DNAAF8

Chr 16

dynein axonemal assembly factor 8

Also known as: C16orf71, Daap1

NCBI Gene: 146562 ENSG00000166246 UniProt: Q8IYS4

This protein enables dynein complex binding and is required for deployment of outer dynein arms to the axoneme in ciliated cells. Mutations cause primary ciliary dyskinesia, a disorder affecting respiratory function, fertility, and organ positioning that typically presents in infancy or early childhood. Primary ciliary dyskinesia follows autosomal recessive inheritance.

ResearchSummary from RefSeq, UniProt

Predicted to enable dynein complex binding activity. Predicted to be involved in outer dynein arm assembly. Located in dynein axonemal particle. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.52

Clinical Summary— DNAAF8

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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

7 VUS of 18 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.000

Z-score -0.50

OE 1.11 (0.82–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.41Z-score

OE missense 1.23 (1.13–1.34)

368 obs / 299.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.82–1.52)

0≤0.351.4

Missense OE?1.23 (1.13–1.34)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 28 / 25.3Missense obs/exp: 368 / 299.2Syn Z: -1.02

This gene — mechanism propensity

0.6260th %ile

GOF

0.6443th %ile

LOF

0.4037th %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

18 submitted variants in ClinVar

ClinVar

Classification Summary

VUS7

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	7	7
Likely Benign	1	1
Benign	0	0
Total	8	8

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap DNAAF8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →