DHX16

Chr 6

DEAH-box helicase 16

Also known as: DBP2, DDX16, NMOAS, PRO2014, PRP8, PRPF2, Prp2

NCBI Gene: 8449ENSG00000204560UniProt: O60231

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. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

Primary Disease Associations & Inheritance

UniProtNeuromuscular oculoauditory syndrome
213
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DHX16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 177 VUS of 213 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.000
Z-score 3.96
OE 0.47 (0.35–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.08Z-score
OE missense 0.66 (0.60–0.71)
417 obs / 635.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.35–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.60–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 31 / 65.6Missense obs/exp: 417 / 635.4Syn Z: 1.47

ClinVar Variant Classifications

213 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic6
VUS177
Likely Benign11
Benign10
Conflicting3
6
Pathogenic
6
Likely Pathogenic
177
VUS
11
Likely Benign
10
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
5
0
6
Likely Pathogenic
0
5
1
0
6
VUS
9
159
9
0
177
Likely Benign
0
2
3
6
11
Benign
0
7
0
3
10
Conflicting
—3
Total9174189213

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

View in ClinVar →

Protein Context — Lollipop Plot

DHX16 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DHX16-related intellectual disability, central nervous system anomalies and seizures

limited
ADUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare Case with Pathogenic Variant in DHX16 Gene Causing Neuromuscular Disease and Oculomotor Anomalies.
Kalampokini S et al.·Int J Mol Sci
2025Case report
Infantile onset encephalomyopathy, retinopathy, optic atrophy, and mitochondrial DNA depletion associated with a novel pathogenic DHX16 variant.
Hautakangas MR et al.·Clin Genet
2023
Expansion of the phenotypic spectrum associated with pathogenic missense variation in DHX16.
Drackley A et al.·Am J Med Genet A
2024Review
Heterozygous loss-of-function DHX9 variants are associated with neurodevelopmental disorders: Human genetic and experimental evidences.
Yamada M et al.·Eur J Med Genet
2023
Comprehensively analysis of splicing factors to construct prognosis prediction classifier in prostate cancer.
Zhang H et al.·J Cell Mol Med
2023
DHX16-Associated Neuromuscular Oculoauditory Syndrome: A Novel Case.
Clay S et al.·Am J Med Genet A
2025Case report
Paralog Studies Augment Gene Discovery: DDX and DHX Genes.
Paine I et al.·Am J Hum Genet
2019
Rare Variant Analysis and Molecular Dynamics Simulation in Alzheimer's Disease Identifies Exonic Variants in FLG.
Xiong W et al.·Genes (Basel)
2022
ZNF76 predicts prognosis and response to platinum chemotherapy in human ovarian cancer.
Hua T et al.·Biosci Rep
2021
Severe Macular Atrophy in an Infant With Neuromuscular Oculoauditory Syndrome.
Yun JS et al.·Ophthalmic Surg Lasers Imaging Retina
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools