The NPHP3 gene encodes for Nephrocystin 3, a protein involved in the negative regulation of canonical Wnt signaling pathway.  The protein plays an important role in development and is involved in cilium assembly, kidney morphogenesis, determination of left/right symmetry, regulation of planar cell polarity (i.e. in neural tube closure) and maintenance of animal organ identity.

The gene has been implicated in three allelic overlapping disorders: Meckel syndrome 7 (MKS7), Nephronophthisis 3 (NPHP3) and Renal-Hepatic-Pancreatic Dysplasia 1 (RHPD1).  MKS7 is lethal ciliopathy characterized by Dandy-Walker malformation, cystic kidney disease and hepatic abnormalities.  NPHP3 is a milder autosomal recessive cystic kidney disease resulting in renal failure and hepatic fibrosis.  RHPD1 is an often fatal disorder that results in abnormalities of the kidneys, liver, pancreas, heart, lungs, spleen and central nervous system. 

The NPHP3 gene is located on the long arm of chromosome 3.  It spans a length of 41.8 kb of DNA and its coding sequence is spread across 27 exons.  The protein encoded by this gene is made up of 1330 amino acids and has a molecular mass of 150 kDa.  Multiple isoforms of the NPHP3 protein exist due to alternative splicing.  While the gene is widely expressed in the heart, placenta, liver, skeletal muscle, kidney and pancreas, it is overexpressed in the nasal epithelium and cerebrospinal fluid.  Mutations in the gene associated with MKS7, Nephronophthisis 3 and RHPD1 include homozygous and compound heterozygous deletions, missense and nonsense mutations.