DAZ3

Summary

DAZ3 (deleted in azoospermia 3, HGNC:15965) is a protein-coding gene on chromosome Yq11.23, encoding Deleted in azoospermia protein 3 (Q9NR90). RNA-binding protein that plays an essential role in spermatogenesis.

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.

Source: NCBI Gene 57054 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total — 1 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_020364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15965
Approved symbol	DAZ3
Name	deleted in azoospermia 3
Location	Yq11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187191
Ensembl biotype	protein_coding
OMIM	400027
Entrez	57054

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000315357, ENST00000382365, ENST00000446723, ENST00000691059, ENST00000692367

RefSeq mRNA: 1 — MANE Select: NM_020364 NM_020364

CCDS: CCDS35489

Canonical transcript exons

ENST00000382365 — 19 exons

Exon	Start	End
ENSE00001594431	24786514	24786585
ENSE00001602566	24805457	24805508
ENSE00001604640	24774350	24774421
ENSE00001618455	24796027	24796098
ENSE00001620779	24784137	24784208
ENSE00001655608	24791271	24791342
ENSE00001684201	24788894	24788965
ENSE00001695979	24813183	24813393
ENSE00001706721	24804728	24804867
ENSE00001709286	24804957	24805020
ENSE00001715045	24768899	24768997
ENSE00001722493	24803256	24803327
ENSE00001728003	24793650	24793721
ENSE00001733013	24806069	24806160
ENSE00001757238	24800813	24800884
ENSE00001785551	24798423	24798494
ENSE00001799005	24773570	24773604
ENSE00001803162	24806435	24806581
ENSE00001879735	24763069	24764925

Expression profiles

Bgee: expression breadth tissue_specific, 6 present calls, max score 85.49.

Top tissues by expression

129 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.49	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
placenta	UBERON:0001987	31.72	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
fundus of stomach	UBERON:0001160	27.09	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.88	gold quality
urinary bladder	UBERON:0001255	26.66	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
stomach	UBERON:0000945	25.22	gold quality
muscle of leg	UBERON:0001383	25.06	gold quality
leukocyte	CL:0000738	24.80	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
monocyte	CL:0000576	24.52	gold quality
body of stomach	UBERON:0001161	24.51	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting DAZ3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3617-3P	99.98	67.86	918
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4302	99.89	67.94	1187

Literature-anchored findings (GeneRIF, showing 4)

• a common variant of the human Y chromosome lacks the DAZ3/DAZ4 and BPY2.2/BPY2.3 doublets in distal AZFc and thus these genes cannot be required for male fertility (PMID:14639527)
• AZFc subdeletions do not seem to cause severe impairment of spermatogenesis in Chilean men. (PMID:17416365)
• All four DAZ genes are expressed in the human testis, and their products are highly polymorphic among men (PMID:19223287)
• Studies indicate that partial RNA-binding proteins DAZ1/2 deletion was associated wih male infertility, but partial RNA-binding proteins DAZ3/4 deletion was not associated with male infertility. (PMID:26232607)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dazl	ENSDARG00000036214
drosophila_melanogaster	bol	FBGN0011206
caenorhabditis_elegans		WBGENE00000935

Paralogs (5): DAZL (ENSG00000092345), BOLL (ENSG00000152430), DAZ1 (ENSG00000188120), DAZ4 (ENSG00000205916), DAZ2 (ENSG00000205944)

Protein

Protein identifiers

Deleted in azoospermia protein 3 — Q9NR90 (reviewed: Q9NR90)

All UniProt accessions (3): E7ERQ6, E7ETR3, Q9NR90

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that plays an essential role in spermatogenesis. May act by binding to the 3’-UTR of mRNAs and regulating their translation.

Subunit / interactions. Forms a heterodimer with BOLL and DAZL. Interacts with PUM2, DAZAP1, DAZAP2, DZIP1 and DZIP3.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Testis specific.

Disease relevance. Spermatogenic failure Y-linked 2 (SPGFY2) [MIM:415000] A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. The disease may be caused by variants affecting the gene represented in this entry. AZFc deletions in the Yq11.23 region including the DAZ genes are the most common known genetic cause of human male infertility.

Domain organisation. The DAZ domains are essential and mediate the interaction with DAZAP1 and DAZAP2.

Polymorphism. The number as well as the precise structure of the DAZ proteins probably differs within the population.

Miscellaneous. The DAZ proteins (DAZ, DAZ2, DAZ4 and DAZ4) are all encoded by a strongly repeated region of the Y chromosome, in two clusters each comprising an inverted pair of DAZ genes. They are very similar, which gives their indidual characterization difficult. Thus, most experiments do not discriminate between the different members. One can therefore suppose that reported interactions with a DAZ protein involve all the 4 proteins.

Similarity. Belongs to the RRM DAZ family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR90-1	1	yes
Q9NR90-2	2

RefSeq proteins (1): NP_065097* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR037551	DAZ_RRM_vert	Domain
IPR043628	DAZ_dom	Domain

Pfam: PF00076, PF18872

UniProt features (18 total): domain 13, compositionally biased region 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR90-F1	61.94	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, GOBP_MALE_GAMETE_GENERATION, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, CTCAAGA_MIR526B, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TRANSLATION, GOBP_REGULATION_OF_TRANSLATION

GO Biological Process (4): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), positive regulation of translational initiation (GO:0045948), 3’-UTR-mediated mRNA stabilization (GO:0070935)

GO Molecular Function (5): mRNA 3’-UTR binding (GO:0003730), translation activator activity (GO:0008494), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of translation	2
binding	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
translational initiation	1
regulation of translational initiation	1
mRNA stabilization	1
mRNA binding	1
translation regulator activity	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DAZ3	CFTR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): DAZ3 (PCA)

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0U1RQI7, A6NJU9, A6NKU9, A6NNC1, A8MRT5, B2SU53, B9G9L9, C6UYI3, C9JG80, E5RHQ5, F8W0I5, O04492, O60732, P02895, P06916, P07907, P0DJ88, P0DJ89, P0DKL2, P0DPF3, P13208, P14417, P20465, P21733, P32072, Q06602, Q13117, Q27905, Q3BBV0, Q4ZJY7, Q4ZJZ0, Q5TAG4, Q5TI25, Q6P3W6, Q6RY98, Q6ZQT0, Q7T3L1, Q86SG3

Diamond homologs: A0A2R8Y4L2, A2A5N3, A3LXL0, A5A6H4, A6NDE4, A6NEQ0, A7VJC2, D3Z4I3, F4HT49, M0R7T6, O43347, O57437, O88569, P04256, P07909, P09651, P09867, P0C7P1, P0CB38, P0DJD3, P0DJD4, P11940, P17130, P20965, P21187, P21522, P22626, P29341, P42731, P48809, P49312, P51989, P51990, P51992, P60047, P61286, Q00916, Q02926, Q10422, Q13117

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
870522	GRCh37/hg19 Yq11.223-11.23(chrY:24651462-28328263)x0	Pathogenic

SpliceAI

2985 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:24773605:C:CC	acceptor_gain	1.0000
Y:24773606:T:C	acceptor_gain	1.0000
Y:24773606:T:TC	acceptor_gain	1.0000
Y:24774434:G:C	acceptor_gain	1.0000
Y:24798492:TGG:T	acceptor_gain	1.0000
Y:24801251:C:A	donor_gain	1.0000
Y:24803242:C:CA	donor_gain	1.0000
Y:24803711:T:TA	donor_gain	1.0000
Y:24803711:TCTAG:T	donor_gain	1.0000
Y:24804722:TCTTA:T	donor_loss	1.0000
Y:24804723:CTTA:C	donor_loss	1.0000
Y:24804724:TTAC:T	donor_loss	1.0000
Y:24804725:TACCT:T	donor_loss	1.0000
Y:24804726:A:AC	donor_gain	1.0000
Y:24804727:C:CA	donor_loss	1.0000
Y:24804727:C:CC	donor_gain	1.0000
Y:24804865:CAC:C	acceptor_gain	1.0000
Y:24804868:C:CA	acceptor_loss	1.0000
Y:24804869:T:A	acceptor_loss	1.0000
Y:24804870:T:C	acceptor_gain	1.0000
Y:24804870:T:TC	acceptor_gain	1.0000
Y:24804871:T:C	acceptor_gain	1.0000
Y:24804872:T:C	acceptor_gain	1.0000
Y:24804872:T:TC	acceptor_gain	1.0000
Y:24804880:C:CT	acceptor_gain	1.0000
Y:24804881:A:T	acceptor_gain	1.0000
Y:24804956:CATAA:C	donor_gain	1.0000
Y:24804960:A:C	donor_gain	1.0000
Y:24805455:A:AC	donor_gain	1.0000
Y:24805455:ACT:A	donor_gain	1.0000

AlphaMissense

2796 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1022210 (Y:24810683 A>T), RS111228173 (Y:24780388 C>G), RS111288938 (Y:24798186 C>A), RS111329313 (Y:24781314 C>T), RS111420235 (Y:24778529 T>C), RS111528515 (Y:24804926 T>C), RS111787178 (Y:24776007 G>T), RS111884710 (Y:24779316 G>A), RS111967704 (Y:24778720 T>A), RS112196577 (Y:24779295 T>G), RS112275220 (Y:24768153 T>C), RS112381832 (Y:24778990 G>T), RS112419106 (Y:24778979 G>C), RS112519782 (Y:24799714 A>G), RS112520434 (Y:24778644 G>A)

Disease associations

OMIM: gene MIM:400027 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000798	Oligozoospermia
HP:0001450	Y-linked inheritance
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Volatile Organic Compounds	affects expression	1

Clinical trials (associated diseases)

125 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia