Respiratory ciliopathies including non-CF bronchiectasis

Gene: CFAP74

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

Note that the ClinGen Motile Ciliopathy expert panel have classified this association as Limited due to a lack of immunofluorescence data on CFAP74 localisation in multiciliated cells and lack of patient cell evidence confirming a central complex protein defect - https://search.clinicalgenome.org/CCID:004429

Tagging for review as the GMS expert group may still want to include this gene on the panel based on the four unrelated cases reported in literature.

Created: 20 Jun 2025, 8:21 a.m. | Last Modified: 20 Jun 2025, 8:21 a.m.

Panel Version: 4.4

Green List (high evidence)

Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIM #620197) and the OMIM record was last accessed on 18 December 2025.

Created: 18 Dec 2025, 11:06 p.m. | Last Modified: 18 Dec 2025, 11:06 p.m.

Panel Version: 4.51

The ClinGen Motile Ciliopathy expert panel has updated the classification for the association of CFAP74 gene to ciliary dyskinesia, primary, 49, without situs inversus (MONDO:0859353) from 'Limited' to 'Moderate' on 18/06/2025.

The reason for classification change is summarised in ClinGen (https://search.clinicalgenome.org/CCID:004429) as follows:
"Recurated and changed classification from Limited to Moderate. Additional proband from a ClinVar submission, and additional immunofluorescence data from patients previously reported."

Created: 17 Jul 2025, 9:33 p.m. | Last Modified: 17 Jul 2025, 9:33 p.m.

Panel Version: 4.44

Comment on list classification: As reviewed by Steven Cowman and associated with relevant phenotypes in OMIM (MIM #620197), there is sufficient evidence available (four unrelated families in total) for the promotion of this gene to green rating on the next GMS update.

Created: 31 Mar 2025, 6:53 p.m. | Last Modified: 31 Mar 2025, 6:53 p.m.

Panel Version: 3.28

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 49, without situs inversus, OMIM:620197

Publications

• 32555313
• 36047773
• 39362668

Green List (high evidence)

Associated with PCD phenotype in OMIM (#620197) based on two reports.

Sha et al. (PMID 32555313) reported two unrelated patients who were both compound heterozygotes for missense mutations in this gene and had a typical PCD phenotype of a chronic productive cough, bronchiectasis confirmed on CT scan, chronic sinusitis and male infertility associated with multiple morphological abnormalities of the sperm flagella. Immunofluorescence found absence of CFAP74 protein in sperm from affected cases.

Biebach et al. (PMID 36047773) report three individuals (two male one female) from two non-consanguineous families who were compound heterozygotes for missense mutations in this gene and all reported recurrent respiratory tract infections with childhood onset. Immunoblot analysis revealed absent CFAP74 protein in axonemal extracts from two affected subjects. The presented radiology shows bronchiectasis in one subject and chronic sinusitis in another. One male was reported to have oligoasthenospermia (the fertility status of the other male was not reported). All had situs solitus. Nasal NO values were normal. TEM in two individuals showed normal ciliary ultrastructure, but a reduced ciliary beat frequency and beating pattern were seen on video microscopy and ciliary clearance capacity was found to be reduced. Further clinical information on these individuals was subsequently given by Wohlgemuth et al. (PMID 39362668) who confirms that bronchiectasis was found in the two patients for whom this information is available.

Created: 28 Feb 2025, 4:54 p.m. | Last Modified: 28 Feb 2025, 4:54 p.m.

Panel Version: 3.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia

Publications

• 32555313
• 36047773
• 39362668

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. Based on the available evidence there is not enough evidence to support a gene-disease association. This gene has been given an Amber rating.

Created: 1 Dec 2020, 4:09 p.m. | Last Modified: 1 Dec 2020, 4:09 p.m.

Panel Version: 1.14

I don't know

Two unrelated individuals with compound het missense variants reported.
Sources: Literature

Created: 6 Jul 2020, 8:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia; infertility

Publications

• 32555313