DDX6

Chr 11AD

DEAD-box helicase 6

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

NCBI Gene: 1656 ENSG00000110367 UniProt: P26196 OMIM: 600326

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.171 OMIM phenotype

Clinical Summary— DDX6

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.65

OE 0.04 (0.01–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.78Z-score

OE missense 0.34 (0.29–0.41)

89 obs / 260.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.34 (0.29–0.41)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 1 / 27.2Missense obs/exp: 89 / 260.8Syn Z: 0.24

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongDDX6-related intellectual disabilityOTHERAD

This gene — mechanism propensity

0.4785th %ile

GOF

0.4579th %ile

LOF

0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.