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Q00604 (NDP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Norrin
Alternative name(s):
Norrie disease protein
X-linked exudative vitreoretinopathy 2 protein
Gene names
Name:NDP
Synonyms:EVR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length133 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction.

Subunit structure

Interacts with FZD4. Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) By similarity. Oligomer; disulfide-linked. Ref.7

Subcellular location

Secreted Ref.7.

Tissue specificity

Expressed in the outer nuclear, inner nuclear and ganglion cell layers of the retina, and in fetal and adult brain. Ref.8

Involvement in disease

Norrie disease (ND) [MIM:310600]: Recessive disorder characterized by very early childhood blindness due to degenerative and proliferative changes of the neuroretina. Approximately 50% of patients show some form of progressive mental disorder, often with psychotic features, and about one-third of patients develop sensorineural deafness in the second decade. In addition, some patients have more complex phenotypes, including growth failure and seizure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40

Vitreoretinopathy, exudative 2 (EVR2) [MIM:305390]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.22 Ref.26 Ref.33 Ref.34 Ref.38 Ref.39

Sequence similarities

Contains 1 CTCK (C-terminal cystine knot-like) domain.

Ontologies

Keywords
   Biological processSensory transduction
Vision
Wnt signaling pathway
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDeafness
Disease mutation
   DomainSignal
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from direct assay PubMed 17955262. Source: BHF-UCL

canonical Wnt signaling pathway

Inferred from direct assay PubMed 15035989. Source: BHF-UCL

cell proliferation

Traceable author statement Ref.9. Source: ProtInc

cell-cell signaling

Traceable author statement Ref.9. Source: ProtInc

extracellular matrix-cell signaling

Inferred from electronic annotation. Source: Ensembl

nervous system development

Traceable author statement Ref.16. Source: ProtInc

placenta development

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15035989PubMed 17955262. Source: BHF-UCL

retina vasculature morphogenesis in camera-type eye

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Non-traceable author statement Ref.9. Source: ProtInc

signal transduction

Traceable author statement Ref.9. Source: ProtInc

vacuole organization

Traceable author statement Ref.29. Source: ProtInc

visual perception

Traceable author statement Ref.29. Source: ProtInc

   Cellular_componentcell surface

Inferred from direct assay PubMed 17955262. Source: BHF-UCL

extracellular matrix

Inferred from direct assay PubMed 15035989. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 17955262. Source: BHF-UCL

   Molecular_functionfrizzled binding

Inferred from physical interaction PubMed 17955262. Source: BHF-UCL

growth factor activity

Traceable author statement Ref.9. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 17955262PubMed 19837033. Source: IntAct

protein homodimerization activity

Inferred from physical interaction PubMed 17955262. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FZD4Q9ULV14EBI-2466352,EBI-2466380

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 133109Norrin
PRO_0000021794

Regions

Domain39 – 13294CTCK

Amino acid modifications

Disulfide bond39 ↔ 96 By similarity
Disulfide bond55 ↔ 110 By similarity
Disulfide bond65 ↔ 126 By similarity
Disulfide bond69 ↔ 128 By similarity
Disulfide bond? ↔ 131 By similarity

Natural variations

Natural variant131L → R in ND. Ref.11
VAR_005478
Natural variant161L → P in ND. Ref.30
VAR_016048
Natural variant181I → K in EVR2; the patient presented significant phenotypic heterogeneity between the two eyes. Ref.39
VAR_063998
Natural variant231D → E.
Corresponds to variant rs5952410 [ dbSNP | Ensembl ].
VAR_034137
Natural variant381R → C in ND and EVR2. Ref.31 Ref.33
VAR_063999
Natural variant391C → R in ND. Ref.12 Ref.38
VAR_005479
Natural variant411R → K in EVR2. Ref.26
VAR_005480
Natural variant411R → S in persistent fetal vasculature syndrome. Ref.38
VAR_064000
Natural variant421H → R in EVR2. Ref.26 Ref.38
VAR_005481
Natural variant431H → Q in ND. Ref.31
VAR_064001
Natural variant431H → R in ND. Ref.34
VAR_064002
Natural variant441Y → C in ND. Ref.13 Ref.31
VAR_005482
Natural variant451V → E in ND. Ref.37
VAR_064003
Natural variant451V → M in ND. Ref.31
VAR_064004
Natural variant541K → N in EVR2. Ref.39
VAR_064005
Natural variant551C → R in ND. Ref.40
VAR_064006
Natural variant581K → N in ND and EVR2. Ref.10 Ref.26
VAR_005483
Natural variant601V → E in ND; reduction of protein amount in the extracellular matrix. Ref.7 Ref.13
VAR_005484
Natural variant611L → F in ND. Ref.14 Ref.27
VAR_005485
Natural variant611L → I in EVR2. Ref.38
VAR_064007
Natural variant611L → P in ND. Ref.18
VAR_005486
Natural variant631A → D in ND. Ref.18
VAR_005487
Natural variant651C → W in ND. Ref.18
VAR_005490
Natural variant651C → Y in ND. Ref.20 Ref.38
VAR_005488
Natural variant671G → E in ND. Ref.40
VAR_064008
Natural variant671G → R in ND. Ref.40
VAR_064009
Natural variant691C → S in ND. Ref.15
VAR_005489
Natural variant741R → C in ND. Ref.14 Ref.23 Ref.35
VAR_005491
Natural variant751S → C in ND. Ref.14
VAR_005492
Natural variant751S → P in ND. Ref.30
VAR_016049
Natural variant891F → L in ND. Ref.40
VAR_064010
Natural variant901R → C in ND. Ref.31
VAR_064011
Natural variant901R → P in ND. Ref.14
VAR_005494
Natural variant921S → P in ND. Ref.40
VAR_064012
Natural variant94 – 963HCC → QCGL in ND.
VAR_005495
Natural variant951C → F in ND. Ref.32
VAR_064013
Natural variant951C → R in ND. Ref.17
VAR_064014
Natural variant961C → W in ND. Ref.29
VAR_009275
Natural variant961C → Y in ND. Ref.13 Ref.14 Ref.28
VAR_005496
Natural variant971R → P in ND. Ref.39
VAR_064015
Natural variant981P → L in ND. Ref.40
VAR_064016
Natural variant1011S → F in ND. Ref.25
VAR_005497
Natural variant1031L → V in EVR2. Ref.34
VAR_064017
Natural variant1041K → N in ND. Ref.36
VAR_064018
Natural variant1041K → Q in ND. Ref.19
VAR_005498
Natural variant1051A → T in ND. Ref.24
VAR_016050
Natural variant1081L → P in retinopathy of prematurity. Ref.26
VAR_064019
Natural variant1101C → G in ND. Ref.24
VAR_016051
Natural variant1101C → R in ND. Ref.23
VAR_064020
Natural variant1121G → E in ND. Ref.35
VAR_064021
Natural variant1151R → L in EVR2. Ref.39
VAR_064022
Natural variant1181A → D in ND. Ref.28
VAR_064023
Natural variant1201Y → C in EVR2. Ref.26
VAR_005499
Natural variant121 – 1233Missing in ND.
VAR_005503
Natural variant1211R → G in EVR2.
VAR_005500
Natural variant1211R → L in EVR2. Ref.22
VAR_064024
Natural variant1211R → Q in EVR2 and ND; reduced amount of protein in the extracellular matrix. Ref.7 Ref.10 Ref.19 Ref.33
VAR_005501
Natural variant1211R → W in ND and EVR2. Ref.19 Ref.38
VAR_005502
Natural variant1231I → N in ND. Ref.18
VAR_005504
Natural variant1241L → F in EVR2. Ref.16
Corresponds to variant rs28933684 [ dbSNP | Ensembl ].
VAR_005505
Natural variant1261C → S in ND. Ref.21
VAR_064025
Natural variant1281C → R in ND. Ref.31
VAR_064026

Experimental info

Mutagenesis951C → A: Impairs oligomerization. Ref.7

Secondary structure

................... 133
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q00604 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: D219E8B7F957286A

FASTA13315,044
        10         20         30         40         50         60 
MRKHVLAASF SMLSLLVIMG DTDSKTDSSF IMDSDPRRCM RHHYVDSISH PLYKCSSKMV 

        70         80         90        100        110        120 
LLARCEGHCS QASRSEPLVS FSTVLKQPFR SSCHCCRPQT SKLKALRLRC SGGMRLTATY 

       130 
RYILSCHCEE CNS 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of a candidate gene for Norrie disease by positional cloning."
Berger W., Meindl A., van de Pol T.J.R., Cremers F.P.M., Ropers H.-H., Doerner C., Monaco A., Bergen A.A.B., Lebo R., Warburg M., Zergollern L., Lorenz B., Gal A., Bleeker-Wagemakers E.M., Meitinger T.
Nat. Genet. 1:199-203(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Retina.
[2]Erratum
Berger W., Meindl A., van de Pol T.J.R., Cremers F.P.M., Ropers H.-H., Doerner C., Monaco A., Bergen A.A.B., Lebo R., Warburg M., Zergollern L., Lorenz B., Gal A., Bleeker-Wagemakers E.M., Meitinger T.
Nat. Genet. 2:84-84(1992) [PubMed] [Europe PMC] [Abstract]
[3]"Isolation and characterization of a candidate gene for Norrie disease."
Chen Z.-Y., Hendriks R.W., Jobling M.A., Powell J.F., Breakfield X.O., Sims K.B., Craig I.W.
Nat. Genet. 1:204-208(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal retina.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[5]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Norrie disease protein (norrin) forms disulfide-linked oligomers associated with the extracellular matrix."
Perez-Vilar J., Hill R.L.
J. Biol. Chem. 272:33410-33415(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, OLIGOMERIZATION, MUTAGENESIS OF CYS-95, CHARACTERIZATION OF VARIANTS ND GLU-60 AND GLN-121.
[8]"Localization of the Norrie disease gene mRNA by in situ hybridization."
Hartzer M.K., Cheng M., Liu X., Shastry B.S.
Brain Res. Bull. 49:355-358(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure."
Meitinger T., Meindl A., Bork P., Rost B., Sander C., Haasemann M., Murken J.
Nat. Genet. 5:376-380(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[10]"Identification of two new missense mutations (K58N and R121Q) in the Norrie disease (ND) gene in two Spanish families."
Fuentes J.J., Volpini V., Fernandez-Toral F., Coto E., Estivill X.
Hum. Mol. Genet. 2:1953-1955(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND ASN-58 AND GLN-121.
[11]"A missense point mutation (Leu13Arg) of the Norrie disease gene in a large Cuban kindred with Norrie disease."
Fuchs S., Xu S.Y., Caballero M., Salcedo M., Lo A.L., Wedemann H., Gal A.
Hum. Mol. Genet. 3:655-656(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND ARG-13.
[12]"Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene."
Joos K.M., Kimura A.E., Vandenburgh K., Bartley J.A., Stone E.M.
Arch. Ophthalmol. 112:1574-1579(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND ARG-39.
[13]"Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins."
Meindl A., Berger W., Meitinger T., van de Pol D., Achatz H., Dorner C., Haasemann M., Hellebrand H., Gal A., Cremers F.P.M., Ropers H.-H.
Nat. Genet. 2:139-143(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND CYS-44; GLU-60 AND TYR-96.
[14]"Mutations in the candidate gene for Norrie disease."
Berger W., van de Pol D., Warburg M., Gal A., Bleeker-Wagemakers L., de Silva H., Meindl A., Meitinger T., Cremers F.P.M., Ropers H.-H.
Hum. Mol. Genet. 1:461-465(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND PHE-61; CYS-74; CYS-75; PRO-90 AND TYR-96.
[15]"Characterization of a mutation within the NDP gene in a family with a manifesting female carrier."
Chen Z.-Y., Battinelli E.M., Woodruff G., Young I., Breakefield X.O., Craig I.W.
Hum. Mol. Genet. 2:1727-1729(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND SER-69.
[16]"A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy."
Chen Z.-Y., Battinelli E.M., Fielder A., Bundey S., Sims K., Breakefield X.O., Craig I.W.
Nat. Genet. 5:180-183(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EVR2 PHE-124.
[17]"Mutations in the Norrie disease gene: a new mutation in a Japanese family."
Isashiki Y., Ohba N., Yanagita T., Hokita N., Hotta Y., Hayakawa M., Fujiki K., Tanabe U.
Br. J. Ophthalmol. 79:703-704(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND ARG-95.
[18]"Mutations in the Norrie disease gene."
Schuback D.E., Chen Z.Y., Craig I.W., Breakefield X.O., Sims K.B.
Hum. Mutat. 5:285-292(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND PRO-61; ASP-63; TRP-65; ASN-123; 94-GLN--LEU-96 AND 121-ARG--ILE-123 DEL.
[19]"Missense mutations in the NDP gene in patients with a less severe course of Norrie disease."
Meindl A., Lorenz B., Achatz H., Hellebrand H., Schmitz-Valckenberg P., Meitinger T.
Hum. Mol. Genet. 4:489-490(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND GLN-104; TRP-121 AND GLN-121.
[20]"A novel mutation in the Norrie disease gene predicted to disrupt the cystine knot growth factor motif."
Strasberg P., Liede H.A., Stein T., Warren I., Sutherland J., Ray P.N.
Hum. Mol. Genet. 4:2179-2180(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND TYR-65.
[21]"Norrie-Warburg syndrome: two novel mutations in patients with classical clinical phenotype."
Gal A., Veske A., Jojart G., Grammatico B., Huber B., Gu S., del Porto G., Senyi K.
Acta Ophthalmol. Scand. Suppl. 219:13-16(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND SER-126.
[22]"X-linked exudative vitreoretinopathy caused by an arginine to leucine substitution (R121L) in the Norrie disease protein."
Johnson K., Mintz-Hittner H.A., Conley Y.P., Ferrell R.E.
Clin. Genet. 50:113-115(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EVR2 LEU-121.
[23]"Three novel and two recurrent mutations of the Norrie disease gene in patients with Norrie syndrome."
Fuchs S., van de Pol D., Beudt U., Kellner U., Meire F., Berger W., Gal A.
Hum. Mutat. 8:85-88(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND CYS-74 AND ARG-110.
[24]"Two new missense mutations (A105T and C110G) in the norrin gene in two Italian families with Norrie disease and familial exudative vitreoretinopathy."
Torrente I., Mangino M., Gennarelli M., Novelli G., Giannotti A., Vadala P., Dallapiccola B.
Am. J. Med. Genet. 72:242-244(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND THR-105 AND GLY-110.
[25]"Two new mutations in exon 3 of the NDP gene: S73X and S101F associated with severe and less severe ocular phenotype, respectively."
Walker J.L., Dixon J., Fenton C.R., Hungerford J., Lynch S.A., Stenhouses S.A.R., Christian A., Craig I.W.
Hum. Mutat. 9:53-56(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND PHE-101.
[26]"Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy."
Shastry B.S., Hejtmancik J.F., Trese M.T.
Hum. Mutat. 9:396-401(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR2 LYS-41; ARG-42; ASN-58 AND CYS-120, VARIANT RETINOPATHY OF PREMATURITY PRO-108.
[27]"Norrie disease gene mutation in a large Costa Rican kindred with a novel phenotype including venous insufficiency."
Rehm H.L., Gutierrez-Espeleta G.A., Garcia R., Jimenez G., Khetarpal U., Priest J.M., Sims K.B., Keats B.J.B., Morton C.C.
Hum. Mutat. 9:402-408(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND PHE-61.
[28]"Norrie disease and exudative vitreoretinopathy in families with affected female carriers."
Shastry B.S., Hiraoka M., Trese D.C., Trese M.T.
Eur. J. Ophthalmol. 9:238-242(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND TYR-96 AND ASP-118.
[29]"Coats' disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis."
Black G.C.M., Perveen R., Bonshek R., Cahill M., Clayton-Smith J., Lloyd I.C., McLeod D.
Hum. Mol. Genet. 8:2031-2035(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND TRP-96.
[30]"Two Thai families with Norrie disease (ND): association of two novel missense mutations with severe ND phenotype, seizures, and a manifesting carrier."
Yamada K., Limprasert P., Ratanasukon M., Tengtrisorn S., Yingchareonpukdee J., Vasiknanonte P., Kitaoka T., Ghadami M., Niikawa N., Kishino T.
Am. J. Med. Genet. 100:52-55(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND PRO-16 AND PRO-75.
[31]"NDP gene mutations in 14 French families with Norrie disease."
Royer G., Hanein S., Raclin V., Gigarel N., Rozet J.-M., Munnich A., Steffann J., Dufier J.-L., Kaplan J., Bonnefont J.-P.
Hum. Mutat. 22:499-499(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND CYS-38; GLN-43; CYS-44; MET-45; CYS-90 AND ARG-128.
[32]"A novel missense Norrie disease mutation associated with a severe ocular phenotype."
Khan A.O., Shamsi F.A., Al-Saif A., Kambouris M.
J. Pediatr. Ophthalmol. Strabismus 41:361-363(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND PHE-95.
[33]"Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR."
Riveiro-Alvarez R., Trujillo-Tiebas M.J., Gimenez-Pardo A., Garcia-Hoyos M., Cantalapiedra D., Lorda-Sanchez I., Rodriguez de Alba M., Ramos C., Ayuso C.
Mol. Vis. 11:705-712(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR2 CYS-38 AND GLN-121.
[34]"Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity."
Dickinson J.L., Sale M.M., Passmore A., FitzGerald L.M., Wheatley C.M., Burdon K.P., Craig J.E., Tengtrisorn S., Carden S.M., Maclean H., Mackey D.A.
Clin. Exp. Ophthalmol. 34:682-688(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EVR2 VAL-103, VARIANT ND ARG-43.
[35]"Phenotypic heterogeneity associated with a novel mutation (Gly112Glu) in the Norrie disease protein."
Allen R.C., Russell S.R., Streb L.M., Alsheikheh A., Stone E.M.
Eye 20:234-241(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND CYS-74 AND GLU-112.
[36]"Gene symbol: NDP. Disease: Norrie disease."
Riveiro-Alvarez R., Trujillo M.J., Gimenez A., Cantalapiedra D., Vallespin E., Villaverde C., Ayuso C.
Hum. Genet. 119:675-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND ASN-104.
[37]"A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms."
Lev D., Weigl Y., Hasan M., Gak E., Davidovich M., Vinkler C., Leshinsky-Silver E., Lerman-Sagie T., Watemberg N.
Am. J. Med. Genet. A 143:921-924(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ND GLU-45.
[38]"Retinal phenotype-genotype correlation of pediatric patients expressing mutations in the Norrie disease gene."
Wu W.-C., Drenser K., Trese M., Capone A. Jr., Dailey W.
Arch. Ophthalmol. 125:225-230(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR2 ARG-42; ILE-61 AND TRP-121, VARIANTS ND ARG-39 AND TYR-65, VARIANT PERSISTENT FETAL VASCULATURE SYNDROME SER-41.
[39]"Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy."
Kondo H., Qin M., Kusaka S., Tahira T., Hasebe H., Hayashi H., Uchio E., Hayashi K.
Invest. Ophthalmol. Vis. Sci. 48:1276-1282(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR2 LYS-18; ASN-54 AND LEU-115, VARIANT ND PRO-97.
[40]"Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP."
Nikopoulos K., Venselaar H., Collin R.W.J., Riveiro-Alvarez R., Boonstra F.N., Hooymans J.M., Mukhopadhyay A., Shears D., van Bers M., de Wijs I.J., van Essen A.J., Sijmons R.H., Tilanus M.A.D., van Nouhuys C.E., Ayuso C., Hoefsloot L.H., Cremers F.P.M.
Hum. Mutat. 31:656-666(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ND ARG-55; ARG-67; GLU-67; LEU-89; PRO-92 AND LEU-98.
+Additional computationally mapped references.

Web resources

Mutations of the NDP gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X65724 mRNA. Translation: CAA46639.1.
X65882 mRNA. Translation: CAA46713.1.
AL034370 Genomic DNA. Translation: CAA22268.1.
AK313409 mRNA. Translation: BAG36203.1.
BC029901 mRNA. Translation: AAH29901.1.
CCDSCCDS14262.1.
PIRA57005.
RefSeqNP_000257.1. NM_000266.3.
UniGeneHs.522615.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4MY2X-ray2.40A30-133[»]
ProteinModelPortalQ00604.
SMRQ00604. Positions 1-133.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110773. 6 interactions.
IntActQ00604. 4 interactions.
STRING9606.ENSP00000367301.

Polymorphism databases

DMDM548342.

Proteomic databases

PaxDbQ00604.
PRIDEQ00604.

Protocols and materials databases

DNASU4693.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378062; ENSP00000367301; ENSG00000124479.
GeneID4693.
KEGGhsa:4693.
UCSCuc004dga.3. human.

Organism-specific databases

CTD4693.
GeneCardsGC0XM043808.
GeneReviewsNDP.
HGNCHGNC:7678. NDP.
HPAHPA003095.
MIM300658. gene.
305390. phenotype.
310600. phenotype.
neXtProtNX_Q00604.
Orphanet190. Coats disease.
891. Familial exudative vitreoretinopathy.
649. Norrie disease.
91495. Persistent hyperplastic primary vitreous.
90050. Retinopathy of prematurity.
PharmGKBPA31481.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG270934.
HOGENOMHOG000030892.
HOVERGENHBG004945.
InParanoidQ00604.
OMAKQPFRST.
OrthoDBEOG7W41DV.
PhylomeDBQ00604.

Gene expression databases

BgeeQ00604.
CleanExHS_NDP.
GenevestigatorQ00604.

Family and domain databases

InterProIPR006207. Cys_knot_C.
IPR006208. Glyco_hormone_CN.
IPR003064. Norrie_dis.
[Graphical view]
PfamPF00007. Cys_knot. 1 hit.
[Graphical view]
PRINTSPR01304. NORRIEDSEASE.
SMARTSM00041. CT. 1 hit.
[Graphical view]
PROSITEPS01185. CTCK_1. 1 hit.
PS01225. CTCK_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNorrin.
GenomeRNAi4693.
NextBio18098.
PROQ00604.
SOURCESearch...

Entry information

Entry nameNDP_HUMAN
AccessionPrimary (citable) accession number: Q00604
Secondary accession number(s): B2R8K6, Q5JYH5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM