DNAH3

Chr 16

dynein axonemal heavy chain 3

ENSG00000158486UniProt: Q8TD57

Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly (By similarity). Essential for the assembly and structural organization of the sperm flagellum's axoneme, including its inner dynein arms and accessory components, which are critical for maintaining flagellar integrity and motility (PubMed:39503742, PubMed:38312775)

195
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAH3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
184 VUS of 195 total submissions
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 3.96
OE 0.69 (0.60–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.03Z-score
OE missense 1.00 (0.96–1.03)
2256 obs / 2260.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.60–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.96–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 132 / 191.1Missense obs/exp: 2256 / 2260.0Syn Z: -2.13

ClinVar Variant Classifications

195 submitted variants in ClinVar

ClinVar

Classification Summary

VUS184
Likely Benign10
Conflicting1
184
VUS
10
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
2
181
1
0
184
Likely Benign
0
9
0
1
10
Benign
0
0
0
0
0
Conflicting
—1
Total219011195

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DNAH3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice.
Wang X et al.·Elife
2024
Novel bi-allelic DNAH3 variants cause oligoasthenoteratozoospermia.
Li S et al.·Front Endocrinol (Lausanne)
2024
Impact of DNAH3 deficiency on sperm energy metabolism and motility leading to asthenozoospermia†.
Li J et al.·Biol Reprod
2025
Biallelic loss-of-function variants of DNAH7 cause male infertility associated with asthenozoospermia in humans.
Zhao G et al.·Hum Genet
2025
Mutational and transcriptional profile predicts the prognosis of stage IV gastric cancer - Prognostic factors for metastatic gastric cancer.
Xie Z et al.·Arab J Gastroenterol
2024
Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland.
Järvelä I et al.·Hum Genet
2021
Narrow Versus Broad Phenotype Definitions Affect Genetic Analysis of Language More than Other Broad Autism Phenotype Traits.
Lodi MK et al.·Genes (Basel)
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools