DAZ2

Chr Y

deleted in azoospermia 2

Also known as: pDP1678

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.

Summary from RefSeq, UniProt
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Primary Disease Associations & Inheritance

UniProtSpermatogenic failure Y-linked 2
0
Active trials
1
Pubs (1 yr)
77
P/LP submissions
P/LP missense
1.89
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryDAZ2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
77 unique Pathogenic / Likely Pathogenic· 14 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.288
Z-score 0.25
OE 0.00 (0.001.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.17Z-score
OE missense 1.61 (0.321.92)
1 obs / 0.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.001.89)
00.351.4
Missense OE1.61 (0.321.92)
00.61.4
Synonymous OE0.00
01.21.6
LoF obs/exp: 0 / 0.1Missense obs/exp: 1 / 0.6Syn Z: 0.34
DN
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.

ClinVar Variant Classifications

103 submitted variants in ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic2
VUS14
Likely Benign9
Benign3
75
Pathogenic
2
Likely Pathogenic
14
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
75
Likely Pathogenic
2
VUS
14
Likely Benign
9
Benign
3
Total103

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DAZ2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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