DNAI3

Chr 1

dynein axonemal intermediate chain 3

Also known as: DIC3, NYD-SP29, WDR63

NCBI Gene: 126820 ENSG00000162643 UniProt: Q8IWG1 OMIM: 617968

DNAI3 encodes a protein that negatively regulates cell migration through inhibition of Arp2/3 complex-mediated actin polymerization and is potentially involved in ciliary function through association with axonemal dynein complexes. Mutations cause primary ciliary dyskinesia with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern of associated ciliopathy.

OMIM ResearchSummary from RefSeq, UniProt

Enables Arp2/3 complex binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation and negative regulation of cell migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 2.98

OE 0.56 (0.41–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.02Z-score

OE missense 0.87 (0.80–0.94)

410 obs / 472.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.41–0.76)

0≤0.351.4

Missense OE?0.87 (0.80–0.94)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 29 / 52.2Missense obs/exp: 410 / 472.3Syn Z: 0.34

Background carrier burden — how many people carry a rare variant somewhere in DNAI3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

1,090 rare PASS variants

Rare truncating (LoF)

1 in 300

197 rare PASS variants

Rare synonymous (reference)

1 in 140

343 rare PASS variants

Rare missense and truncating variants are carried at similar rates in DNAI3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 800
South Asian	~43k	1 in 62	1 in 370
Remaining (unassigned)	~30k	1 in 59	1 in 390
European (Finnish)	~27k	1 in 210	1 in 530
Admixed American	~22k	1 in 65	1 in 450
African / African American	~21k	1 in 56	1 in 460
East Asian	~20k	1 in 63	1 in 810
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 87	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 22 coding exons well covered in gnomAD exomes; exons 3, 6, 8 marginal. Genomes: all 22.? see exons ↓