DNAAF6

Chr XXLR

dynein axonemal assembly factor 6

Also known as: CILD36, CXorf41, NYSAR97, PIH1D3, TWISTER

NCBI Gene: 139212 ENSG00000080572 UniProt: Q9NQM4 OMIM: 300933

DNAAF6 encodes a protein that enables dynein intermediate chain binding and is involved in cytoplasmic pre-assembly of axonemal dynein, which is essential for inner and outer dynein arm assembly in cilia and flagella. Mutations cause primary ciliary dyskinesia 36, an X-linked recessive disorder affecting respiratory tract function and sperm motility. The gene shows high constraint against loss-of-function variants (pLI 0.86, LOEUF 0.47), indicating intolerance to protein-disrupting mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables dynein intermediate chain binding activity. Involved in flagellated sperm motility; inner dynein arm assembly; and outer dynein arm assembly. Located in trans-Golgi network. Implicated in primary ciliary dyskinesia 36. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 36, X-linkedMIM #300991

XLR

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ciliary dyskinesia, primary, 36, X-linked · XL · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — DNAAF6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.855

Z-score 2.33

OE 0.00 (0.00–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.48Z-score

OE missense 0.84 (0.68–1.04)

57 obs / 68.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.47)

0≤0.351.4

Missense OE?0.84 (0.68–1.04)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 0 / 6.3Missense obs/exp: 57 / 68.0Syn Z: -0.80

Background carrier burden — how many people carry a rare variant somewhere in DNAAF6?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 520

149 rare PASS variants

Rare truncating (LoF)

1 in 60,000

8 rare PASS variants

Rare synonymous (reference)

1 in 1,500

50 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAAF6. 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)	~561k	1 in 570	1 in 80,000
South Asian	~36k	1 in 430	none seen
Remaining (unassigned)	~31k	1 in 220	≈ 1 in 30,000
European (Finnish)	~27k	1 in 4,500	≈ 1 in 27,000
Admixed American	~23k	1 in 860	none seen
African / African American	~21k	1 in 490	≈ 1 in 16,000
East Asian	~20k	1 in 370	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 980	none seen
Middle Eastern	~2,753	1 in 540	none seen

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓