Respiratory ciliopathies including non-CF bronchiectasis

Gene: CFAP221

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)

Comment on phenotypes: This gene has been associated with relevant phenotypes in OMIM (MIM #279000) and the OMIM record was last accessed on 18 December 2025.

Created: 18 Dec 2025, 11:15 p.m. | Last Modified: 18 Dec 2025, 11:15 p.m.

Panel Version: 4.54

Comment on list classification: There is sufficient evidence available now for the promotion of this gene to green rating in the next GMS update.

Created: 7 Jul 2025, 8:38 a.m. | Last Modified: 7 Jul 2025, 8:38 a.m.

Panel Version: 4.17

The ClinGen Motile Ciliopathy expert panel has classified the association of CFAP221 gene to primary ciliary dyskinesia (MONDO:0016575) as 'Moderate'. More information can be found in https://search.clinicalgenome.org/CCID:004421.

There are additional cases reported with primary ciliary dyskinesia now.

PMID:38960684 - A 42-year-old male patient with bronchiectasis, sinusitis and a history of infertility treatment for obstructive azoospermia were identified with compound heterozygous deletion variants.

PMID:40250778 - A Polish male patient with PCD was identified with a novel homozygous protein-truncating variant in CFAP221 gene (p.Asp146His). The patient was reported with neonatal respiratory distress, admission to neonatal unit, congenital heart defect, chronic cough, otitis media, and sinusitis, glue ear and conductive hearing loss.

This gene has also been associated with relevant phenotypes in OMIM (MIM #279000).

Created: 4 Jul 2025, 1:52 p.m. | Last Modified: 17 Jul 2025, 2:01 p.m.

Panel Version: 4.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 55, OMIM:279000

Publications

• 31636325
• 38960684
• 39362668
• 40250778

I don't know

There is one report (PMID: 31636325) of three siblings all presenting with a PCD phenotype (neonatal respiratory distress, productive cough, chronic rhinosinusitis and otitis media) who were found to be compound heterozygous for c.2303_2307delTAGAA (p.Leu768 Hisfs*5) and c.2318+1G>A (p. Splice) variants in CFAP221. Bronchiectasis was confirmed in two out of the three. All had situs solitus and normal ciliary EM but abnormalities of ciliary beating were seen in one subject on HSVMA. Immunofluorescence found absent CFAP221 protein in ciliated cells from one subject compared with controls. The authors cite data from a mouse model lacking this gene (PMID 18039845) who displayed reduced ciliary beat frequency, mucus accumulation in the sinuses and male infertility but it is not stated whether they had bronchiectasis.

There is one further report (PMID 39362668) of an individual born to consanguineous parents who was homozygous for a pathogenic frameshift variant c.1641dup (p.Asn548GlnfsTer6) who displayed a PCD phenotype of chronic respiratory symptoms, bronchiectasis, chronic rhinitis and chronic ear and hearing symptoms. As with the other reported cases they had situs solitus and normal EM, but in this case HSVMA found normal or only subtly changed ciliary beating.

Created: 18 Mar 2025, 3:19 p.m. | Last Modified: 18 Mar 2025, 3:19 p.m.

Panel Version: 3.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia

Publications

• 31636325
• 39362668

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is currently not associated with a phenotype in OMIM and Gene2Phenotype. There is not enough evidence to support a gene-disease association. This gene has been given a Red rating.

Created: 12 Oct 2021, 9:15 a.m. | Last Modified: 12 Oct 2021, 9:15 a.m.

Panel Version: 1.46

Red List (low evidence)

WES in 1 family with 3 siblings with clinical symptoms of PCD identified compound heterozygous loss-of-function variants in CFAP221, which segregated with disease. No functional studies. Nasal epithelial cells from 1 of the subjects demonstrated slightly reduced beat frequency, however, waveform analysis revealed that the CFAP221 defective cilia beat in an aberrant circular pattern. A candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.
Sources: Literature

Created: 11 Oct 2021, 9:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia

Publications

• 31636325