DNAAF4

Chr 15ADAR

dynein axonemal assembly factor 4

Also known as: CILD25, DYX1, DYX1C1, DYXC1, EKN1, RD, pf23

NCBI Gene: 161582 ENSG00000256061 UniProt: Q8WXU2 OMIM: 608706

This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Dyslexia, susceptibility to, 1}MIM #127700

Ciliary dyskinesia, primary, 25MIM #615482

UniProtDyslexia 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · primary ciliary dyskinesia 25 · AR · ClinGen 2024

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

1.11

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.000

Z-score 1.14

OE 0.74 (0.51–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.87Z-score

OE missense 1.17 (1.05–1.29)

251 obs / 215.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.51–1.11)

0≤0.351.4

Missense OE?1.17 (1.05–1.29)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 17 / 22.9Missense obs/exp: 251 / 215.2Syn Z: -1.35

Background carrier burden — how many people carry a rare variant somewhere in DNAAF4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

655 rare PASS variants

Rare truncating (LoF)

1 in 810

107 rare PASS variants

Rare synonymous (reference)

1 in 330

214 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAAF4. 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 140	1 in 920
South Asian	~43k	1 in 82	1 in 480
Remaining (unassigned)	~30k	1 in 110	1 in 680
European (Finnish)	~27k	1 in 300	1 in 1,200
Admixed American	~22k	1 in 85	1 in 1,400
African / African American	~21k	1 in 78	1 in 430
East Asian	~20k	1 in 74	1 in 580
Ashkenazi Jewish	~13k	1 in 650	1 in 1,300
Middle Eastern	~2,884	1 in 78	≈ 1 in 1,400

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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓