DAZ1

Summary

DAZ1 (deleted in azoospermia 1, HGNC:2682) is a protein-coding gene on chromosome Yq11.223, encoding Deleted in azoospermia protein 1 (Q9NQZ3). 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 three copies of the 10.8 kb repeat. However, no transcripts containing three copies of the RRM domain have been described; thus the RefSeq for this gene contains only two RRM domains.

Source: NCBI Gene 1617 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 9
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004081

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2682
Approved symbol	DAZ1
Name	deleted in azoospermia 1
Location	Yq11.223
Locus type	gene with protein product
Status	Approved
Aliases	SPGY
Ensembl gene	ENSG00000188120
Ensembl biotype	protein_coding
OMIM	400003
Entrez	1617

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000405239, ENST00000426000, ENST00000466332, ENST00000540248

RefSeq mRNA: 2 — MANE Select: NM_004081 NM_001388496, NM_004081

CCDS: CCDS48209, CCDS94718

Canonical transcript exons

ENST00000405239 — 28 exons

Exon	Start	End
ENSE00001597343	23167185	23167256
ENSE00001598075	23169998	23170089
ENSE00001612801	23192052	23192198
ENSE00001614454	23140626	23140697
ENSE00001620467	23179497	23179636
ENSE00001622354	23169386	23169437
ENSE00001633941	23155174	23155245
ENSE00001644179	23180838	23180929
ENSE00001646624	23168657	23168796
ENSE00001646813	23180226	23180277
ENSE00001655036	23181204	23181350
ENSE00001675126	23152797	23152868
ENSE00001677573	23190574	23190637
ENSE00001692245	23190345	23190484
ENSE00001693241	23179726	23179789
ENSE00001695781	23168886	23168949
ENSE00001696683	23162349	23162420
ENSE00001697295	23143011	23143082
ENSE00001701677	23191074	23191125
ENSE00001707161	23164740	23164811
ENSE00001730215	23129355	23131211
ENSE00001742324	23159953	23160024
ENSE00001758855	23157570	23157641
ENSE00001793499	23170364	23170510
ENSE00001805705	23191686	23191777
ENSE00002288175	23198798	23199008
ENSE00003567366	23135175	23135273
ENSE00003674346	23139847	23139881

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 85.36.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.48	gold quality
right testis	UBERON:0004534	68.57	gold quality
testis	UBERON:0000473	65.74	gold quality
left testis	UBERON:0004533	63.76	gold quality
fundus of stomach	UBERON:0001160	61.86	gold quality
body of stomach	UBERON:0001161	61.02	gold quality
stomach	UBERON:0000945	58.83	gold quality
skin of abdomen	UBERON:0001416	51.69	gold quality
calcaneal tendon	UBERON:0003701	50.27	gold quality
zone of skin	UBERON:0000014	49.40	gold quality
skin of leg	UBERON:0001511	48.09	gold quality
right lobe of liver	UBERON:0001114	46.22	gold quality
ganglionic eminence	UBERON:0004023	45.07	gold quality
liver	UBERON:0002107	41.79	gold quality
skeletal muscle tissue	UBERON:0001134	39.90	gold quality
hypothalamus	UBERON:0001898	39.72	gold quality
apex of heart	UBERON:0002098	39.27	silver quality
duodenum	UBERON:0002114	38.59	gold quality
bone marrow cell	CL:0002092	38.10	gold quality
metanephros cortex	UBERON:0010533	37.80	gold 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
placenta	UBERON:0001987	36.37	silver quality
muscle tissue	UBERON:0002385	35.85	gold quality
monocyte	CL:0000576	35.42	gold quality
leukocyte	CL:0000738	35.17	gold quality
rectum	UBERON:0001052	35.15	silver quality
adult mammalian kidney	UBERON:0000082	34.87	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

Upstream regulators (CollecTRI, top): SRY

miRNA regulators (miRDB)

123 targeting DAZ1, 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-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-3065-5P	99.97	71.56	3281
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-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

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• role in male infertility - review (PMID:11688365)
• altered transcription in azoospermia (PMID:11869379)
• 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)
• Sertoli cell function is not damaged in patients with AZFc-DAZ deletions and that the strong reduction of germ cells does not affect the FSH-inhibin B feedback loop. (PMID:12039700)
• DAZ/DAZL protein can form a stable complex with human PUM2. (PMID:12511597)
• Loss of only some copies of DAZ is sufficient to lead to severe male infertility, but it is not a frequent finding in cryptorchid men. (PMID:15066457)
• Role in spermatogenesis. Decreased DAZ proteins in spermatogenic failure may be due to germ cell loss. Transcription of BOULE, DAZL, and DAZ not altered in degrees of spermatogenic failure. No increase of DAZL or BOULE found in DAZ deletion. (PMID:15066460)
• The deleted in azoospermia (DAZ) are believed to have important function in sperm production, since DAZ is frequently deleted in azoospermic and severy oligozoospermic men. (PMID:15253135)
• The frequency of partial copy deletion of DAZ gene in Chinese idiopathic azoospermia or severe oligozoospermia patients is much higher, suggesting that the deletion of DAZ1/DAZ2 may be one of the important factors of spermatogenesis damage. (PMID:15476166)
• DAZ activates translationally silent mRNAs during germ cell development through the direct recruitment of polyA-binding proteins. (PMID:16001084)
• Additional polymorphisms identified within the DAZ repeat regions of the DAZ genes indicate that sister chromatid exchange plays a significant role in the genesis of deletions, duplications, and polymorphisms of the Y chromosome. (PMID:16085382)
• DAZ genes are prone to deletions and duplications. Partial DAZ gene deletions are associated with oligozoospermia. (PMID:16275261)
• An association between DAZ haplotypes and Y chromosome haplogroups was found, and data show that the DAZ gene is not under selective constraints and its evolution depends only on the mutation rate. (PMID:16777954)
• The results showed that DAZ gene activity seems to correspond to the proliferative activity of stem cells of germinal epithelium. (PMID:16805138)
• DAZ cannot bind simultaneously to DAZAP1 and poly(A)-binding protein (PABP), and suggest that the phosphorylation-induced dissociation of DAZ and DAZAP1 may allow the former to stimulate translation by interacting with PABP. (PMID:16848763)
• complete DAZ deletion is a frequent genetic cause of severe oligozoospermia, and DAZ1/DAZ2 deletion is a high risk factor for the disease (PMID:16963411)
• AZFc subdeletions do not seem to cause severe impairment of spermatogenesis in Chilean men. (PMID:17416365)
• Quantitative real-time PCR assays of this protein gave positive predictive values of 78 per cent for the recovery of sperm from testicular biopsy. (PMID:17453684)
• The data show no relationship between ‘gr/gr’ AZC gene deletion and cryptorchidism. (PMID:17609244)
• Patients with complete Sertoli cell-only syndrome (SCOS) did not exhibit DAZ gene expression. (PMID:17881721)
• The expression of DAZ proteins in adult human testes is restricted to the spermatogonia and suggests a premeiotic role. (PMID:18385127)
• AZFc rearrangements/polymorphisms are transmitted to sons and may represent a risk factor for decreased testis function and male subfertility, which needs confirmation in further studies in larger cohorts (PMID:18440997)
• deletions of two DAZ gene copies are compatible with normal spermatogenesis and fertility. (PMID:18440997)
• PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes in the two Turner Syndrome patients having intact Y chromosome in >85% cells (PMID:19030103)
• All four DAZ genes are expressed in the human testis, and their products are highly polymorphic among men (PMID:19223287)
• human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes (PMID:19865085)
• The methylation patterns of CpG island (CGI) in the DAZ gene promoter region were different between somatic cells and spermatic cells (PMID:20170395)
• Report the prevalence of variations in the AZFc region of the human Y chromosome in infertile men. (PMID:23422238)
• There appears to be an asociation of DAZ1/DAZ2 deletion with spermatogenic impairment and male infertility in the South Chinese population. (PMID:23512232)
• genetic association studies in Han population in China: Data suggest that AZF1/DAZ1 duplications underlie genetic predisposition of Y-chromosome haplogroup K* to spermatogenic impairment (azoospermia/oligospermia) in the population studied. (PMID:23696539)
• genetic association study in Chinese population: Data suggest that combined patterns of copy number abnormality in DAZ1 (deleted in azoospermia 1) and/or BPY2 (basic charge Y-linked protein 2) are associated with spermatogenic impairment/azoospermia. (PMID:24935076)
• We did not found any statistically significant genetic association between DAZ alleles and idiopathic male infertility (PMID:25916124)
• Overexpression of DAZ1 is associated with breast tumors. (PMID:25994570)
• Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions. (PMID:26149076)
• 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)
• We investigated partial deletion of AZFc region and DAZ copy number in a population of Iranian infertile men and normozoospermic controls. (PMID:27739146)
• There was an increased frequency of DAZ microdeletion in blood samples from oligozoospermic and near azoospermic patients. A high frequency of DAZ microdeletion was observed in the sperm of patients with no DAZ microdeletion in their leukocytes compared to control. The results might be indicative of DAZ microdeletion induction during spermatogenesis. (PMID:28521575)
• Partial-AZFc deletions in Chilean men with primary spermatogenic impairment: gene dosage and Y-chromosome haplogroups. (PMID:33034826)
• Association of DAZL polymorphisms and DAZ deletion with male infertility: a systematic review and meta-analysis. (PMID:36434389)
• Y-chromosome haplogroups and Azoospermia Factor (AZF) analysis in Tunisian infertile male. (PMID:36591797)

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), DAZ4 (ENSG00000205916), DAZ2 (ENSG00000205944)

Protein

Protein identifiers

Deleted in azoospermia protein 1 — Q9NQZ3 (reviewed: Q9NQZ3)

All UniProt accessions (3): A0A0A0MSR9, A0A140VJH5, Q9NQZ3

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. Promotes germ-cell progression to meiosis and formation of haploid germ cells.

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. Expression restricted to premeiotic germ cells, particularly in spermatogonia (at protein level).

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. DAZ genes are prone to deletions but also to duplications. In a population of infertile men, DAZ genes deletions are associated with oligozoospermia but an increased number of DAZ genes is not a significant risk factor for spermatogenic failure. 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?
Q9NQZ3-1	1	yes
Q9NQZ3-2	2

RefSeq proteins (2): NP_001375425, NP_004072* (*=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 (25 total): domain 12, compositionally biased region 6, region of interest 3, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQZ3-F1	57.42	0.07

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, MITSIADES_RESPONSE_TO_APLIDIN_DN, 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, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, CTCAAGA_MIR526B, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS

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

1694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAZ1	PUM2	Q8TB72	968
DAZ1	DAZAP2	Q15038	960
DAZ1	CDY1	Q9Y6F8	956
DAZ1	CDY2A	Q9Y6F7	943
DAZ1	BPY2	O14599	930
DAZ1	DZIP1	Q86YF9	929
DAZ1	DAZAP1	Q96EP5	927
DAZ1	USP9Y	O00507	879
DAZ1	TSPY1	P09002	879
DAZ1	DDX3Y	O15523	865
DAZ1	PRY	O14603	848
DAZ1	UTY	O14607	795
DAZ1	DDX4	Q9NQI0	724
DAZ1	VCY	O14598	720
DAZ1	HSFY1	Q96LI6	707

IntAct

24 interactions, top by confidence:

A	B	Type	Score
DAZ1	DAZL	psi-mi:“MI:0915”(physical association)	0.570
DAZ1	BOLL	psi-mi:“MI:0915”(physical association)	0.550
DAZ1	DAZAP1	psi-mi:“MI:0915”(physical association)	0.510
DAZ1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.510
DAZAP1	DAZ1	psi-mi:“MI:0915”(physical association)	0.510
DAZAP2	DAZ1	psi-mi:“MI:0915”(physical association)	0.510
PUM2	DAZ1	psi-mi:“MI:0915”(physical association)	0.510
DAZ1	PUM2	psi-mi:“MI:0915”(physical association)	0.510
DAZ1	DAZ1	psi-mi:“MI:0915”(physical association)	0.400
	DAZ1	psi-mi:“MI:0915”(physical association)	0.400
Pum2	DAZ1	psi-mi:“MI:0915”(physical association)	0.400
DAZ1	Dazl	psi-mi:“MI:0915”(physical association)	0.370
DAZ1	DZIP1	psi-mi:“MI:0915”(physical association)	0.370
DAZ1	DZIP3	psi-mi:“MI:0915”(physical association)	0.370
QK3	DAZ1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (17): DAZ1 (Two-hybrid), DAZ1 (Reconstituted Complex), DAZ1 (Reconstituted Complex), DAZAP1 (Two-hybrid), DAZAP2 (Two-hybrid), DAZAP1 (Reconstituted Complex), DAZAP2 (Reconstituted Complex), DAZ1 (Reconstituted Complex), DAZL (Reconstituted Complex), PUM2 (Two-hybrid), QKI (Two-hybrid), BOLL (Two-hybrid), DZIP1 (Two-hybrid), DZIP1L (Two-hybrid), DZIP3 (Two-hybrid)

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

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

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

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
149291	GRCh38/hg38 Yq11.223-11.23(chrY:22727003-25749348)x0	Pathogenic
4526327	GRCh38/hg38 Yq11.223(chrY:23008278-23731504)x0	Likely pathogenic

SpliceAI

4661 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:23139882:C:CC	acceptor_gain	1.0000
Y:23139883:T:C	acceptor_gain	1.0000
Y:23139883:T:TC	acceptor_gain	1.0000
Y:23140697:CCTG:C	acceptor_loss	1.0000
Y:23140698:C:A	acceptor_loss	1.0000
Y:23140699:T:A	acceptor_loss	1.0000
Y:23140710:G:C	acceptor_gain	1.0000
Y:23162418:TGG:T	acceptor_gain	1.0000
Y:23165178:C:A	donor_gain	1.0000
Y:23167171:C:CA	donor_gain	1.0000
Y:23167640:T:TA	donor_gain	1.0000
Y:23167640:TCTAG:T	donor_gain	1.0000
Y:23168651:TCTTA:T	donor_loss	1.0000
Y:23168652:CTTA:C	donor_loss	1.0000
Y:23168653:TTA:T	donor_loss	1.0000
Y:23168654:TACC:T	donor_loss	1.0000
Y:23168655:A:AC	donor_gain	1.0000
Y:23168655:A:C	donor_loss	1.0000
Y:23168656:C:CC	donor_gain	1.0000
Y:23168656:C:CG	donor_loss	1.0000
Y:23168794:CAC:C	acceptor_gain	1.0000
Y:23168795:ACC:A	acceptor_loss	1.0000
Y:23168796:CCT:C	acceptor_loss	1.0000
Y:23168797:C:G	acceptor_loss	1.0000
Y:23168799:T:TC	acceptor_gain	1.0000
Y:23168800:T:C	acceptor_gain	1.0000
Y:23168801:T:C	acceptor_gain	1.0000
Y:23168801:T:TC	acceptor_gain	1.0000
Y:23168809:C:CT	acceptor_gain	1.0000
Y:23168810:A:T	acceptor_gain	1.0000

AlphaMissense

4784 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:23169426:A:T	V415D	0.998
Y:23169428:A:C	F414L	0.998
Y:23169428:A:T	F414L	0.998
Y:23169430:A:G	F414L	0.998
Y:23170385:A:C	F373L	0.998
Y:23170385:A:T	F373L	0.998
Y:23170387:A:G	F373L	0.998
Y:23180268:A:C	F249L	0.998
Y:23180268:A:T	F249L	0.998
Y:23180270:A:G	F249L	0.998
Y:23191114:A:T	V85D	0.998
Y:23191116:A:C	F84L	0.998
Y:23191116:A:T	F84L	0.998
Y:23191118:A:G	F84L	0.998
Y:23169419:A:C	F417L	0.997
Y:23169419:A:T	F417L	0.997
Y:23169421:A:G	F417L	0.997
Y:23192073:A:C	F43L	0.997
Y:23192073:A:T	F43L	0.997
Y:23192075:A:G	F43L	0.997
Y:23169420:A:G	F417S	0.996
Y:23170383:A:T	V374D	0.996
Y:23170389:A:T	V372D	0.996
Y:23181225:A:C	F208L	0.996
Y:23181225:A:T	F208L	0.996
Y:23181227:A:G	F208L	0.996
Y:23191107:A:C	F87L	0.996
Y:23191107:A:T	F87L	0.996
Y:23191109:A:G	F87L	0.996
Y:23169429:A:G	F414S	0.995

dbSNP variants (sampled 300 via entrez): RS111456076 (Y:23161205 G>T), RS111670989 (Y:23167997 C>T), RS113162688 (Y:23154448 T>A), RS1158895436 (Y:23166275 C>T), RS1162490488 (Y:23167165 C>T), RS1200901142 (Y:23163604 A>T), RS1204782459 (Y:23156646 C>A), RS1219929019 (Y:23156917 A>G), RS1267883001 (Y:23159050 A>C), RS1273341 (Y:23154441 T>C), RS1276743331 (Y:23155382 ATGAC>A), RS1286942323 (Y:23156683 A>G), RS1301731489 (Y:23166973 G>A), RS1302047113 (Y:23170950 A>C), RS1303970201 (Y:23188113 G>C)

Disease associations

OMIM: gene MIM:400003 | 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

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	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