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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DDX3Y
DEAD-box helicase 3 Y-linked
Chromosome Y Β· Yq11.221
NCBI Gene: 8653Ensembl: ENSG00000067048.18HGNC: HGNC:2699UniProt: O15523
97PubMed Papers
20Diseases
0Drugs
4Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcytosolmembranegamete generationazoospermiaamyotrophic lateral sclerosisataxia telangiectasiabreast carcinoma
✦AI Summary

DDX3Y is a Y-linked DEAD-box RNA helicase that exhibits distinct biochemical properties from its X-linked homolog DDX3X. The protein functions as an ATP-dependent RNA helicase with weaker ATPase activity compared to DDX3X, contributing to slower disassembly dynamics of DDX3Y-containing ribonucleoprotein condensates 1. DDX3Y forms nanometer-scale RNA-protein clusters through its intrinsically disordered N-terminal region, which are critical for its catalytic activity and RNA unwinding function 2. Expression is tightly regulated through post-transcriptional cross-regulation with DDX3X, where increased DDX3Y levels lead to decreased DDX3X transcripts via mRNA destabilization, maintaining balanced total protein levels 3. In sheep, DDX3Y shows high testicular expression that increases during development, with genetic variants affecting expression levels correlating with testis size 4. Despite being located in the AZFa region associated with male infertility, mouse studies demonstrate that DDX3Y is dispensable for spermatogenesis when other paralogs are present 5. The gene exhibits complex transcriptional control in human testis with tissue-specific promoters, including a primate-specific distal promoter containing Y-specific minisatellite sequences that evolved to provide germline-specific expression control 6.

Sources cited
1
DDX3Y has weaker ATPase activity than DDX3X and forms condensates with slower disassembly dynamics
PMID: 35588748
2
DDX3Y forms nanometer-scale RNA-protein clusters through its N-terminal intrinsically disordered region that support catalytic activity
PMID: 39591970
3
DDX3Y and DDX3X exhibit post-transcriptional cross-regulation through mRNA destabilization to maintain balanced protein levels
PMID: 39794123
4
DDX3Y shows high testicular expression in sheep with genetic variants affecting expression correlating with testis size
PMID: 34963194
5
DDX3Y is dispensable for spermatogenesis in mice when other paralogs are present
PMID: 30613052
6
DDX3Y has complex transcriptional control with primate-specific promoters containing Y-specific minisatellite sequences for testis-specific expression
PMID: 20374305
Disease Associationsβ“˜20
azoospermiaOpen Targets
0.39Weak
amyotrophic lateral sclerosisOpen Targets
0.07Suggestive
ataxia telangiectasiaOpen Targets
0.06Suggestive
breast carcinomaOpen Targets
0.05Suggestive
multiple sclerosisOpen Targets
0.05Suggestive
Adams-Oliver syndromeOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
cystic fibrosisOpen Targets
0.02Suggestive
male infertilityOpen Targets
0.02Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
spina bifidaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
gonadoblastomaOpen Targets
0.01Suggestive
small cell osteogenic sarcomaOpen Targets
0.01Suggestive
infertilityOpen Targets
0.01Suggestive
in situ carcinomaOpen Targets
0.01Suggestive
disorder of sexual differentiationOpen Targets
0.01Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
Burkitts lymphomaOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.01Suggestive
Pathogenic Variants4
NM_004660.5(DDX3Y):c.428dup (p.Glu145fs)Likely pathogenic
Non-obstructive azoospermia
β˜…β˜†β˜†β˜†2023β†’ Residue 145
NM_004660.5(DDX3Y):c.1230_1231del (p.Asn412fs)Likely pathogenic
Non-obstructive azoospermia
β˜…β˜†β˜†β˜†2023β†’ Residue 412
NM_004660.5(DDX3Y):c.1272dup (p.Lys425Ter)Likely pathogenic
Non-obstructive azoospermia
β˜…β˜†β˜†β˜†2023β†’ Residue 425
NM_004660.5(DDX3Y):c.1609+1delLikely pathogenic
Non-obstructive azoospermia
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
SRYProtein interaction97%UTYProtein interaction97%ZFYProtein interaction97%KDM5DProtein interaction97%USP9YProtein interaction97%EIF1AYProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
20%
Liver
19%
Ovary
0%
Brain
0%
Heart
0%
Gene Interaction Network
Click a node to explore
DDX3YSRYUTYZFYKDM5DUSP9YEIF1AY
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O15523
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.42Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.13 [0.05–0.42]
RankingsWhere DDX3Y stands among ~20K protein-coding genes
  • #4,931of 20,598
    Most Researched97 Β· top quartile
  • #3,749of 5,498
    Most Pathogenic Variants4
  • #2,202of 17,882
    Most Constrained (LOEUF)0.42 Β· top quartile
Genes detectedDDX3Y
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Sexually dimorphic RNA helicases DDX3X and DDX3Y differentially regulate RNA metabolism through phase separation.
PMID: 35588748
Mol Cell Β· 2022
1.00
2
Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases
PMID: 39794123
Genome Res Β· 2025
0.90
3
Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases
PMID: 39026797
bioRxiv Β· 2024
0.80
4
RNA helicases DDX3X and DDX3Y form nanometer-scale RNA-protein clusters that support catalytic activity.
PMID: 39591970
Curr Biol Β· 2024
0.70
5
A mutation modulating DDX3Y gene expression cosegregates with the major Y-chromosomal haplogroups and with testis size in Hu sheep.
PMID: 34963194
Anim Genet Β· 2022
0.60