DHX34

Chr 19

DExH-box helicase 34

Also known as: DDX34

NCBI Gene: 9704 ENSG00000134815 OMIM: 615475

DHX34 encodes an ATP-binding RNA helicase that is required for nonsense-mediated decay, a cellular quality control mechanism that degrades mRNA transcripts containing premature stop codons. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and brain malformations. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.768).

OMIM ResearchSummary from RefSeq, UniProt

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. It is mapped to the glioma 19q tumor suppressor region and is a tumor suppressor candidate gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.77

Clinical Summary— DHX34

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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

3 unique Pathogenic / Likely Pathogenic· 251 VUS of 335 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.88

OE 0.56 (0.41–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.08Z-score

OE missense 1.01 (0.95–1.07)

750 obs / 743.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.56 (0.41–0.77)

0≤0.351.4

Missense OE?1.01 (0.95–1.07)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 28 / 50.0Missense obs/exp: 750 / 743.5Syn Z: -1.44

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedDHX34-related intellectual disabilityOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6259th %ile

GOF

0.5366th %ile

LOF

0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

335 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS251

Likely Benign26

Benign29

Conflicting1

Pathogenic

Likely Pathogenic

251

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	1	1	0	0	2
VUS	3	248	0	0	251
Likely Benign	0	17	2	7	26
Benign	0	12	4	13	29
Conflicting	—				1
Total	4	279	6	20	310

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap DHX34 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →