DHX8

Chr 17

DEAH-box helicase 8

Also known as: DDX8, Dhr2, HRH1, PRP22, PRPF22

NCBI Gene: 1659ENSG00000067596UniProt: Q14562

The encoded protein functions as an ATP-dependent RNA helicase that facilitates pre-mRNA splicing as a spliceosome component and releases spliced mRNAs from spliceosomes to enable their nuclear export. Mutations cause disease through a dominant-negative mechanism, as supported by the extremely low pLI score and low LOEUF indicating the gene is highly intolerant to loss-of-function variants. The specific disease phenotype and inheritance pattern associated with DHX8 mutations are not established in the provided data.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
4
Pubs (1 yr)
8
P/LP submissions
13%
P/LP missense
0.49
LOEUF
DN
Mechanism· predicted
Clinical Summary— DHX8
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 167 VUS of 237 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.49LOEUF
pLI 0.000
Z-score 4.89
OE 0.35 (0.25–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
5.03Z-score
OE missense 0.47 (0.43–0.52)
338 obs / 717.2 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.35 (0.25–0.49)
0≤0.351.4
Missense OE0.47 (0.43–0.52)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 23 / 65.8Missense obs/exp: 338 / 717.2Syn Z: 0.42
DN
0.7326th %ile
GOF
0.6052th %ile
LOF
0.3844th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

237 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS167
Likely Benign10
Benign13
7
Pathogenic
1
Likely Pathogenic
167
VUS
10
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
1
0
0
1
VUS
0
152
15
0
167
Likely Benign
0
3
3
4
10
Benign
0
3
10
0
13
Total0159354198

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

View in ClinVar →

Protein Context — Lollipop Plot

DHX8 · protein map & ClinVar variants

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

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 4 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