DAZ2

Summary

DAZ2 (deleted in azoospermia 2, HGNC:15964) is a protein-coding gene on chromosome Yq11.223, encoding Deleted in azoospermia protein 2 (Q13117). 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. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 57055 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Phenotypes (HPO): 9
• MANE Select transcript: NM_001389303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15964
Approved symbol	DAZ2
Name	deleted in azoospermia 2
Location	Yq11.223
Locus type	gene with protein product
Status	Approved
Aliases	pDP1678, MGC126442
Ensembl gene	ENSG00000205944
Ensembl biotype	protein_coding
OMIM	400026
Entrez	57055

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000382433, ENST00000382440, ENST00000382449

RefSeq mRNA: 7 — MANE Select: NM_001389303 NM_001005785, NM_001005786, NM_001388493, NM_001388494, NM_001388495, NM_001389303, NM_020363

CCDS: CCDS94719

Canonical transcript exons

ENST00000382440 — 28 exons

Exon	Start	End
ENSE00001592425	23229598	23229669
ENSE00001603036	23219533	23219743
ENSE00001605577	23243990	23244061
ENSE00001607297	23253541	23253612
ENSE00001622502	23280013	23280084
ENSE00001640624	23226344	23226490
ENSE00001659100	23272860	23272931
ENSE00001659494	23227905	23227968
ENSE00001659634	23285438	23285536
ENSE00001668820	23289500	23291356
ENSE00001674452	23248763	23248834
ENSE00001676137	23232041	23232112
ENSE00001682794	23239210	23239281
ENSE00001686143	23251145	23251216
ENSE00001689126	23226765	23226856
ENSE00001690453	23270476	23270547
ENSE00001695324	23280829	23280863
ENSE00001705999	23277628	23277699
ENSE00001706458	23268091	23268162
ENSE00001717191	23275244	23275315
ENSE00001723992	23228058	23228197
ENSE00001736653	23227417	23227468
ENSE00001736828	23246386	23246457
ENSE00001743603	23265707	23265778
ENSE00001748863	23234432	23234503
ENSE00001771158	23255918	23255989
ENSE00001780208	23236828	23236899
ENSE00001787726	23241606	23241677

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 84.10.

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	84.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.05	gold quality
right testis	UBERON:0004534	66.96	gold quality
testis	UBERON:0000473	63.97	gold quality
left testis	UBERON:0004533	62.87	gold quality
body of stomach	UBERON:0001161	49.96	gold quality
stomach	UBERON:0000945	47.25	gold quality
fundus of stomach	UBERON:0001160	44.08	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
right lobe of liver	UBERON:0001114	36.67	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
liver	UBERON:0002107	36.38	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
placenta	UBERON:0001987	35.70	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
duodenum	UBERON:0002114	32.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
calcaneal tendon	UBERON:0003701	31.99	gold quality
skin of abdomen	UBERON:0001416	31.89	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
zone of skin	UBERON:0000014	30.44	gold quality
urinary bladder	UBERON:0001255	30.03	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
skin of leg	UBERON:0001511	29.33	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
tonsil	UBERON:0002372	28.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting DAZ2, 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-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
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-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-9-3P	99.96	70.88	2068
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
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 8)

• DAZ gene copy number in severely idiopathic infertile men. Gene deletion of two copies of DAZ (DAZI and 2) was the cause of spermatogenic damage. (PMID:11883873)
• 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)
• There appears to be an asociation of DAZ1/DAZ2 deletion with spermatogenic impairment and male infertility in the South Chinese population. (PMID:23512232)
• Deletion of DAZ2 and DAZ4 gene copies is associated with male infertility. (PMID:24878370)
• 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)
• study reported a new type of AZFc deletion (gr/gr-DAZ2-DAZ4-CDY1b) and hypothesis that this new deletion is the result of 2 successive events favored by the unstable structure of AZFc region; also demonstrated that this deletion constitutes a relative high-risk factor for male infertility in Tunisian population (PMID:27457284)
• Direct reprogramming of human Sertoli cells into male germline stem cells with the self-renewal and differentiation potentials via overexpressing DAZL/DAZ2/BOULE genes. (PMID:34653405)

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), DAZ3 (ENSG00000187191), DAZ1 (ENSG00000188120), DAZ4 (ENSG00000205916)

Protein

Protein identifiers

Deleted in azoospermia protein 2 — Q13117 (reviewed: Q13117)

All UniProt accessions (2): E9PBY2, Q13117

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 (3)

UniProt ID	Names	Canonical?
Q13117-1	1	yes
Q13117-2	2
Q13117-3	3

RefSeq proteins (7): NP_001005785, NP_001005786, NP_001375422, NP_001375423, NP_001375424, NP_001376232, NP_065096 (=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 (26 total): domain 16, sequence conflict 4, compositionally biased region 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13117-F1	72.77	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): GOBP_SINGLE_FERTILIZATION, 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, GOBP_FERTILIZATION, CTCAAGA_MIR526B, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (5): spermatogenesis (GO:0007283), single fertilization (GO:0007338), cell differentiation (GO:0030154), positive regulation of translational initiation (GO:0045948), 3’-UTR-mediated mRNA stabilization (GO:0070935)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), translation activator activity (GO:0008494), nucleic acid binding (GO:0003676), 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
fertilization	1
cellular developmental process	1
translational initiation	1
regulation of translational initiation	1
mRNA stabilization	1
nucleic acid binding	1
mRNA binding	1
translation regulator activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

1381 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAZ2	CDY1	Q9Y6F8	943
DAZ2	CDY2A	Q9Y6F7	894
DAZ2	BPY2	O14599	892
DAZ2	USP9Y	O00507	758
DAZ2	PRY	O14603	754
DAZ2	DDX3Y	O15523	727
DAZ2	UTY	O14607	706
DAZ2	VCY	O14598	703
DAZ2	A6NGT6	A6NGT6	584
DAZ2	CDYL2	Q8N8U2	572
DAZ2	CDYL	Q9Y232	545
DAZ2	TSPY1	P09002	544
DAZ2	TMSB4Y	O14604	512
DAZ2	ZFY	P08048	509
DAZ2	DAZAP1	Q96EP5	488

IntAct

4 interactions, top by confidence:

A	B	Type	Score
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
DAZ2	CST4	psi-mi:“MI:0914”(association)	0.350
FUBP1	DAZ2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): DAZ2 (Two-hybrid), CCT8 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CST4 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), FAM136A (Affinity Capture-MS), ZG16B (Affinity Capture-MS), PUM2 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), OTUD4 (Affinity Capture-MS), DAZ2 (Affinity Capture-MS), CCT5 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CST2 (Affinity Capture-MS)

ESM2 similar proteins: A0A023PXQ4, A0A0U1RQI7, A6NJU9, A6NNC1, A8MRT5, A8MUU9, C9JG80, E2RYF6, E5RHQ5, F8W0I5, O13534, O59779, P08399, P0C732, P0C785, P0DTH6, P0DW28, P13208, P15941, P21787, P24856, P39564, P51861, P87269, Q00130, Q01456, Q12444, Q13117, Q1HVI8, Q27905, Q2EEQ3, Q4ZJY7, Q4ZJZ0, Q5SDL7, Q63661, Q69577, Q6B0Y1, Q6RY98, Q6ZQT0, Q6ZRX8

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

4252 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:23226342:A:AG	acceptor_gain	1.0000
Y:23226343:G:GG	acceptor_gain	1.0000
Y:23226426:GC:G	donor_gain	1.0000
Y:23226489:GG:G	donor_gain	1.0000
Y:23226490:GG:G	donor_gain	1.0000
Y:23226761:A:AG	acceptor_gain	1.0000
Y:23226763:A:AG	acceptor_gain	1.0000
Y:23226763:A:T	acceptor_loss	1.0000
Y:23226763:AGAT:A	acceptor_gain	1.0000
Y:23226763:AGATG:A	acceptor_gain	1.0000
Y:23226764:G:GA	acceptor_gain	1.0000
Y:23226764:GA:G	acceptor_gain	1.0000
Y:23226764:GAT:G	acceptor_gain	1.0000
Y:23226764:GATG:G	acceptor_gain	1.0000
Y:23226764:GATGG:G	acceptor_gain	1.0000
Y:23226852:AAAGG:A	donor_gain	1.0000
Y:23226853:AAGG:A	donor_gain	1.0000
Y:23226854:AGG:A	donor_gain	1.0000
Y:23226855:GG:G	donor_gain	1.0000
Y:23226855:GGG:G	donor_gain	1.0000
Y:23226856:GG:G	donor_gain	1.0000
Y:23226856:GGTG:G	donor_loss	1.0000
Y:23226857:G:GA	donor_loss	1.0000
Y:23226857:G:GG	donor_gain	1.0000
Y:23227415:A:AG	acceptor_gain	1.0000
Y:23227416:G:GG	acceptor_gain	1.0000
Y:23227416:GCT:G	acceptor_gain	1.0000
Y:23227416:GCTAT:G	acceptor_gain	1.0000
Y:23227466:GGA:G	donor_gain	1.0000
Y:23227467:GA:G	donor_gain	1.0000

AlphaMissense

4166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:23226467:T:C	F43L	0.999
Y:23226469:T:A	F43L	0.999
Y:23226469:T:G	F43L	0.999
Y:23227424:T:C	F84L	0.998
Y:23227426:T:A	F84L	0.998
Y:23227426:T:G	F84L	0.998
Y:23227428:T:A	V85D	0.998
Y:23226471:T:A	V44D	0.997
Y:23226465:T:A	V42D	0.996
Y:23227422:G:A	G83E	0.995
Y:23227425:T:C	F84S	0.994
Y:23227433:T:C	F87L	0.994
Y:23227435:T:A	F87L	0.994
Y:23227435:T:G	F87L	0.994
Y:23226468:T:C	F43S	0.993
Y:23227434:T:C	F87S	0.993
Y:23268156:T:A	N404K	0.992
Y:23268156:T:G	N404K	0.992
Y:23270541:T:A	N428K	0.992
Y:23270541:T:G	N428K	0.992
Y:23272925:T:A	N452K	0.992
Y:23272925:T:G	N452K	0.992
Y:23226468:T:G	F43C	0.989
Y:23226792:T:C	F60L	0.987
Y:23226794:T:A	F60L	0.987
Y:23226794:T:G	F60L	0.987
Y:23275309:T:A	N476K	0.984
Y:23275309:T:G	N476K	0.984
Y:23226793:T:C	F60S	0.983
Y:23227425:T:G	F84C	0.983

dbSNP variants (sampled 300 via entrez): RS112808539 (Y:23288018 A>C), RS113184890 (Y:23221430 A>C), RS1162528691 (Y:23229727 C>T), RS1167405373 (Y:23260023 T>C), RS1178755917 (Y:23224934 A>G), RS1179789910 (Y:23229637 A>G), RS1182615138 (Y:23257646 A>G), RS1207349407 (Y:23249637 G>T), RS1211578259 (Y:23223519 T>A), RS1212472725 (Y:23229618 T>C), RS12164463 (Y:23225042 G>A), RS1231657922 (Y:23229595 CA>C), RS1235625818 (Y:23249609 A>T), RS1239531701 (Y:23257065 A>C), RS1246664599 (Y:23235365 T>C)

Disease associations

OMIM: gene MIM:400026 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

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):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
manganese chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Manganese	decreases expression	1
Oxygen	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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