DDX31

Chr 9

DEAD-box helicase 31

Also known as: PPP1R25

NCBI Gene: 64794ENSG00000125485UniProt: Q9H8H2OMIM: 616533

DDX31 encodes a DEAD box RNA helicase that functions in ribosome biogenesis and p53 regulation through interaction with nucleophosmin (NPM1), and may also have DNA helicase activity. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, typically presenting in early childhood. The gene is highly intolerant to loss-of-function variants, indicating its essential role in cellular function.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.82
Clinical Summary— DDX31
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 145 VUS of 216 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.53
OE 0.59 (0.43–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.03Z-score
OE missense 1.00 (0.92–1.07)
478 obs / 480.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.43–0.82)
0≤0.351.4
Missense OE1.00 (0.92–1.07)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 26 / 44.2Missense obs/exp: 478 / 480.1Syn Z: -0.91
DN
0.80top 10%
GOF
0.6151th %ile
LOF
0.2968th %ile

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

216 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic1
VUS145
Likely Benign9
34
Pathogenic
1
Likely Pathogenic
145
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
1
0
1
VUS
0
110
35
0
145
Likely Benign
0
5
1
3
9
Benign
0
0
0
0
0
Total0115713189

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

View in ClinVar →

Protein Context — Lollipop Plot

DDX31 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients