DDX39B

Chr 6

DExD-box helicase 39B

Also known as: BAT1, D6S81E, UAP56

NCBI Gene: 7919ENSG00000198563UniProt: Q13838

This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

42
ClinVar variants
7
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DDX39B
⚡
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.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 32 VUS of 42 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.22LOEUF
pLI 0.997
Z-score 4.12
OE 0.05 (0.01–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
4.56Z-score
OE missense 0.21 (0.17–0.26)
55 obs / 263.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.05 (0.01–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.21 (0.17–0.26)
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.0.82
0≤1.21.6
LoF obs/exp: 1 / 21.7Missense obs/exp: 55 / 263.5Syn Z: 1.38

ClinVar Variant Classifications

42 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS32
Benign3
4
Pathogenic
3
Likely Pathogenic
32
VUS
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
2
27
3
0
32
Likely Benign
0
0
0
0
0
Benign
0
0
2
1
3
Total22712142

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

View in ClinVar →

Protein Context — Lollipop Plot

DDX39B · 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
DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2.
Zhao G et al.·Signal Transduct Target Ther
2022
De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome.
Booth KTA et al.·Brain
2025
DDX39B K63-linked ubiquitination mediated by TRIM28 promotes NSCLC metastasis by enhancing ECAD lysosomal degradation.
Yuan H et al.·Signal Transduct Target Ther
2025
Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing.
Banerjee S et al.·Nucleic Acids Res
2024
RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma.
Tu Q et al.·J Exp Clin Cancer Res
2022
DDX39B Predicts Poor Survival and Associated with Clinical Benefit of Anti-PD-L1 Therapy in ccRCC.
Wei J et al.·Curr Cancer Drug Targets
2021
The RNA-binding protein DDX39B promotes colorectal adenocarcinoma progression by stabilizing DCLK1.
Liu S et al.·Hum Mol Genet
2025
DDX39B (BAT1), TNF and IL6 gene polymorphisms and association with clinical outcomes of patients with Plasmodium vivax malaria.
Mendonça VR et al.·Malar J
2014Cohort
The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.
Nakata D et al.·Biochem Biophys Res Commun
2017
Validation and functional follow-up of cervical cancer risk variants at the HLA locus.
Eisenblätter R et al.·HLA
2024Natural history
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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