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NDP gene
URL of this page: https://medlineplus.gov/genetics/gene/ndp/

NDP gene

norrin cystine knot growth factor NDP

Normal Function

The NDP gene provides instructions for making a protein called norrin. Norrin participates in chemical signaling pathways that affect the way cells and tissues develop. Studies suggest that norrin may play a role in Wnt signaling, which is important for cell division (proliferation), attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities.

Norrin is one of many proteins, or ligands, that can attach (bind) to other proteins called frizzled receptors.  These receptors are embedded in the outer membranes of cells. Norrin binds with the receptor frizzled-4 (produced from the FZD4 gene). The two proteins fit together like a key in a lock. When a ligand binds to a frizzled receptor, it initiates a multi-step process that regulates the activity of certain genes.

The norrin protein and frizzled-4 participate in developmental processes that are believed to be crucial for normal development of the eye and other body systems. In particular, norrin seems to play critical roles in the specialization of cells in the retina (the light-sensitive tissue that lines the back of the eye) and the formation of blood vessels in the retina and in the inner ear.

Health Conditions Related to Genetic Changes

Familial exudative vitreoretinopathy

Several NDP gene variants (also called mutations) have been found to cause the eye disorder familial exudative vitreoretinopathy. This disorder affects the retina and can cause vision loss that worsens over time. These variants change single protein building blocks (amino acids) in the norrin protein, altering the normal folding of norrin or preventing it from binding to frizzled-4. The defective norrin disrupts chemical signaling in the developing eye, which interferes with the formation of blood vessels at the edges of the retina. The resulting abnormal blood supply to this tissue leads to retinal damage and vision loss in some people with familial exudative vitreoretinopathy.

More About This Health Condition

Norrie disease

Several variants in the NDP gene have been identified in people with Norrie disease. Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. The NDP gene variants that cause this condition affect the ability of the norrin protein to bind with frizzled-4, interfering with the specialization of retinal cells. As a result, immature retinal cells accumulate in the back of the eyes. The variants also affect the formation of the blood vessels that carry blood to the eye. Without these vessels. some of the tissues of the eye eventually break down.

Norrin is also expressed in other systems of the body, and the effects of the disorder can be widespread and include intellectual disabilities, seizures, behavioral problems, and delayed development. The specific abnormalities and their severity depend on the type and location of the NDP gene variant. Variants that delete portions of the NDP gene prevent the production of norrin and result in severe problems that affect many body systems in addition to the eyes. Variants that delete or change single amino acids usually result in less widespread effects.

More About This Health Condition

Other retinal dystrophies

NDP gene variants may cause other disorders that affect the retina. One of these disorders is called Coats disease. This disorder causes leakage of blood vessels in the retina and retinal detachment, a condition in which layers of the retina separate. This condition can result in vision loss. 

Persistent hyperplastic primary vitreous (PHPV) is another retinal disorder that may be caused by NDP gene variants. In PHPV, a remnant of a blood vessel found in the eye before birth remains as a fibrous white stalk between the back of the eye and the lens. Persistent hyperplastic primary vitreous can cause vision loss through retinal detachment, cloudiness of the lens (cataract), or increased pressure inside the eye (glaucoma) that can damage the optic nerve.

In addition, NDP gene variants may influence the course of a retinal disorder that affects some premature infants. Retinopathy of prematurity is a condition in which abnormal blood vessels appear in the retina and can cause retinal detachment. Babies with retinopathy of prematurity may experience improvement of the condition over time, but some NDP gene variants have been associated with a worsening of the condition.

Other Names for This Gene

  • ND
  • NDP_HUMAN
  • Norrie disease (pseudoglioma)
  • norrin

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Chen ZY, Hendriks RW, Jobling MA, Powell JF, Breakefield XO, Sims KB, Craig IW. Isolation and characterization of a candidate gene for Norrie disease. Nat Genet. 1992 Jun;1(3):204-8. doi: 10.1038/ng0692-204. Citation on PubMed
  • Clevers H. Wnt signaling: Ig-norrin the dogma. Curr Biol. 2004 Jun 8;14(11):R436-7. doi: 10.1016/j.cub.2004.05.039. Citation on PubMed
  • Dickinson JL, Sale MM, Passmore A, FitzGerald LM, Wheatley CM, Burdon KP, Craig JE, Tengtrisorn S, Carden SM, Maclean H, Mackey DA. Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity. Clin Exp Ophthalmol. 2006 Sep-Oct;34(7):682-8. doi: 10.1111/j.1442-9071.2006.01314.x. Citation on PubMed
  • Haider MZ, Devarajan LV, Al-Essa M, Kumar H. A C597-->A polymorphism in the Norrie disease gene is associated with advanced retinopathy of prematurity in premature Kuwaiti infants. J Biomed Sci. 2002 Jul-Aug;9(4):365-70. doi: 10.1007/BF02256593. Citation on PubMed
  • Hiraoka M, Berinstein DM, Trese MT, Shastry BS. Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity. J Hum Genet. 2001;46(4):178-81. doi: 10.1007/s100380170085. Citation on PubMed
  • Kondo H, Qin M, Kusaka S, Tahira T, Hasebe H, Hayashi H, Uchio E, Hayashi K. Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1276-82. doi: 10.1167/iovs.06-1042. Citation on PubMed
  • Royer G, Hanein S, Raclin V, Gigarel N, Rozet JM, Munnich A, Steffann J, Dufier JL, Kaplan J, Bonnefont JP. NDP gene mutations in 14 French families with Norrie disease. Hum Mutat. 2003 Dec;22(6):499. doi: 10.1002/humu.9204. Citation on PubMed
  • Scruggs BA, Reding MQ, Schimmenti LA. NDP-Related Retinopathies. 1999 Jul 30 [updated 2023 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1331/ Citation on PubMed
  • Shastry BS. Genetic susceptibility to advanced retinopathy of prematurity (ROP). J Biomed Sci. 2010 Aug 25;17(1):69. doi: 10.1186/1423-0127-17-69. Citation on PubMed or Free article on PubMed Central
  • Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004 Mar 19;116(6):883-95. doi: 10.1016/s0092-8674(04)00216-8. Citation on PubMed

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