DDX23

Chr 12

DEAD-box helicase 23

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

NCBI Gene: 9416 ENSG00000174243 UniProt: Q9BUQ8 OMIM: 612172

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the DEAD box protein family. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a component of the U5 snRNP complex; it may facilitate conformational changes in the spliceosome during nuclear pre-mRNA splicing. An alternatively spliced transcript variant has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.36

Clinical Summary— DDX23

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

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

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 108 VUS of 147 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.36LOEUF

pLI 0.542

Z-score 5.15

OE 0.22 (0.14–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

4.62Z-score

OE missense 0.43 (0.38–0.48)

218 obs / 512.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.22 (0.14–0.36)

0≤0.351.4

Missense OE?0.43 (0.38–0.48)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 50.5Missense obs/exp: 218 / 512.5Syn Z: 0.90

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateDDX23-related developmental disorderOTHERAD

This gene — mechanism propensity

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

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS108

Likely Benign11

Benign1

Conflicting3

Pathogenic

Likely Pathogenic

108

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	0	3	0	0	3
VUS	9	98	1	0	108
Likely Benign	0	8	1	2	11
Benign	0	0	0	1	1
Conflicting	—				3
Total	9	111	2	3	128

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap DDX23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →