DDX17

Chr 22

DEAD-box helicase 17

Also known as: P72, RH70

NCBI Gene: 10521 ENSG00000100201 UniProt: Q92841 OMIM: 608469

The DDX17 protein is an RNA helicase that unwinds RNA structures and regulates pre-mRNA splicing, microRNA processing, ribosomal RNA processing, and transcriptional activation of various genes involved in development and hormone signaling. Mutations in DDX17 cause autosomal dominant intellectual disability with distinctive facial features and developmental delays. This gene is extremely intolerant to loss-of-function variants (pLI 1.0, LOEUF 0.126), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

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 splicesosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an ATPase activated by a variety of RNA species, but not by dsDNA. This protein, and that encoded by DDX5 gene, are more closely related to each other than to any other member of the DEAD box family. This gene can encode multiple isoforms due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) start codon. [provided by RefSeq, Apr 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.13

Clinical Summary— DDX17

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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.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 16 VUS of 38 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 5.54

OE 0.03 (0.01–0.13)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.87Z-score

OE missense 0.47 (0.42–0.53)

202 obs / 427.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.13)

0≤0.351.4

Missense OE?0.47 (0.42–0.53)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 1 / 37.7Missense obs/exp: 202 / 427.3Syn Z: 0.06

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateDDX17-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

0.5180th %ile

GOF

0.4875th %ile

LOF

0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.13

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

38 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic2

VUS16

Likely Benign1

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	0	2	0	0	2
VUS	4	10	2	0	16
Likely Benign	0	1	0	0	1
Benign	0	0	0	1	1
Total	6	13	2	1	22

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap DDX17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →