DDX6

Chr 11

DEAD-box helicase 6

Also known as: HLR2, IDDILF, P54, RCK, Rck/p54

NCBI Gene: 1656 ENSG00000110367 UniProt: P26196

This protein is an RNA helicase that forms P-bodies for mRNA storage and degradation and is required for microRNA-induced gene silencing. Mutations cause autosomal dominant intellectual developmental disorder with impaired language and dysmorphic facies. The gene is highly constrained against loss-of-function variants (pLI 1.00), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the DEAD box protein family. The protein is an RNA helicase found in P-bodies and stress granules, and functions in translation suppression and mRNA degradation. It is required for microRNA-induced gene silencing. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Mar 2012]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with impaired language and dysmorphic facies

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in DDX6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

294 rare PASS variants

Rare truncating (LoF)

1 in 40,000

12 rare PASS variants

Rare synonymous (reference)

1 in 280

217 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DDX6. 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 350	1 in 55,000
South Asian	~43k	1 in 410	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,300	≈ 1 in 13,000
Admixed American	~22k	1 in 360	none seen
African / African American	~21k	1 in 380	none seen
East Asian	~20k	1 in 460	none seen
Ashkenazi Jewish	~13k	≈ 1 in 3,300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 480	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): 9 of 12 coding exons well covered in gnomAD exomes; exons 3, 10, 12 marginal. Genomes: all 12.? see exons ↓