DNAH9

Chr 17AR

dynein axonemal heavy chain 9

NCBI Gene: 1770ENSG00000007174UniProt: Q9NYC9

Force generating protein required for cilia beating in respiratory epithelia (PubMed:30471717, PubMed:30471718). Produces force towards the minus ends of microtubules (PubMed:30471717, PubMed:30471718). 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:30471717, PubMed:30471718). Required for structural and functional integrity of cilia (PubMed:30471717, PubMed:30471718)

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 40MIM #618300
AR
579
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAH9
🧬
Gene-Disease Validity (ClinGen)
ciliary dyskinesia, primary, 40 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 281 VUS of 579 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.
0.72LOEUF
pLI 0.000
Z-score 5.03
OE 0.62 (0.54–0.72)
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.
-0.04Z-score
OE missense 1.00 (0.97–1.04)
2436 obs / 2430.0 exp
Tolerant

Tolerant to missense variation

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.0.62 (0.54–0.72)
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 (0.97–1.04)
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.0.97
0≤1.21.6
LoF obs/exp: 130 / 208.4Missense obs/exp: 2436 / 2430.0Syn Z: 0.64

ClinVar Variant Classifications

579 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic9
VUS281
Likely Benign250
Benign5
Conflicting6
28
Pathogenic
9
Likely Pathogenic
281
VUS
250
Likely Benign
5
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
13
0
28
Likely Pathogenic
8
0
1
0
9
VUS
0
273
8
0
281
Likely Benign
1
7
78
164
250
Benign
0
0
2
3
5
Conflicting
—6
Total23281102167579

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAH9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DNAH9-related motile cilia defects and situs inversus

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ciliary dyskinesia, primary, 40

MIM #618300

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DNAH9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
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
Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML.
Yang F et al.·Blood
2022Clinical trial
The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.
Rio-Machin A et al.·Nat Commun
2020
Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening.
Zheng R et al.·Cell Death Dis
2022Cohort
Novel compound heterozygous mutation in DNAH9 causes complex congenital heart disease.
Liu X et al.·Mol Med Rep
2025
Novel variants in DNAH9 are present in two infertile patients with severe asthenospermia.
Yan F et al.·J Hum Genet
2025Case report
DNAH9 variants in children with post-infectious bronchiolitis/bronchitis obliterans.
Guan Y et al.·Orphanet J Rare Dis
2025
Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non-Small-Cell Lung Cancer.
Yue D et al.·J Clin Oncol
2022Clinical trial
Recessive DNAH9 Loss-of-Function Mutations Cause Laterality Defects and Subtle Respiratory Ciliary-Beating Defects.
Loges NT et al.·Am J Hum Genet
2018
Genetic diagnosis for adult patients at a genetic clinic.
Rojnueangnit K et al.·Cold Spring Harb Mol Case Stud
2022Cohort
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