RGD Reference Report - Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.

General

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.
Authors:	Otto, Edgar A Schermer, Bernhard Obara, Tomoko O'Toole, John F Hiller, Karl S Mueller, Adelheid M Ruf, Rainer G Hoefele, Julia Beekmann, Frank Landau, Daniel Foreman, John W Goodship, Judith A Strachan, Tom Kispert, Andreas Wolf, Matthias T Gagnadoux, Marie F Nivet, Hubert Antignac, Corinne Walz, Gerd Drummond, Iain A Benzing, Thomas Hildebrandt, Friedhelm
Citation:	Otto EA, etal., Nat Genet. 2003 Aug;34(4):413-20. doi: 10.1038/ng1217.
RGD ID:	155791687
Pubmed:	PMID:12872123 (View Abstract at PubMed)
PMCID:	PMC3732175 (View Article at PubMed Central)
DOI:	DOI:10.1038/ng1217 (Journal Full-text)
Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
INVS	Human	nephronophthisis 2		IAGP		DNA:missense mutations more ...	RGD
Invs	Mouse	nephronophthisis 2		ISO	INVS (Homo sapiens)	DNA:missense mutations more ...	RGD
Invs	Rat	nephronophthisis 2		ISO	INVS (Homo sapiens)	DNA:missense mutations more ...	RGD

Objects Annotated

Genes (Rattus norvegicus)

Invs (inversin)

Genes (Mus musculus)

Invs (inversin)

Genes (Homo sapiens)

INVS (inversin)

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Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.