DHX40

Chr 17

DEAH-box helicase 40

Also known as: ARG147, DDX40, PAD

NCBI Gene: 79665UniProt: Q8IX18

This gene encodes a member of the DExH/D box family of ATP-dependent RNA helicases that have an essential role in RNA metabolism. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 17.[provided by RefSeq, Oct 2009]

0
Active trials
83
ClinVar variants
13
Pathogenic / LP
3.0
Missense Z
0.36
LOEUF
2
Pubs (2 yr)
Clinical Summary— DHX40
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 68 VUS of 83 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.36LOEUF
pLI 0.756
Z-score 4.67
OE 0.20 (0.12–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.02Z-score
OE missense 0.56 (0.50–0.63)
209 obs / 373.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.12–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.56 (0.50–0.63)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 8 / 39.8Missense obs/exp: 209 / 373.0Syn Z: 0.62

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS68
Likely Benign1
Benign1
11
Pathogenic
2
Likely Pathogenic
68
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
2
0
2
VUS
0
61
7
0
68
Likely Benign
0
1
0
0
1
Benign
0
0
0
1
1
Total06220183

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

View in ClinVar →

Protein Context — Lollipop Plot

DHX40 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Identification of DHX40 as a candidate susceptibility gene for colorectal and hematological neoplasia
Olkinuora A et al.·Leukemia
2023
CRISPR/Cas9-Mediated Knockout of tnfaip1 in Zebrafish Plays a Role in Early Development
Huang S et al.·Genes (Basel)
2023Functional
DNA methylome profiling identifies novel methylated genes in epithelial ovarian cancer patients with platinum resistance.
Hua T et al.·J Obstet Gynaecol Res
2021Cohort
Overview of Gene Special Issue "Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis"
Giampietro PF et al.·Genes (Basel)
2022Review
An introduction to new robust linear and monotonic correlation coefficients
Tabatabai M et al.·BMC Bioinformatics
2021
USP7 substrates identified by proteomics analysis reveal the specificity of USP7
Nie L et al.·Genes Dev
2022
A gene signature associated with alpha-linolenic acid metabolism predicts clinical prognosis in hepatocellular carcinoma
Shi Q et al.·Eur J Med Res
2026
A Rare Case Report of 17q23.1q23.2 Microdeletion With Homozygosity of 11p11.2q13.4 in a Newborn
Barola S et al.·Cureus
2022Case report
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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