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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DNAH3
dynein axonemal heavy chain 3
Chromosome 16 · 16p12.3
NCBI Gene: 55567Ensembl: ENSG00000158486.15HGNC: HGNC:2949UniProt: A0A8V8TLI9
24PubMed Papers
20Diseases
0Drugs
4Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmsperm axoneme assemblyinner dynein arm assemblysperm flagellumspermatogenic failure 18Abnormality of the skeletal systemeye injurycoronary artery disease
✦AI Summary

DNAH3 (dynein axonemal heavy chain 3) is a force-generating motor protein of respiratory cilia and sperm flagella that produces force toward microtubule minus ends 1. The protein exhibits ATPase activity and is essential for assembling and organizing the sperm flagellum's axoneme, particularly the inner dynein arms 12. DNAH3 deficiency causes male infertility through multiple mechanisms. Biallelic DNAH3 variants have been identified in infertile men presenting with asthenozoospermia or oligoasthenoteratozoospermia (OAT), characterized by reduced sperm motility and flagellar morphological abnormalities 132. In affected patients, DNAH3 loss leads to decreased expression of IDA-associated proteins including DNAH1, DNAH6, and DNALI1, coupled with ultrastructural defects such as inner dynein arm loss, dislocated mitochondrial sheaths, and fibrous sheath abnormalities 12. Notably, DNAH3 deficiency can also impair sperm energy metabolism without flagellar morphological changes, reducing metabolites like L-palmitoylcarnitine and glycocholic acid 4. Clinically, DNAH3-associated male infertility can be effectively managed through intracytoplasmic sperm injection (ICSI), indicating the defect is exclusively in sperm motility function rather than fundamental genetic abnormality 124. These findings establish DNAH3 as a novel pathogenic gene for male infertility with diagnostic and prognostic implications.

Sources cited
1
DNAH3 resides in inner dynein arms; biallelic DNAH3 variants cause asthenoteratozoospermia with flagellar ultrastructure disruption and reduced IDA-associated protein expression; ICSI rescues infertility
PMID: 39503742
2
Novel biallelic DNAH3 mutations cause oligoasthenoteratozoospermia with multiple morphological abnormalities of sperm flagella; premature stop codons reduce DNAH3 protein expression
PMID: 39588341
3
DNAH3 is a novel candidate gene for asthenoteratozoospermia in humans and mice; mutations cause loss of central pair microtubules, dislocated mitochondrial and fibrous sheaths, and partial absence of inner dynein arms; ICSI successfully treats affected patients
PMID: 38312775
4
DNAH3 deficiency disturbs sperm energy metabolism with reduced L-palmitoylcarnitine and glycocholic acid; causes asthenozoospermia without abnormal flagellar morphology; ICSI produces offspring
PMID: 39774634
5
DNAH7 variants show marked reduction of DNAH3 and other IDA-associated proteins, supporting DNAH3's role in inner dynein arm assembly
PMID: 40810911
Disease Associationsⓘ20
spermatogenic failure 18Open Targets
0.49Moderate
Abnormality of the skeletal systemOpen Targets
0.36Weak
eye injuryOpen Targets
0.27Weak
coronary artery diseaseOpen Targets
0.24Weak
mixed connective tissue diseaseOpen Targets
0.24Weak
hypertensionOpen Targets
0.23Weak
Intellectual disabilityOpen Targets
0.12Weak
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
infertilityOpen Targets
0.06Suggestive
male infertilityOpen Targets
0.03Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
nervous system diseaseOpen Targets
0.02Suggestive
aortic diseaseOpen Targets
0.02Suggestive
heart failureOpen Targets
0.02Suggestive
COVID-19Open Targets
0.02Suggestive
Reduced sperm motilityOpen Targets
0.02Suggestive
squamous cell carcinomaOpen Targets
0.01Suggestive
thyroid gland oncocytic adenomaOpen Targets
0.01Suggestive
oligoasthenoteratozoospermiaOpen Targets
0.01Suggestive
Pathogenic Variants4
NM_001347886.2(DNAH3):c.10301G>A (p.Arg3434Gln)Likely pathogenic
Spermatogenic failure 18
★☆☆☆2023→ Residue 3434
NM_001347886.2(DNAH3):c.10122G>A (p.Trp3374Ter)Likely pathogenic
Spermatogenic failure 18
★☆☆☆2023→ Residue 3374
NM_001347886.2(DNAH3):c.6835T>C (p.Phe2279Leu)Likely pathogenic
Spermatogenic failure 18
★☆☆☆2023→ Residue 2279
NM_001347886.2(DNAH3):c.5005G>A (p.Gly1669Ser)Pathogenic
Spermatogenic failure 18
★☆☆☆2023→ Residue 1669
View on ClinVar ↗
Related Genes
DNAI2Protein interaction98%CFAP70Protein interaction92%SOD1Protein interaction80%DNAH7Protein interaction79%DNAL1Protein interaction79%DNAH5Protein interaction75%
Tissue Expression6 tissues
Heart
100%
Lung
88%
Brain
59%
Bone Marrow
20%
Liver
9%
Ovary
8%
Gene Interaction Network
Click a node to explore
DNAH3DNAI2CFAP70SOD1DNAH7DNAL1DNAH5
PROTEIN STRUCTURE
Preparing viewer…
PDB8J07 · 4.10 Å · EM
View on RCSB ↗
RankingsWhere DNAH3 stands among ~20K protein-coding genes
  • #13,174of 20,598
    Most Researched24
  • #3,847of 5,498
    Most Pathogenic Variants4
Genes detectedDNAH3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice.
PMID: 39503742
Elife · 2024
1.00
2
Novel bi-allelic DNAH3 variants cause oligoasthenoteratozoospermia.
PMID: 39588341
Front Endocrinol (Lausanne) · 2024
0.90
3
Bi-allelic variants in
PMID: 38312775
Hum Reprod Open · 2024
0.80
4
Impact of DNAH3 deficiency on sperm energy metabolism and motility leading to asthenozoospermia†.
PMID: 39774634
Biol Reprod · 2025
0.70
5
Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans.
PMID: 40810911
Hum Genet · 2025
0.60