DAZ2

Chr Y

deleted in azoospermia 2

Also known as: pDP1678

NCBI Gene: 57055 ENSG00000205944 UniProt: Q13117 OMIM: 400026

The protein is an RNA-binding protein that regulates mRNA translation and plays an essential role in spermatogenesis, with expression restricted to premeiotic germ cells. Mutations cause male infertility due to azoospermia (absence of sperm), as this gene is a candidate for the Y-chromosomal azoospermia factor. The 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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.89

Clinical Summary— DAZ2

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.288

Z-score 0.25

OE 0.00 (0.00–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.17Z-score

OE missense 1.61 (0.32–1.92)

1 obs / 0.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.89)

0≤0.351.4

Missense OE?1.61 (0.32–1.92)

0≤0.61.4

Synonymous OE?0.00

0≤1.21.6

LoF obs/exp: 0 / 0.1Missense obs/exp: 1 / 0.6Syn Z: 0.34

This gene — mechanism propensity

0.7325th %ile

GOF

0.78top 25%

LOF

0.4331th %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.