DDX3Y

Chr Y

DEAD-box helicase 3 Y-linked

Also known as: DBY

NCBI Gene: 8653 ENSG00000067048 UniProt: O15523 OMIM: 400010

The protein is an ATP-dependent RNA helicase that is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.29) and may enhance interferon-beta expression during immune responses. Mutations cause male infertility with reduced germ cell numbers and Sertoli-cell only syndrome. This gene follows Y-linked inheritance, being located on the Y chromosome and therefore passed from father to son.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the DEAD-box RNA helicase family, characterized by nine conserved motifs, included the conserved Asp-Glu-Ala-Asp (DEAD) motif. These motifs are thought to be involved in ATP binding, hydrolysis, RNA binding, and in the formation of intramolecular interactions. This protein shares high similarity to DDX3X, on the X chromosome, but a deletion of this gene is not complemented by DDX3X. Mutations in this gene result in male infertility, a reduction in germ cell numbers, and can result in Sertoli-cell only sydrome. Pseudogenes sharing similarity to both this gene and the DDX3X paralog are found on chromosome 4 and the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 0.29

Clinical Summary— DDX3Y

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic of 50 total submissions

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GeneReview available — DDX3Y

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.965

Z-score 2.99

OE 0.00 (0.00–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.10Z-score

OE missense 0.45 (0.36–0.57)

53 obs / 117.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.29)

0≤0.351.4

Missense OE?0.45 (0.36–0.57)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 0 / 10.4Missense obs/exp: 53 / 117.0Syn Z: 0.96

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic4

Likely Benign2

Likely Pathogenic

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	4	0	4
VUS	0	0	0
Likely Benign	0	2	2
Benign	0	0	0
Total	4	2	6

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

View in ClinVar →

63 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap DDX3Y — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →