CFAP300

protein-coding

cilia and flagella associated protein 300, the group of Cilia and flagella associated

Gene summary

Predicted to be located in cytoplasm and motile cilium. Implicated in primary ciliary dyskinesia 38. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C11orf70

MANE transcript

NM_032930.3

Inheritance

AR, AD

ClinVar variants

P:19U:27B:41

Top phenotype

Ciliary dyskinesia, primary, 38

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr11:102,047,437-102,084,554

External References & Databases

Ensembl (ENSG00000137691)

Transcript & Mutation Effects

hg38 • Region Span ~37.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ciliary dyskinesia, primary, 38DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0054843

Submitter: ClinGen

CFAP300 (C11orf70) was first characterized as an evolutionarily conserved protein essential for assembly of dynein arms with the gene variants reported in a cohort of PCD affected children in 2018 (PMID: 29727692). Reported cases showed a consistent PCD phenotype with recurrent respiratory tract infection, neonatal respiratory distress and reduced nasal nitric oxide along with immotile respiratory cilia displaying combined loss of inner and outer dynein arms (IDA+ODA). Laterality defects were observed in some of the investigated PCD-affected individuals with biallelic *CFAP300* mutations (PMIDs:29727692, 29727693 and 30916986). Fertility defects are also reported in both male and female patients (PMID: 29727693). Seven (missense, splice site, and frameshift) variants that have been reported in 3 publications are used in this curation (PMIDs: 29727692, 29727693 and 30916986). Mechanism of pathogenicity appears to be loss of function resulting in defects in the dynein-arm assembly machinery (PMID: 29727693). Phylogenetic analysis shows that C11orf70 is expressed in species that require dynein arms for cilia motility (PMID:29727692). RNAi knockdown of the Paramecium *C11orf70* ortholog led to combined loss of ciliary IDA+ODA with reduced cilia beating and swim velocity (PMID:29727692). *C11orf70* shows a similar RNA expression profile to genes involved in dynein arm assembly, and to those coding for structural dynein arm proteins (PMID: 30916986). High resolution immunofluorescence revealed that the ODA components DNAH5, DNAH9, DNAI1, and DNAI2 as well as IDA components (DNALI1 and DNAH6) were absent or severely reduced from the respiratory ciliary axonemes of the affected individuals (PMIDs:29727693 and 30916986). The identification of *FBB5*, the Chlamydomonas *CFAP300* ortholog, as a member of a group of flagellar basal body genes and the cytoplasmic apical localization of the dynein arm components (DNAH5, DNAI2, and DNALI1) by IF in patients carrying biallelic *CFAP300* mutations, suggest a role of CFAP300 in dynein arm transport within the axoneme (PMID: 30916986). In summary, *CFAP300* is definitively associated with primary ciliary dyskinesia 38. This has been repeatedly demonstrated in both clinical diagnostic and research settings and has been upheld over time without the emergence of contradictory evidence, leading to a definitive classification.This classification was approved by the ClinGen Motile Ciliopathy GCEP on September 8, 2022 (SOP Version 9).

primary ciliary dyskinesiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016575

Submitter: Orphanet

ciliary dyskinesia, primary, 38DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0054843

Submitter: G2P

ciliary dyskinesia, primary, 38STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054843

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Ciliary dyskinesia, primary, 38AR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary

Intervention: Audiologic/Otolaryngologic; Cardiovascular; Pulmonary

Rationale: Among other findings, patients can manifest with early-onset respiratory disease, including upper respiratory infections, and awareness may allow early interventions related to these sequelae; The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 29727692; 29727693

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFAP300 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 108

not specifiedTotal: 14

Ciliary dyskinesia, primary, 38Total: 12

CFAP300-related disorderTotal: 8

Primary ciliary dyskinesiaTotal: 3

Inborn genetic diseasesTotal: 3

Kartagener syndromeTotal: 2

C11ORF70 & CFAP300-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032930.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				33 clinvar	2 clinvar	35
missense		2 clinvar	26 clinvar	5 clinvar	1 clinvar	34
nonsense	8 clinvar	2 clinvar				10
start loss						0
frameshift	4 clinvar	1 clinvar				5
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	13	6	27	38	3	87

Highest pathogenic variant AF is 0.00028927843

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032930.3	RefSeq	NP_116319.2	7	MANE Select
ENST00000434758.7	Ensembl	ENSP00000414390.2	7	MANE Select
NM_001195005.2	RefSeq	NP_001181934.1	4	Standard
NM_001363505.2	RefSeq	NP_001350434.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

cytoplasm
cytoskeleton
motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000434758
Coding exons: 7
Length: 37118
Individuals with no LoFs: 125569
Homozygous LoFs: 0
Heterozygous LoFs: 178
Defined: 125747
p: 0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.102	137	140	0.976	0.00000684	1745
Missense (PolyPhen)		41	41.131	0.99681		553
Synonymous	0.142	47	48.3	0.974	0.00000228	487
Loss of Function	1.15	11	16.0	0.689	9.34e-7	185

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000067	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.0055	0.0054	notable
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00024	0.00023	rare
Other	0.00052	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. May play a role in outer and inner dynein arm assembly. {ECO:0000250|UniProtKB:A0CY51}.;
Disease: DISEASE: Note=Defects in CFAP300 are a cause of primary ciliary dyskinesia (PCD), a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. {ECO:0000269|PubMed:29727692, ECO:0000269|PubMed:29727693}.;

Recessive Scores

pRec: 0.0947

Intolerance Scores

RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (gene trap): N