Cystic kidney disease

Gene: TULP3

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 5:25 p.m. | Last Modified: 10 Oct 2023, 5:25 p.m.

Panel Version: 4.17

Comment on list classification: As reviewed by John Sayer, there is sufficient evidence (8 unrelated cases and supporting functional evidence from animal models) for this gene to be promoted to GREEN rating at the next GMS update.

Created: 22 May 2023, 6:38 p.m. | Last Modified: 23 May 2023, 8:48 a.m.

Panel Version: 4.4

PMID:35397207 reported individuals from eight unrelated families with biallelic variants in TULP3 gene, out of which individuals from six families had kidney abnormalities including presentation of kidney cysts in at least an individual from five families. In addition, experiments in TULP3 knockout zebrafish models recapitulated the phenotypes observed in patients including the kidney cysts.

PMID:36276950 reported two sisters with fibrocystic renal and hepatic disease harboring a homozygous missense mutation in TULP3 (p.Arg382Trp). In addition, experiments with inner medullary collecting duct-3 cells expressing the TULP3 R382W patient variant showed that this variant had a severely reduced ability to localise membrane-associated proteins to the cilium, consistent with a loss of TULP3 function.

PMID:36460032 reported two cases with biallelic variants in TULP3 (patient A: homozygous; patient B: compound heterozygous) and both had cystic kidney disease.

Functional studies from mouse models also showed that knockout mice developed cystic kidney disease (PMIDs: 30799239 & 30799240).

This gene has been associated with relevant phenotypes in OMIM (MIM #619902), but not in Gene2Phenotype.

Created: 22 May 2023, 6:34 p.m. | Last Modified: 22 May 2023, 6:47 p.m.

Panel Version: 4.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hepatorenocardiac degenerative fibrosis, OMIM:619902

Publications

• 30799239
• 30799240
• 35397207
• 36276950
• 36460032

Green List (high evidence)

TULP3 is a novel human cilipathy gene (OMIM 604730)
Hepatorenocardiac degenerative fibrosis is OMIM pehnotype
Cystic kidney disease is a typical feature
Sources: Expert list

Created: 7 Apr 2023, 4:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cystic kidney disease; ductal plate malformation; congentital hepatic fibrosis; cardiomyopathy

Publications

• 36460032
• 36276950
• 35397207