DAZ3

Chr Y

deleted in azoospermia 3

Also known as: pDP1679

NCBI Gene: 57054 ENSG00000187191 UniProt: Q9NR90 OMIM: 400027

DAZ3 encodes an RNA-binding protein that regulates mRNA translation and plays an essential role in spermatogenesis, with expression restricted to premeiotic germ cells. Mutations cause azoospermia (absence of sperm) as part of the Y-chromosomal azoospermia factor, leading to male infertility. This gene is located on the Y chromosome and follows Y-linked inheritance, passing from father to son.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the DAZ gene family and is a candidate for the human Y-chromosomal azoospermia factor (AZF). Its expression is restricted to premeiotic germ cells, particularly in spermatogonia. It encodes an RNA-binding protein that is important for spermatogenesis. Four copies of this gene are found on chromosome Y within palindromic duplications; one pair of genes is part of the P2 palindrome and the second pair is part of the P1 palindrome. Each gene contains a 2.4 kb repeat including a 72-bp exon, called the DAZ repeat; the number of DAZ repeats is variable and there are several variations in the sequence of the DAZ repeat. Each copy of the gene also contains a 10.8 kb region that may be amplified; this region includes five exons that encode an RNA recognition motif (RRM) domain. This gene contains one copy of the 10.8 kb repeat. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— DAZ3

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Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.76top 25%

GOF

0.79top 25%

LOF

0.3549th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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.