DNAH8

Chr 6AR

dynein axonemal heavy chain 8

NCBI Gene: 1769ENSG00000124721UniProt: Q96JB1

Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum (PubMed:32619401). Produces force towards the minus ends of microtubules (PubMed:32619401). Key component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (PubMed:32619401). Involved in sperm motility; implicated in sperm flagellar assembly (PubMed:32619401)

Primary Disease Associations & Inheritance

Spermatogenic failure 46MIM #619095
AR
595
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAH8
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia · ARDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 281 VUS of 595 total submissions

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.
0.68LOEUF
pLI 0.000
Z-score 5.85
OE 0.59 (0.51–0.68)
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.
1.21Z-score
OE missense 0.93 (0.90–0.96)
2129 obs / 2291.6 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.0.59 (0.51–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.90–0.96)
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.0.98
0≤1.21.6
LoF obs/exp: 136 / 232.2Missense obs/exp: 2129 / 2291.6Syn Z: 0.44

ClinVar Variant Classifications

595 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic12
VUS281
Likely Benign255
Benign9
38
Pathogenic
12
Likely Pathogenic
281
VUS
255
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
16
0
38
Likely Pathogenic
11
0
1
0
12
VUS
3
261
15
2
281
Likely Benign
0
3
119
133
255
Benign
0
0
8
1
9
Total36264159136595

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAH8 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spermatogenic failure 46

MIM #619095

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Whole exome sequencing analysis of 167 men with primary infertility.
Zhou H et al.·BMC Med Genomics
2024
Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype.
Staar BO et al.·Cells
2023
A novel splicing variant in DNAH8 causes asthenozoospermia.
Zhou Z et al.·J Assist Reprod Genet
2021
A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family.
Dil S et al.·Asian J Androl
2023
Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility.
Liu C et al.·Am J Hum Genet
2020
A lipid metabolism-based prognostic risk model for HBV-related hepatocellular carcinoma.
Zhou L et al.·Lipids Health Dis
2023Functional
Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression.
Wang Y et al.·Oncotarget
2016
Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility.
Sudhakar DVS et al.·Hum Mol Genet
2023Functional
Mutations in DNAH8 contribute to multiple morphological abnormalities of sperm flagella and male infertility.
Weng M et al.·Acta Biochim Biophys Sin (Shanghai)
2021
Beyond environmental risk: Genetic insights into lung cancer susceptibility through whole exome analysis.
Lintas C et al.·Lung Cancer
2025
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