DNAAF1

Chr 16AR

dynein axonemal assembly factor 1

Also known as: CILD13, DAU1, LRRC50, ODA7, swt

NCBI Gene: 123872 ENSG00000154099 UniProt: Q8NEP3 OMIM: 613190

This gene encodes a cilium-specific protein required for the stability of ciliary architecture and cytoplasmic preassembly of dynein arms. Mutations cause primary ciliary dyskinesia-13, an autosomal recessive disorder affecting respiratory function, fertility, and often causing situs inversus due to defective cilia motility. The gene is highly constrained against loss-of-function variants in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.001 OMIM phenotype

Clinical Summary— DNAAF1

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Gene-Disease Validity (ClinGen)

primary ciliary dyskinesia 13 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

67 unique Pathogenic / Likely Pathogenic· 335 VUS of 766 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — DNAAF1

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?

1.00LOEUF

pLI 0.000

Z-score 1.56

OE 0.70 (0.50–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.99Z-score

OE missense 1.28 (1.19–1.38)

502 obs / 391.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.70 (0.50–1.00)

0≤0.351.4

Missense OE?1.28 (1.19–1.38)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 22 / 31.4Missense obs/exp: 502 / 391.4Syn Z: -1.74

This gene — mechanism propensity

0.7035th %ile

GOF

0.77top 25%

LOF

0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

766 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50

Likely Pathogenic17

VUS335

Likely Benign227

Benign78

Conflicting50

Pathogenic

Likely Pathogenic

335

VUS

227

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	41	1	8	0	50
Likely Pathogenic	16	1	0	0	17
VUS	6	310	17	2	335
Likely Benign	0	23	66	138	227
Benign	0	13	60	5	78
Conflicting	—				50
Total	63	348	151	145	757

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

View in ClinVar →

45 pathogenic / likely-pathogenic (of 78) ClinVar copy-number / structural variants overlap DNAAF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →