Cystic kidney disease

Gene: CFAP47

Red List (low evidence)

Comment on list classification: Based on conflicting and disputing evidence outlined in the ClinGen curation of evidence linking CFAP47 and X-linked polycystic kidney disease, the rating should be demoted to Red on this panel.

Created: 25 Sep 2026, 2:25 p.m. | Last Modified: 25 Sep 2026, 2:25 p.m.

Panel Version: 9.2

The association between CFAP47 and X-linked polycystic kidney disease was classified as Disputed on 02/10/2025 by the ClinGen Kidney Cystic and Ciliopathy Disorders Expert panel (see https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_da276c83-09e0-428f-a58e-6cd3bf517d00-2025-02-10T170000.000Z) The disputing evidence relates to PMID:39698362 and includes "non-specific genetically heterogenous phenotype, missense variant with no convincing functional data" for the 3 male patients with polycystic kidney disease. 2/3 variants are common in gnomAD v4, with homozygous and numerous hemizygous individuals reported. The curation summary states that "the gene may be associated with a susceptibility phenotype that could manifest with age-dependent incomplete penetrance."

There is also conflicting functional evidence: PMID: 36571501 describes a knockout 40-week-old mice model with "larger kidneys, cyst-like histological changes in the kidneys, including tubular cell vacuolation and dilatation, and they had significantly shorter cilia compared to wild types. However, another study published later reported that 10-week-old knockout mice showed no apparent histological kidney problems (PMID: 40473901)." - consistent with later onset?

Created: 25 Sep 2026, 2:21 p.m. | Last Modified: 25 Sep 2026, 2:30 p.m.

Panel Version: 9.2

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
polycystic kidney disease, MONDO:0020642

Publications

• 39698362

Green List (high evidence)

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

Created: 11 Mar 2026, 2:25 p.m. | Last Modified: 11 Mar 2026, 2:25 p.m.

Panel Version: 8.7

Comment on list classification: There is sufficient evidence available (three unrelated cases and functional work) for the promotion of this gene to green rating in the next GMS update.

Created: 23 Dec 2024, 7:21 p.m. | Last Modified: 23 Dec 2024, 7:21 p.m.

Panel Version: 7.10

PMID:39698362 reported the identification of three different rare missense variants in CFAP47 gene in three male patients with polycystic kidney disease. Some functional work is also available in support of the association.

This gene has not yet been associated with polycystic kidney disease phenotype either in OMIM or in Gene2Phenotype.

Created: 23 Dec 2024, 7:20 p.m. | Last Modified: 23 Dec 2024, 7:20 p.m.

Panel Version: 7.7

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
polycystic kidney disease, MONDO:0020642

Publications

• 39698362

Green List (high evidence)

Three cases & some functional work described in PMID: 38633811 (now published).
Sources: Literature

Created: 3 Dec 2024, 11:44 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
PKD

Publications

• PMID: 38633811

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments