Cystic kidney disease

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: 8.5

Green List (high evidence)

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

Created: 30 Jan 2023, 4:25 p.m. | Last Modified: 30 Jan 2023, 4:25 p.m.

Panel Version: 3.4

Green List (high evidence)

As previous reviewers, now strong evidence
PMID 34890546: Monoallelic variants described in 12 unrelated families with mild PKD associated with mild PKD with large cysts, limited kidney insufficiency, and few liver cysts.

Created: 13 Jun 2022, 8:49 a.m. | Last Modified: 13 Jun 2022, 8:49 a.m.

Panel Version: 2.45

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
cystic kidney disease; cystic liver disease

Publications

• 34890546

Comment on list classification: Promoting from grey to amber with a recommendation for GREEN rating following GMS review.

Created: 21 May 2022, 10:28 p.m. | Last Modified: 21 May 2022, 10:28 p.m.

Panel Version: 2.45

Comment on mode of inheritance: As reviewer notes there are several biallelic cases reported with a renal phenotype (e.g. PMID: 23418020 - 3 patients with renal cysts and biallelic IFT140 variants, PMID: 27874174 - 1 patient with renal cysts and biallelic IFT140 variants) aswell as the monallelic variants reported in PMID:34890546

Created: 21 May 2022, 10:25 p.m. | Last Modified: 21 May 2022, 10:25 p.m.

Panel Version: 2.42

Green List (high evidence)

PMID 34890546: Monoallelic variants described in 12 unrelated families with mild PKD associated with mild PKD with large cysts, limited kidney insufficiency, and few liver cysts.

Bilallelic variants associated with Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, where renal cysts are a feature, with early progressive renal disease.

Therefore both MOIs relevant to this panel.

Created: 3 Feb 2022, 9:02 a.m. | Last Modified: 3 Feb 2022, 9:02 a.m.

Panel Version: 2.31

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Cystic Kidney Disease, MONDO# 0002473, IFT140-related, dominant

Publications

• 22503633
• 23418020
• 34890546

Green List (high evidence)

This publication provides strong evidence that variants in this gene are a significant cause of polycystic kidney disease. Plausible mutations are identified in more than 3 unrelated families.

Created: 12 Jan 2022, 11:27 a.m. | Last Modified: 12 Jan 2022, 11:27 a.m.

Panel Version: 2.31

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autosomal dominant polycystic kidney disease

Publications

• 34890546

Green List (high evidence)

Very strong evidence of association of truncating IFT140 mutations and cystic kidney disease in cited paper, which includes 12 multiplex families and 26 singletons. In addition, hypothesis-free region-based variance testing (SKAT-O) independently identifying truncating variants in this gene in 100,000 Genomes Project (p=3.5e-17) and UK BioBank (p=4.5e-15) participants with cystic kidney disease (see https://genebass.org/gene/undefined/phenotype/icd_first_occurrence-132532-both_sexes--?resultIndex=gene-manhattan&resultLayout=full for UKBB analysis).
Sources: Literature, Research

Created: 11 Jan 2022, 1:06 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cystic kidney disease; chronic kidney disease

Publications

• 34890546