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Home > A. Molecular pathology > NPHP3


MIM.608002 3q22

Monday 27 September 2004

Nephrocystin-3 directly interacts with inversin (IVS) and can inhibit like inversin canonical Wnt signaling.


- germline mutations in adolescent nephronophthisis with tapetoretinal degeneration and hepatic fibrosis (NPHP3 locus at 3q21-q22 (12872122).

NPHP3 mutations can cause a broad clinical spectrum of early embryonic patterning defects comprising (18371931):

- situs inversus
- polydactyly
- central nervous system malformations
- structural heart defects
- preauricular fistulas
- congenital anomalies of the kidney and urinary tract (CAKUT)
- embryonic lethality
- Meckel-Gruber-like syndrome (Meckel syndrome like)
- situs inversus
- renal-hepatic-pancreatic dysplasia


Many genetic diseases have been linked to the dysfunction of primary cilia, which occur nearly ubiquitously in the body and act as solitary cellular mechanosensory organelles.

The list of clinical manifestations and affected tissues in cilia-related disorders (ciliopathies) such as nephronophthisis is broad and has been attributed to the wide expression pattern of ciliary proteins.

Animal models

- In mice, pcy mutation generates a hypomorphic Nphp3 allele that is responsible for the cystic kidney disease phenotype, whereas complete loss of Nphp3 function results in situs inversus, congenital heart defects, and embryonic lethality in mice. (18371931)

- Nephrocystin-3 deficiency leads in Xenopus laevis to typical planar cell polarity defects (PCP defects), suggesting a role in the control of canonical and noncanonical (planar cell polarity) Wnt signaling pathway. (18371931)


- Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Bergmann C, Fliegauf M, Brüchle NO, Frank V, Olbrich H, Kirschner J, Schermer B, Schmedding I, Kispert A, Kränzlin B, Nürnberg G, Becker C, Grimm T, Girschick G, Lynch SA, Kelehan P, Senderek J, Neuhaus TJ, Stallmach T, Zentgraf H, Nürnberg P, Gretz N, Lo C, Lienkamp S, Schäfer T, Walz G, Benzing T, Zerres K, Omran H. Am J Hum Genet. 2008 Apr;82(4):959-70. PMID: 18371931

- Olbrich H, Fliegauf M, Hoefele J, Kispert A, Otto E, Volz A, Wolf MT, Sasmaz G, Trauer U, Reinhardt R, Sudbrak R, Antignac C, Gretz N, Walz G, Schermer B, Benzing T, Hildebrandt F, Omran H. Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Nat Genet. 2003 Aug;34(4):455-9. PMID: 12872122