Respiratory ciliopathies including non-CF bronchiectasis

Gene: CFAP54

Green List (high evidence)

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

Created: 11 Dec 2025, 4:33 p.m. | Last Modified: 11 Dec 2025, 4:33 p.m.

Panel Version: 4.50

Green List (high evidence)

The ClinGen Motile Ciliopathy expert panel has classified the association of autosomal recessive CFAP54 variants to ciliary dyskinesia, primary, 54 (MONDO:0100607) as 'Strong'. More information can be found in https://search.clinicalgenome.org/

Created: 17 Jul 2025, noon | Last Modified: 17 Jul 2025, noon

Panel Version: 4.41

Comment on list classification: As reviewed by Steven Cowman and associated with relevant phenotypes in OMIM (MIM #621125), there is sufficient evidence available (five unrelated families and mouse model) for the promotion of this gene to green rating on the next GMS update.

Created: 1 Apr 2025, 7:24 p.m. | Last Modified: 1 Apr 2025, 7:24 p.m.

Panel Version: 3.29

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 54, OMIM:621125

Publications

• 37725231
• 39362668

Green List (high evidence)

There are reports of pathogenic variants in this gene associated with bronchiectasis in six patients, five of whom are unrelated.

One report (PMID 39362668) describes four unrelated patients aged between 2 and 25 years old, three of whom were compound heterozygous and one homozygous for pathogenic variants in CFAP54. All reported chronic respiratory symptoms and all three patients for whom data was available had bronchiectasis. Two patients reported neonatal chest symptoms, one did not and data was missing for the other patient. No data were available on fertility status. In keeping with other C1d mutations they all had situs solitus and normal EM and HSVMA in those where data were available, but studies of in vitro ciliary transport performed in two subjects found that this was impaired in both.

A previous report (PMID 37725231) found two siblings (one male, one female) who were compound heterozygous for two likely pathogenic variants in CFAP54, both of whom had proven bronchiectasis. The sister was reported to have newborn pneumonia and rhinitis and sinusitis of childhood onset. In the brother, nasal NO was above the diagnostic cut-off and ciliary beat frequency was normal, but semen analysis found morphological abnormalities including short or absent flagella. A further unrelated male was found to be compound heterozygous for two other missense variants, he had confirmed bronchiectasis and childhood pneumonia followed by a chronic productive cough. He was reported have two children although semen analysis was not performed.

Created: 19 Mar 2025, 4:30 p.m. | Last Modified: 19 Mar 2025, 4:30 p.m.

Panel Version: 3.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia; bronchiectasis

Publications

• 39362668
• 37725231

Red List (low evidence)

Submitted on behalf of NHS GMS "We have been sequencing this gene for the past 2-3 years and have not yet found a clearly pathogenic variant. A number of truncating variants were identified in CFAP54 in the 100K project, but in patients with diagnoses other than PCD and loss of function does not appear to be a disease mechanism for this gene."

Created: 8 Mar 2022, 11:15 a.m. | Last Modified: 8 Mar 2022, 11:15 a.m.

Panel Version: 1.55

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

Created: 8 Mar 2022, 11:15 a.m. | Last Modified: 8 Mar 2022, 11:15 a.m.

Panel Version: 1.55

This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. There are no reports of this gene being associated with a phenotype in humans. There are mouse models only. Therefore, this gene should be demoted to Red at the next review.

Created: 2 Dec 2020, 11:47 a.m. | Last Modified: 2 Dec 2020, 11:47 a.m.

Panel Version: 1.24

Red List (low evidence)

Mouse model only, cannot find reports in humans.

Created: 25 May 2020, 6:39 a.m. | Last Modified: 25 May 2020, 6:39 a.m.

Panel Version: 1.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 26224312

I don't know

Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: CFAP54; Suggested initial gene rating: Amber; Evidence for inclusion: Causes classical PCD in mouse model.; Evidence for exclusion: Not reported yet in humans.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 5 Dec 2018, 1:54 p.m.