DNAH5

Chr 5AR

dynein axonemal heavy chain 5

Also known as: CILD3, DNAHC5, HL1, KTGNR, PCD

NCBI Gene: 1767ENSG00000039139UniProt: Q8TE73

This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 3, with or without situs inversusMIM #608644
AR
572
ClinVar variants
62
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAH5
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 3 · 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
62 Pathogenic / Likely Pathogenic· 375 VUS of 572 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.
0.69LOEUF
pLI 0.000
Z-score 5.61
OE 0.60 (0.53–0.69)
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.
-0.77Z-score
OE missense 1.04 (1.01–1.08)
2582 obs / 2474.1 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.0.60 (0.53–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (1.01–1.08)
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.1.05
0≤1.21.6
LoF obs/exp: 141 / 233.5Missense obs/exp: 2582 / 2474.1Syn Z: -1.16

ClinVar Variant Classifications

572 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic26
VUS375
Likely Benign133
Conflicting2
36
Pathogenic
26
Likely Pathogenic
375
VUS
133
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
14
0
36
Likely Pathogenic
18
2
6
0
26
VUS
0
295
24
56
375
Likely Benign
0
5
66
62
133
Benign
0
0
0
0
0
Conflicting
—2
Total40302110118572

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAH5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DNAH5-related primary ciliary dyskinesia

strong
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, 3, with or without situs inversus

MIM #608644

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DNAH5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China.
Guan Y et al.·Chest
2021
Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.
Davis SD et al.·Am J Respir Crit Care Med
2019Natural history
Genetic spectrum and genotype-phenotype correlations in DNAH5-mutated primary ciliary dyskinesia: a systematic review.
Dong M et al.·Orphanet J Rare Dis
2025Review
Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML.
Yang F et al.·Blood
2022Clinical trial
Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis.
Zhang RL et al.·Chest
2023
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
Jat KR et al.·Clin Genet
2024Cohort
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
Whole genome sequencing enhances molecular diagnosis of primary ciliary dyskinesia.
Black HA et al.·Pediatr Pulmonol
2024
Identification and validation of a prognostic-related mutant gene DNAH5 for hepatocellular carcinoma.
Song Z et al.·Front Immunol
2023
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.
Bolkier Y et al.·J Med Genet
2022
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