DRC3

Chr 17

dynein regulatory complex subunit 3

Also known as: CFAP134, LRRC48

NCBI Gene: 83450 ENSG00000171962 UniProt: Q8TE68 OMIM: 618758

DRC3 encodes a protein that stimulates guanine exchange activity of SOS1 and is involved in membrane ruffling and actin cytoskeleton remodeling, while also localizing to the axoneme structure of cilia. Mutations cause primary ciliary dyskinesia, which typically presents in infancy or early childhood with chronic respiratory infections, sinusitis, and bronchiectasis due to defective ciliary function. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in flagellated sperm motility. Located in axoneme. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.40

OE 0.69 (0.47–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.22Z-score

OE missense 0.96 (0.88–1.06)

304 obs / 315.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.47–1.04)

0≤0.351.4

Missense OE?0.96 (0.88–1.06)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 17 / 24.5Missense obs/exp: 304 / 315.1Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in DRC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

722 rare PASS variants

Rare truncating (LoF)

1 in 1,000

119 rare PASS variants

Rare synonymous (reference)

1 in 160

280 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DRC3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.