DNAI1

Chr 9AR

dynein axonemal intermediate chain 1

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

NCBI Gene: 27019ENSG00000122735UniProt: Q9UI46OMIM: 604366

The DNAI1 protein is a component of the dynein motor complex that generates force for ciliary movement in respiratory cilia and is required for structural and functional integrity of cilia. Mutations cause primary ciliary dyskinesia with or without situs inversus (Kartagener syndrome), affecting respiratory function and potentially organ positioning. This condition follows autosomal recessive inheritance and typically presents in early childhood with chronic respiratory symptoms.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.721 OMIM phenotype
Clinical Summary— DNAI1
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Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 117 VUS of 300 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — DNAI1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.000
Z-score 2.91
OE 0.49 (0.34–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.29Z-score
OE missense 1.04 (0.96–1.14)
382 obs / 366.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.49 (0.34–0.72)
0≤0.351.4
Missense OE1.04 (0.96–1.14)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 19 / 38.4Missense obs/exp: 382 / 366.2Syn Z: -1.64
DN
0.7133th %ile
GOF
0.4382th %ile
LOF
0.4234th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF75% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic35
VUS117
Likely Benign120
Benign2
21
Pathogenic
35
Likely Pathogenic
117
VUS
120
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
10
0
21
Likely Pathogenic
31
0
4
0
35
VUS
0
95
11
11
117
Likely Benign
0
3
54
63
120
Benign
0
0
2
0
2
Total42988174295

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients