DHX9

Chr 1AD

DExH-box helicase 9

Also known as: DDX9, LKP, MRD75, NDH2, NDHII, RHA

The DHX9 protein is an ATP-dependent helicase that unwinds double-stranded RNA and DNA-RNA complexes and functions as a transcriptional regulator involved in DNA replication, RNA processing, and gene expression. Mutations cause autosomal dominant intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.105), indicating that even heterozygous loss is likely to be pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical SummaryDHX9
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
44 unique Pathogenic / Likely Pathogenic· 123 VUS of 226 total submissions
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GeneReview available — DHX9
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 7.62
OE 0.04 (0.020.10)
Highly constrained

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

Missense Constraint
5.84Z-score
OE missense 0.38 (0.340.42)
264 obs / 698.6 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.04 (0.020.10)
00.351.4
Missense OE0.38 (0.340.42)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 3 / 73.6Missense obs/exp: 264 / 698.6Syn Z: -1.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateDHX9-related neurodevelopmental disorder and Charcot-Marie-Tooth diseaseLOFAD
DN
0.2897th %ile
GOF
0.3590th %ile
LOF
0.76top 10%

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

LOFprediction above median · 27% of P/LP variants are LoF · LOEUF 0.10

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

226 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic8
VUS123
Likely Benign16
Benign3
Conflicting1
36
Pathogenic
8
Likely Pathogenic
123
VUS
16
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
26
0
36
Likely Pathogenic
3
4
1
0
8
VUS
8
109
6
0
123
Likely Benign
0
4
2
10
16
Benign
0
0
1
2
3
Conflicting
1
Total201183612187

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

View in ClinVar →

Protein Context — Lollipop Plot

DHX9 · 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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