DNAI1

Chr 9AR

dynein axonemal intermediate chain 1

Also known as: CILD1, DIC1, ICS1, PCD, oda6

NCBI Gene: 27019ENSG00000122735UniProt: Q9UI46

This gene encodes a member of the dynein intermediate chain family. The encoded protein is part of the dynein complex in respiratory cilia. The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia and Kartagener syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 1, with or without situs inversusMIM #244400
AR
UniProtKartagener syndrome
1137
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— DNAI1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 171 VUS of 1137 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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 2.91
OE 0.49 (0.34–0.72)
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.
-0.29Z-score
OE missense 1.04 (0.96–1.14)
382 obs / 366.2 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.0.49 (0.34–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.96–1.14)
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.1.17
0≤1.21.6
LoF obs/exp: 19 / 38.4Missense obs/exp: 382 / 366.2Syn Z: -1.64

ClinVar Variant Classifications

1137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic24
VUS171
Likely Benign248
Benign4
Conflicting3
45
Pathogenic
24
Likely Pathogenic
171
VUS
248
Likely Benign
4
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
1
21
0
45
Likely Pathogenic
15
2
7
0
24
VUS
0
145
14
12
171
Likely Benign
1
4
155
88
248
Benign
0
0
4
0
4
Conflicting
—3
Total39152201100495

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAI1 · 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

Ciliary dyskinesia, primary, 1, with or without situs inversus

MIM #244400

Molecular basis of disorder known

Autosomal recessive
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
Inhaled DNAI1 mRNA therapy for treatment of primary ciliary dyskinesia.
Hennig M et al.·Proc Natl Acad Sci U S A
2025
Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis.
Zhang RL et al.·Chest
2023
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
Lipid nanoparticle-encapsulated Dnai1 mRNA rescues ciliary activity in primary ciliary dyskinesia mouse cell models.
Smith AJ et al.·J Cell Sci
2025Functional
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
Jat KR et al.·Clin Genet
2024Cohort
Genetic causes of bronchiectasis: primary ciliary dyskinesia.
Morillas HN et al.·Respiration
2007Review
DNAI1 mutations explain only 2% of primary ciliary dykinesia.
Failly M et al.·Respiration
2008
Variant of uncertain significance in the DNAI1 gene in a child with typical primary ciliary dyskinesia phenotype.
Nuñez-Paucar H et al.·Bol Med Hosp Infant Mex
2025Case report
Genetic defects in ciliary structure and function.
Zariwala MA et al.·Annu Rev Physiol
2007Review
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
Primary Ciliary Dyskinesia (PCD)

Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance

ACTIVE NOT RECRUITING
NCT06633757Phase PHASE1ReCode TherapeuticsStarted 2024-10-22
RCT1100
Primary Ciliary Dyskinesia

A Study Providing Genetic Testing to Find Those Who May Have Primary Ciliary Dyskinesia for Potential Clinical Trials

ACTIVE NOT RECRUITING
NCT06172374ReCode TherapeuticsStarted 2023-08-31
Sano Genetics Testing Kit

External Resources

Links to major genomics databases and tools