can be treated successfully with combined liver-kidney transplantation.
DISEASE: Defects in NPHP3 are the cause of Meckel syndrome type 7 (MKS7) [MIM:267010]. It is a form of Meckel syndrome, an autosomal recessive disorder. It is 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.
SIMILARITY: Contains 11 TPR repeats.
SEQUENCE CAUTION: Sequence=BAB70891.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAC02709.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAC04268.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: NPHP3
Diseases sorted by gene-association score: nephronophthisis 3* (1349), meckel syndrome 7* (1269), renal-hepatic-pancreatic dysplasia 1* (1230), renal-hepatic-pancreatic dysplasia* (909), nephronophthisis* (276), late-onset nephronophthisis* (247), senior-loken syndrome-1* (122), nphp3-related meckel syndrome* (100), nephronophthisis 2, infantile (15), nephronophthisis 1, juvenile (13), cystic kidney disease (11), bardet-biedl syndrome 15 (9), senior-løken syndrome (9), cogan syndrome (7), right atrial isomerism (7), encephalocele (6), bardet-biedl syndrome 13 (5), visceral heterotaxy (4), bardet-biedl syndrome 11 (4), retinitis pigmentosa (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • D002794 Choline
  • D003375 Coumestrol
  • D016572 Cyclosporine
  • D005492 Folic Acid
  • D008715 Methionine
  • D018817 N-Methyl-3,4-methylenedioxyamphetamine
  • C005961 bis(tri-n-butyltin)oxide
  • C015559 trimellitic anhydride

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 23.49 RPKM in Ovary
Total median expression: 439.44 RPKM



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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -18.6054-0.344 Picture PostScript Text
3' UTR -332.001301-0.255 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
  InterPro Domains: Graphical view of domain structure
IPR013026 - TPR-contain_dom
IPR011990 - TPR-like_helical
IPR019734 - TPR_repeat

Pfam Domains:
PF13176 - Tetratricopeptide repeat

ModBase Predicted Comparative 3D Structure on Q7Z494
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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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

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

Biological Process:
GO:0001822 kidney development
GO:0001947 heart looping
GO:0003283 atrial septum development
GO:0007368 determination of left/right symmetry
GO:0016055 Wnt signaling pathway
GO:0030324 lung development
GO:0035469 determination of pancreatic left/right asymmetry
GO:0045494 photoreceptor cell maintenance
GO:0048496 maintenance of animal organ identity
GO:0060027 convergent extension involved in gastrulation
GO:0060271 cilium assembly
GO:0060287 epithelial cilium movement involved in determination of left/right asymmetry
GO:0060993 kidney morphogenesis
GO:0071908 determination of intestine left/right asymmetry
GO:0071909 determination of stomach left/right asymmetry
GO:0071910 determination of liver left/right asymmetry
GO:0072189 ureter development
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:2000095 regulation of Wnt signaling pathway, planar cell polarity pathway
GO:2000167 regulation of planar cell polarity pathway involved in neural tube closure

Cellular Component:
GO:0005829 cytosol
GO:0005929 cilium
GO:0042995 cell projection


-  Descriptions from all associated GenBank mRNAs
  AB082531 - Homo sapiens mRNA for KIAA2000 protein.
AY257867 - Homo sapiens nephrocystin 3 splice variant (NPHP3) mRNA, partial cds.
BC063277 - Homo sapiens cDNA clone IMAGE:30334133, partial cds.
AL832877 - Homo sapiens mRNA; cDNA DKFZp667I223 (from clone DKFZp667I223).
CR749498 - Homo sapiens mRNA; cDNA DKFZp781K1312 (from clone DKFZp781K1312).
AL832863 - Homo sapiens mRNA; cDNA DKFZp667K242 (from clone DKFZp667K242).
AB056657 - Homo sapiens mRNA, possible morphine-related gene.
AK093012 - Homo sapiens cDNA FLJ35693 fis, clone SPLEN2019571, weakly similar to KINESIN LIGHT CHAIN.
AX747855 - Sequence 1380 from Patent EP1308459.
JD482639 - Sequence 463663 from Patent EP1572962.
JD435302 - Sequence 416326 from Patent EP1572962.
JD249791 - Sequence 230815 from Patent EP1572962.
JD148269 - Sequence 129293 from Patent EP1572962.
JD463782 - Sequence 444806 from Patent EP1572962.
JD478540 - Sequence 459564 from Patent EP1572962.
JD543230 - Sequence 524254 from Patent EP1572962.
JD537271 - Sequence 518295 from Patent EP1572962.
JD148270 - Sequence 129294 from Patent EP1572962.
JD463783 - Sequence 444807 from Patent EP1572962.
JD478541 - Sequence 459565 from Patent EP1572962.
JD543231 - Sequence 524255 from Patent EP1572962.
BC131729 - Homo sapiens nephronophthisis 3 (adolescent), mRNA (cDNA clone IMAGE:40124362).
AY257864 - Homo sapiens nephrocystin 3 (NPHP3) mRNA, complete cds.
AK092910 - Homo sapiens cDNA FLJ35591 fis, clone SPLEN2007647, weakly similar to KINESIN LIGHT CHAIN.
AX747803 - Sequence 1328 from Patent EP1308459.
AK094015 - Homo sapiens cDNA FLJ36696 fis, clone UTERU2008939, weakly similar to Plectonema boryanum kinesin light chain (KLC) gene.
AX748412 - Sequence 1937 from Patent EP1308459.
JD045834 - Sequence 26858 from Patent EP1572962.
BC172279 - Synthetic construct Homo sapiens clone IMAGE:100068973, MGC:198984 nephronophthisis 3 (adolescent) (NPHP3) mRNA, encodes complete protein.
AY257865 - Homo sapiens nephrocystin 3 splice variant (NPHP3) mRNA, partial cds.
AK055253 - Homo sapiens cDNA FLJ30691 fis, clone FCBBF2000591, weakly similar to KINESIN LIGHT CHAIN.
JD408233 - Sequence 389257 from Patent EP1572962.
AY257866 - Homo sapiens nephrocystin 3 splice variant (NPHP3) mRNA, partial cds.
AK055893 - Homo sapiens cDNA FLJ31331 fis, clone MAMGL1000056.
BC068082 - Homo sapiens nephronophthisis 3 (adolescent), mRNA (cDNA clone IMAGE:6213558), complete cds.
KJ902445 - Synthetic construct Homo sapiens clone ccsbBroadEn_11839 NPHP3 gene, encodes complete protein.

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

Protein Q7Z494 (Reactome details) participates in the following event(s):

R-HSA-5624130 Myristoylated NPHP3 translocates into the ciliary membrane
R-HSA-5624131 UNC119B binds myristoylated proteins
R-HSA-5624133 ARL3:GTP binds the UNC119B complex
R-HSA-5624138 Trafficking of myristoylated proteins to the cilium
R-HSA-5620920 Cargo trafficking to the periciliary membrane
R-HSA-5617833 Cilium Assembly
R-HSA-1852241 Organelle biogenesis and maintenance

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000337331.1, ENST00000337331.2, ENST00000337331.3, ENST00000337331.4, ENST00000337331.5, ENST00000337331.6, ENST00000337331.7, ENST00000337331.8, ENST00000337331.9, KIAA2000, NM_153240, NPHP3_HUMAN, Q5JPE3, Q5JPE6, Q68D99, Q6NVH3, Q7Z492, Q7Z493, Q7Z494, Q8N9R2, Q8NCM5, Q96N70, Q96NK2, uc003epe.1, uc003epe.2, uc003epe.3, uc003epe.4
UCSC ID: ENST00000337331.10
RefSeq Accession: NM_153240
Protein: Q7Z494 (aka NPHP3_HUMAN)
CCDS: CCDS3078.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene NPHP3:
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.