DNAI4

Chr 1

dynein axonemal intermediate chain 4

Also known as: DIC4, WDR78

The DNAI4 protein is critical for assembly of axonemal dynein complexes that drive ciliary motility. Mutations cause primary ciliary dyskinesia with autosomal recessive inheritance, affecting the respiratory system, fertility, and potentially laterality determination. This gene shows extremely low constraint against loss-of-function variants (pLI near 0), consistent with recessive disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
24
P/LP submissions
0%
P/LP missense
0.93
LOEUF
DN
Mechanism· predicted
Clinical SummaryDNAI4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 135 VUS of 192 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.92
OE 0.70 (0.530.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.931.09)
438 obs / 434.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.530.93)
00.351.4
Missense OE1.01 (0.931.09)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 33 / 47.3Missense obs/exp: 438 / 434.4Syn Z: -0.47
DN
0.6357th %ile
GOF
0.4481th %ile
LOF
0.4529th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

ClinVar Variant Classifications

192 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS135
Likely Benign12
22
Pathogenic
2
Likely Pathogenic
135
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
2
0
2
VUS
0
127
8
0
135
Likely Benign
0
12
0
0
12
Benign
0
0
0
0
0
Total0139320171

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAI4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found