DHX30

Chr 3AD

DExH-box helicase 30

Also known as: DDX30, NEDMIAL, RETCOR

NCBI Gene: 22907ENSG00000132153UniProt: Q7L2E3OMIM: 616423

DHX30 encodes an RNA-dependent helicase that plays an important role in mitochondrial large ribosomal subunit assembly and associates with mitochondrial DNA. Mutations cause neurodevelopmental disorder with variable motor and speech impairment through autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.115), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.121 OMIM phenotype
Clinical Summary— DHX30
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with severe motor impairment and absent language · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 204 VUS of 339 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 6.62
OE 0.04 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
5.30Z-score
OE missense 0.46 (0.42–0.50)
352 obs / 763.9 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.04 (0.01–0.12)
0≤0.351.4
Missense OE0.46 (0.42–0.50)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 2 / 55.0Missense obs/exp: 352 / 763.9Syn Z: -1.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDHX30-related neurodevelopmental disorderOTHERAD
DN
0.3495th %ile
GOF
0.3689th %ile
LOF
0.67top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 27% of P/LP variants are LoF · LOEUF 0.12
GOF1 literature citation

Literature Evidence

GOFDHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation.PMID:34020708

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

ClinVar Variant Classifications

339 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic10
VUS204
Likely Benign76
Benign3
Conflicting9
16
Pathogenic
10
Likely Pathogenic
204
VUS
76
Likely Benign
3
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
7
6
0
16
Likely Pathogenic
4
4
2
0
10
VUS
9
179
15
1
204
Likely Benign
0
31
5
40
76
Benign
0
0
1
2
3
Conflicting
—9
Total162212943318

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

View in ClinVar →

Protein Context — Lollipop Plot

DHX30 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients