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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DNAAF1
dynein axonemal assembly factor 1
Chromosome 16 Β· 16q24.1
NCBI Gene: 123872Ensembl: ENSG00000154099.19HGNC: HGNC:30539UniProt: A0A140VJN4
22PubMed Papers
21Diseases
0Drugs
52Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
dynein complex bindingheart loopingcilium movementregulation of cilium beat frequencyprimary ciliary dyskinesiabronchiectasisHeterotaxyvisceral heterotaxy
✦AI Summary

DNAAF1 (dynein axonemal assembly factor 1) is a cytoplasmic protein essential for ciliary function and cardiac development. Functionally, DNAAF1 is required for dynein heavy chain assembly and the stability of ciliary architecture, playing a central role in cytoplasmic preassembly of dynein-arm complexes 1. The protein interacts with ciliary intraflagellar transport proteins and AAA+ ATPases (RUVBL1 and RUVBL2), interactions critical for proper cilia motility and asymmetric left-right patterning during development 1. Disease relevance is substantial. DNAAF1 mutations cause primary ciliary dyskinesia (PCD), characterized by defective ciliary motility, infertility, bronchiectasis, and sinusitis 23. Beyond PCD, DNAAF1 mutations are associated with heterotaxy and congenital heart defects 14, neural tube defects 5, adolescent idiopathic scoliosis 6, and testicular germ cell tumors 7, suggesting broader roles in developmental morphogenesis and cancer susceptibility. Clinically, whole-exome sequencing identifies DNAAF1 mutations in ~56% of laterality disorder cases 4. Gene therapy shows promise: lentiviral vectors successfully restore DNAAF1 expression and ciliary function in patient-derived airway organoids 8, providing proof-of-concept for targeted therapeutic approaches.

Sources cited
1
DNAAF1 is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility; mutations cause PCD; interacts with IFT88, RUVBL1, and RUVBL2; has role in heart laterality and left-right asymmetry
PMID: 29228333
2
DNAAF1 mutations identified in patients with heterotaxy and congenital heart defects; whole-exome sequencing reaches molecular diagnosis in 56.7% of laterality disorder patients
PMID: 34215651
3
DNAAF1 mutations associated with testicular germ cell tumor susceptibility; 8.7% of TGCT families carry rare disruptive mutations in ciliary genes including DNAAF1
PMID: 27996046
4
DNAAF1 mutations contribute to neural tube defects; protein involved in cytoplasmic preassembly of dynein-arm complexes; expressed in neural tube and embryonic node
PMID: 27543293
5
Novel DNAAF1 mutations identified in PCD patients with Kartagener syndrome; mutations result in inner and outer dynein arm defects and loss of ciliary motility
PMID: 33174003
6
Lentiviral gene delivery successfully restores DNAAF1 expression in patient-derived airway organoids, improving ciliary beating frequency and function
PMID: 40947900
7
DNAAF1 knockout in zebrafish recapitulates scoliosis phenotype; dynein axonemal assembly factors associated with adolescent idiopathic scoliosis susceptibility
PMID: 33251213
8
Homozygous DNAAF1 mutations cause primary ciliary dyskinesia with outer and inner dynein arm defects
PMID: 38432987
Disease Associationsβ“˜21
primary ciliary dyskinesiaOpen Targets
0.77Strong
bronchiectasisOpen Targets
0.37Weak
HeterotaxyOpen Targets
0.33Weak
visceral heterotaxyOpen Targets
0.33Weak
uveitisOpen Targets
0.27Weak
Romano-Ward syndromeOpen Targets
0.07Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.07Suggestive
familial atrial fibrillationOpen Targets
0.07Suggestive
Brugada syndromeOpen Targets
0.07Suggestive
seminomaOpen Targets
0.06Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.06Suggestive
Familial short QT syndromeOpen Targets
0.06Suggestive
hypertrophic cardiomyopathyOpen Targets
0.06Suggestive
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.06Suggestive
atrial fibrillationOpen Targets
0.06Suggestive
Wolff-Parkinson-White SyndromeOpen Targets
0.05Suggestive
dilated cardiomyopathyOpen Targets
0.05Suggestive
familial sick sinus syndromeOpen Targets
0.05Suggestive
Atrial tachyarrhythmia with short PR intervalOpen Targets
0.05Suggestive
Lown-Ganong-Levine syndromeOpen Targets
0.05Suggestive
Ciliary dyskinesia, primary, 13UniProt
Pathogenic Variants52
NM_178452.6(DNAAF1):c.1906C>T (p.Arg636Ter)Pathogenic
Primary ciliary dyskinesia|Respiratory ciliopathies including non-CF bronchiectasis
β˜…β˜…β˜†β˜†2025β†’ Residue 636
NM_178452.6(DNAAF1):c.1300_1322del (p.Gly434fs)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 13|DNAAF1-related disorder|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 434
NM_178452.6(DNAAF1):c.1012del (p.Arg338fs)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 13
β˜…β˜…β˜†β˜†2025β†’ Residue 338
NM_178452.6(DNAAF1):c.190C>T (p.Gln64Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2025β†’ Residue 64
NM_178452.6(DNAAF1):c.778C>T (p.Gln260Ter)Pathogenic
Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 260
NM_178452.6(DNAAF1):c.792C>A (p.Tyr264Ter)Pathogenic
Primary ciliary dyskinesia 13|Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2024β†’ Residue 264
NM_178452.6(DNAAF1):c.985C>T (p.Gln329Ter)Pathogenic
DNAAF1-related disorder|Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2023β†’ Residue 329
NM_178452.6(DNAAF1):c.1031-2A>GLikely pathogenic
Primary ciliary dyskinesia 13
β˜…β˜†β˜†β˜†2026
NM_178452.6(DNAAF1):c.1957G>T (p.Glu653Ter)Pathogenic
DNAAF1-related disorder|Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 653
NM_178452.6(DNAAF1):c.205_212del (p.Gly69fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 69
NM_178452.6(DNAAF1):c.106C>T (p.Arg36Ter)Likely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 36
NM_178452.6(DNAAF1):c.942_943delinsAT (p.Lys315Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 315
NM_178452.6(DNAAF1):c.285dup (p.Leu96fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 96
NM_178452.6(DNAAF1):c.515del (p.Leu172fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 172
NM_178452.6(DNAAF1):c.1462C>T (p.Arg488Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 488
NM_178452.6(DNAAF1):c.58C>T (p.Gln20Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 20
NM_178452.6(DNAAF1):c.1450G>T (p.Glu484Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 484
NM_178452.6(DNAAF1):c.1484del (p.Pro495fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2024β†’ Residue 495
NM_178452.6(DNAAF1):c.1618G>T (p.Glu540Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2024β†’ Residue 540
NM_178452.6(DNAAF1):c.934_940del (p.Arg312fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2024β†’ Residue 312
View on ClinVar β†—
Related Genes
RPGRProtein interaction94%SPAG1Protein interaction94%DNALI1Protein interaction94%ZMYND10Protein interaction94%DNAAF5Protein interaction94%RSPH4AProtein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
34%
Ovary
18%
Brain
14%
Liver
7%
Heart
3%
Gene Interaction Network
Click a node to explore
DNAAF1RPGRSPAG1DNALI1ZMYND10DNAAF5RSPH4A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8NEP3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.14LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.92 [0.76–1.14]
RankingsWhere DNAAF1 stands among ~20K protein-coding genes
  • #13,647of 20,598
    Most Researched22
  • #1,301of 5,498
    Most Pathogenic Variants52 Β· top quartile
  • #11,757of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedDNAAF1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport.
PMID: 29228333
Hum Mol Genet Β· 2018
1.00
2
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.
PMID: 34215651
J Med Genet Β· 2022
0.90
3
Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility.
PMID: 27996046
Nat Commun Β· 2016
0.80
4
Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans.
PMID: 27543293
G3 (Bethesda) Β· 2016
0.70
5
Novel dynein axonemal assembly factor 1 mutations identified using whole‑exome sequencing in patients with primary ciliary dyskinesia.
PMID: 33174003
Mol Med Rep Β· 2020
0.60