DDX23

Chr 12

DEAD-box helicase 23

Also known as: PRPF28, SNRNP100, U5-100K, U5-100KD, prp28

This gene encodes an RNA helicase that functions as a component of the U5 snRNP complex, facilitating pre-mRNA splicing and suppressing aberrant DNA:RNA hybrid structures (R-loops) during transcription. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, typically presenting in early childhood. The gene shows significant constraint against loss-of-function variants (LOEUF 0.361), indicating that complete loss of function is likely deleterious.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.36
Clinical SummaryDDX23
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.54) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.36LOEUF
pLI 0.542
Z-score 5.15
OE 0.22 (0.140.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
4.62Z-score
OE missense 0.43 (0.380.48)
218 obs / 512.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.22 (0.140.36)
00.351.4
Missense OE0.43 (0.380.48)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 11 / 50.5Missense obs/exp: 218 / 512.5Syn Z: 0.90
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateDDX23-related developmental disorderOTHERAD
DN
0.6745th %ile
GOF
0.5464th %ile
LOF
0.52top 25%

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DDX23 · 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

No active trials found for this gene.

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Clinical Literature
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