NPHP3
MIM.608002 3q22
Nephrocystin-3 directly interacts with inversin (IVS) and can inhibit like inversin canonical Wnt signaling.
Pathology
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
Ciliopathies
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#)
References
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#