Intellectual disability
Gene: DDX39B

DDX39B (DExD-box helicase 39B)
EnsemblGeneIds (GRCh38): ENSG00000198563
EnsemblGeneIds (GRCh37): ENSG00000198563
OMIM: 142560, Gene2Phenotype
DDX39B is in 1 panel

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence (four unrelated cases with missense variants) available for the association. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 10 Apr 2025, 6:18 p.m. | Last Modified: 10 Apr 2025, 6:18 p.m.

Panel Version: 8.238

As reviewed by Mike Spiller, PMID:39918047 reported the identification of monoallelic DDX39B variants in six patients from five unrelated families presenting with a neurodevelopmental disorder. Intellectual disability was reported in three of four unrelated patients identified with de novo missense variants, of which ID was severe in two and mild in one. The fourth patient had global developmental delay.

The two patients from the same family with splice variant did not present with ID.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.
Created: 10 Apr 2025, 12:31 p.m. | Last Modified: 10 Apr 2025, 6:16 p.m.

Panel Version: 8.237

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

39918047

Created: 10 Apr 2025, 11:32 a.m.
Last Modified: 10 Apr 2025, 6:16 p.m.
Panel version: 8.237

Mike Spiller (Sheffield Children's Hospital)

Green List (high evidence)

PMID: 39918047 - report 4 de novo missense variants in individuals with phenotypes of ID ranging from mild to severe (2 severe, 1 mild, 1 severity not stated but phenotype of GDD).
Hypotonia, short stature and skeletal abnormalities are also observed frequently.
Variants absent from gnomad, affect highly conserved amino acids in constrained regions of DEAD/DEAH box helicase domain.

Splice variant causing inframe deletion also identified in fifth family (proband and mother), but significance of this unclear as neither has ID.

Supported by functional studies:
Transcriptome profiling shows significant increase in abberant splicing events, consistent with DDX39B role as splicing factor.
Drosophila experiments - overexpression of WT human gene is lethal, but flies overexpressing variants were healthy, suggesting these variants cause loss of / reduced protein function.

Overall good evidence for DEAD box helicase missenses causing an autosomal dominant syndromic ID disorder.
Sources: Literature
Created: 20 Mar 2025, 9:35 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

PMID: 39918047

Created: 20 Mar 2025, 9:35 a.m.

Panel version: 8.163

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber

Phenotypes

neurodevelopmental disorder, MONDO:0700092
intellectual disability, MONDO:0001071

Tags

Q2_25_ promote_green Q2_25_ NHS_review

OMIM

142560

Clinvar variants

Variants in DDX39B

Penetrance

None

Publications

39918047

Panels with this gene

Intellectual disability