Renal ciliopathies

Gene: IFT140

Comment on phenotypes: OMIM phenotype accessed 25th Feb 2026.

Created: 25 Feb 2026, 12:11 p.m. | Last Modified: 25 Feb 2026, 12:11 p.m.

Panel Version: 4.7

The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 11:22 a.m. | Last Modified: 8 Mar 2022, 11:22 a.m.

Panel Version: 1.59

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 10:44 a.m. | Last Modified: 8 Mar 2022, 10:44 a.m.

Panel Version: 1.51

Comment on mode of inheritance: Leaving the mode of inheritance as biallelic for now, but with a recommendation that it should be updated to BOTH monoallelic and biallelic following GMS review.

Created: 14 Dec 2021, 11:57 a.m. | Last Modified: 14 Dec 2021, 11:57 a.m.

Panel Version: 1.45

As reported by John Sayer PMID: 34890546 (Senum et al 2021) reports 12 familial cases and 26 singletons with heterozygous variants in IFT140 and mild PKD with large cysts, limited kidney insufficiency, and few liver cysts. The mode of inheritance should therefore be updated to be BOTH monoallelic and biallelic on this panel, and a green rating following GMS review.

Created: 14 Dec 2021, 11:46 a.m. | Last Modified: 14 Dec 2021, 11:46 a.m.

Panel Version: 1.42

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Peter Harris identified monoallelic IFT140 loss-of-function (LoF) variants in 12 multiplex families and 26 singletons (1.9% of naive families). IFT140 is a core component of the intraflagellar transport-complex A, responsible for retrograde ciliary trafficking and ciliary entry of membrane proteins; bi-allelic IFT140 variants cause the syndromic ciliopathy, short-rib thoracic dysplasia (SRTD9). The distinctive monoallelic phenotype is mild PKD with large cysts, limited kidney insufficiency, and few liver cysts. Analyses of the cystic kidney disease probands of Genomics England 100K showed that 2.1% had IFT140 LoF variants.

Created: 11 Dec 2021, 10:27 a.m. | Last Modified: 11 Dec 2021, 10:27 a.m.

Panel Version: 1.42

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cystic kidney disease; cystic liver disease

Publications

• https://doi.org/10.1016/j.ajhg.2021.11.016

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.

Created: 19 Oct 2020, 2:29 p.m. | Last Modified: 19 Oct 2020, 2:29 p.m.

Panel Version: 1.29

Comment on list classification: Sufficient publications and external expert review an association of IFT140 variants and ciliopathic renal phenotype to rate IFT140 as Green.

Created: 30 Mar 2020, 1:39 p.m. | Last Modified: 30 Mar 2020, 1:39 p.m.

Panel Version: 1.10

Comment on list classification: Sufficient publications and external expert review an association of IFT140 variants and ciliopathic renal phenotype to rate IFT140 as Green.

Created: 30 Mar 2020, 1:39 p.m. | Last Modified: 30 Mar 2020, 1:39 p.m.

Panel Version: 1.10

Green List (high evidence)

Renal ciliopathy gene with phenotype of Mainzer-Saldino syndrome.

Nephronophthisis reported in multiple cases, with functional evidence (Patient-iPSC-Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype).
Sources: Expert Review

Created: 3 Jan 2020, 4:10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM #266920 (aka Mainzer-Saldino syndrome)

Publications

• PMID: 22503633, 23418020, 29706353