DNAAF11

Chr 8AR

dynein axonemal assembly factor 11

Also known as: CILD19, LRRC6, LRTP, TSLRP, tilB

NCBI Gene: 23639 ENSG00000129295 UniProt: Q86X45 OMIM: 614930

The protein is involved in dynein arm assembly and transports outer dynein arm proteins from the cytoplasm to cilia, making it crucial for ciliary motility and sperm flagella formation. Mutations cause primary ciliary dyskinesia-19, a condition affecting respiratory function, fertility, and organ positioning due to defective ciliary motility. This follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 19MIM #614935

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · primary ciliary dyskinesia 19 · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — DNAAF11

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?

1.08LOEUF

pLI 0.000

Z-score 1.23

OE 0.74 (0.51–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.02 (0.92–1.14)

243 obs / 237.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.51–1.08)

0≤0.351.4

Missense OE?1.02 (0.92–1.14)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 19 / 25.7Missense obs/exp: 243 / 237.4Syn Z: -0.14

Background carrier burden — how many people carry a rare variant somewhere in DNAAF11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 64

610 rare PASS variants

Rare truncating (LoF)

1 in 750

138 rare PASS variants

Rare synonymous (reference)

1 in 210

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAAF11. 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 100	1 in 990
South Asian	~43k	1 in 53	1 in 760
Remaining (unassigned)	~30k	1 in 61	1 in 940
European (Finnish)	~27k	1 in 660	≈ 1 in 8,900
Admixed American	~22k	1 in 97	1 in 1,600
African / African American	~21k	1 in 100	1 in 510
East Asian	~20k	1 in 120	1 in 540
Ashkenazi Jewish	~13k	1 in 370	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 63	≈ 1 in 2,800

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): 8 of 12 coding exons well covered in gnomAD exomes; exon 3 poorly covered; exons 1, 8, 9 marginal. Genomes: all 12.? see exons ↓