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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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DNAAF3
dynein axonemal assembly factor 3
Chromosome 19 Β· 19q13.42
NCBI Gene: 352909Ensembl: ENSG00000167646.15HGNC: HGNC:30492UniProt: Q8N9W5
17PubMed Papers
21Diseases
0Drugs
52Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
motile cilium assemblyaxonemal dynein complex assemblydynein axonemal particlecytoplasmprimary ciliary dyskinesiaRare familial disorder with hypertrophic cardiomyopathyThrombocytopeniahypertrophic cardiomyopathy 4
✦AI Summary

DNAAF3 (dynein axonemal assembly factor 3) is essential for the assembly and transport of axonemal dynein complexes in motile cilia and flagella 1. The protein functions in the cytoplasmic preassembly of both inner and outer dynein arms before their incorporation into ciliary axonemes 23. DNAAF3 mutations cause primary ciliary dyskinesia (PCD), a rare autosomal recessive disorder characterized by defective ciliary motility 34. Patients typically present with situs inversus totalis, neonatal respiratory distress, chr19 sinusitis, and reduced nasal nitric oxide levels, though notably may lack recurrent lower airway infections 3. The gene is particularly significant in male fertility, as DNAAF3 mutations result in severe asthenozoospermia and teratospermia due to complete absence of outer dynein arms and partial absence of inner dynein arms in sperm flagella 25. Clinically, DNAAF3-related infertility can be successfully treated with intracytoplasmic sperm injection 2. Gene therapy approaches using lentiviral delivery have shown promise in restoring ciliary function in patient-derived organoid models 6. DNAAF3 mutations have been identified in multiple populations, expanding the genetic spectrum of PCD 47.

Sources cited
1
DNAAF3 is required for axonemal dynein assembly and is expressed in ciliated cells
PMID: 34553759
2
DNAAF3 mutations cause complete absence of outer dynein arms and partial absence of inner dynein arms in sperm
PMID: 37537752
3
DNAAF3 mutations cause PCD with situs inversus totalis, neonatal respiratory distress, and sinusitis
PMID: 31186518
4
DNAAF3 mutations are found in PCD patients worldwide
PMID: 33577779
5
DNAAF3 mutations result in severe asthenozoospermia and teratospermia
PMID: 39289782
6
Lentiviral gene therapy can restore DNAAF3 function in patient-derived organoids
PMID: 40947900
7
DNAAF3 mutations identified in Indian PCD patients
PMID: 39004944
Disease Associationsβ“˜21
primary ciliary dyskinesiaOpen Targets
0.79Strong
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.30Weak
ThrombocytopeniaOpen Targets
0.28Weak
hypertrophic cardiomyopathy 4Open Targets
0.26Weak
dilated cardiomyopathy 2AOpen Targets
0.16Weak
familial dilated cardiomyopathyOpen Targets
0.15Weak
cardiomyopathy, familial restrictive, 1Open Targets
0.15Weak
hypertrophic cardiomyopathy 7Open Targets
0.15Weak
DDX41-related hematologic malignancy predisposition syndromeOpen Targets
0.12Weak
HeterotaxiaOpen Targets
0.08Suggestive
heterotaxy, visceral, 12, autosomalOpen Targets
0.05Suggestive
ciliary dyskinesia, primary, 40Open Targets
0.05Suggestive
visceral heterotaxyOpen Targets
0.05Suggestive
Reduced sperm motilityOpen Targets
0.05Suggestive
ciliary dyskinesia, primary, 52Open Targets
0.04Suggestive
scimitar syndromeOpen Targets
0.04Suggestive
congenital heart diseaseOpen Targets
0.04Suggestive
ciliary dyskinesia, primary, 53Open Targets
0.04Suggestive
Ivemark syndromeOpen Targets
0.04Suggestive
right atrial isomerismOpen Targets
0.04Suggestive
Ciliary dyskinesia, primary, 2UniProt
Pathogenic Variants52
NM_001256715.2(DNAAF3):c.789+1G>CLikely pathogenic
Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2026
NM_001256715.2(DNAAF3):c.997dup (p.Asp333fs)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 2
β˜…β˜…β˜†β˜†2026β†’ Residue 333
NM_001256715.2(DNAAF3):c.265C>T (p.Arg89Ter)Pathogenic
Primary ciliary dyskinesia 2|Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 89
NM_001256715.2(DNAAF3):c.1195del (p.Ala399fs)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 399
NM_001256715.2(DNAAF3):c.350G>A (p.Trp117Ter)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 117
NM_001256715.2(DNAAF3):c.1271dup (p.Phe426fs)Pathogenic
Primary ciliary dyskinesia 2|Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 426
NM_001256715.2(DNAAF3):c.607_611dup (p.Arg205fs)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 2
β˜…β˜…β˜†β˜†2023β†’ Residue 205
NM_001256715.2(DNAAF3):c.548_558dup (p.Ser187delinsArgSerProTer)Pathogenic
Primary ciliary dyskinesia 2|Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2021β†’ Residue 187
NM_001256715.2(DNAAF3):c.901C>T (p.Gln301Ter)Pathogenic
Primary ciliary dyskinesia 2|Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2021β†’ Residue 301
NM_001256715.2(DNAAF3):c.-5+6G>APathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2026
NM_001256715.2(DNAAF3):c.86-64G>ALikely pathogenic
Primary ciliary dyskinesia|Sarcoma
β˜…β˜†β˜†β˜†2026
NM_001256715.2(DNAAF3):c.-5+7dupPathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025
NM_001256715.2(DNAAF3):c.62del (p.Pro21fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 21
NM_001256715.2(DNAAF3):c.-14G>APathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025
NM_001256715.2(DNAAF3):c.228+5G>CLikely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025
NM_001256715.2(DNAAF3):c.1051G>T (p.Ala351Ser)Likely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 351
NM_001256715.2(DNAAF3):c.842C>T (p.Pro281Leu)Likely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 281
NM_001256715.2(DNAAF3):c.842C>G (p.Pro281Arg)Likely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 281
NM_001256715.2(DNAAF3):c.1051G>A (p.Ala351Thr)Likely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 351
NM_001256715.2(DNAAF3):c.873_892del (p.Asp291fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 291
View on ClinVar β†—
Related Genes
CFAP298Protein interaction86%DNAAF6Protein interaction86%DNAH5Protein interaction78%DNALI1Protein interaction78%DNAH11Protein interaction78%ZMYND10Protein interaction78%
Tissue Expression6 tissues
Heart
100%
Lung
14%
Liver
9%
Brain
2%
Ovary
2%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
DNAAF3CFAP298DNAAF6DNAH5DNALI1DNAH11ZMYND10
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8N9W5
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.14LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.87 [0.67–1.14]
RankingsWhere DNAAF3 stands among ~20K protein-coding genes
  • #14,980of 20,598
    Most Researched17
  • #1,302of 5,498
    Most Pathogenic Variants52 Β· top quartile
  • #11,821of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedDNAAF3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China.
PMID: 33577779
Chest Β· 2021
1.00
2
A novel homozygous mutation in the DNAAF3 gene leads to severe asthenozoospermia and teratospermia.
PMID: 39289782
J Cell Mol Med Β· 2024
0.90
3
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
PMID: 39004944
Clin Genet Β· 2024
0.80
4
A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia.
PMID: 37537752
J Cell Mol Med Β· 2023
0.70
5
Functional characterization of DNAAF3-AS1 in chromatin remodeling and H3K36me3 distribution.
PMID: 41446072
bioRxiv Β· 2025
0.60