DDX3Y

Summary

DDX3Y (DEAD-box helicase 3 Y-linked, HGNC:2699) is a protein-coding gene on chromosome Yq11.221, encoding ATP-dependent RNA helicase DDX3Y (O15523). Probable ATP-dependent RNA helicase.

The protein encoded by this gene is a member of the DEAD-box RNA helicase family, characterized by nine conserved motifs, included the conserved Asp-Glu-Ala-Asp (DEAD) motif. These motifs are thought to be involved in ATP binding, hydrolysis, RNA binding, and in the formation of intramolecular interactions. This protein shares high similarity to DDX3X, on the X chromosome, but a deletion of this gene is not complemented by DDX3X. Mutations in this gene result in male infertility, a reduction in germ cell numbers, and can result in Sertoli-cell only sydrome. Pseudogenes sharing similarity to both this gene and the DDX3X paralog are found on chromosome 4 and the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 8653 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 57 total — 3 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_004660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2699
Approved symbol	DDX3Y
Name	DEAD-box helicase 3 Y-linked
Location	Yq11.221
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000067048
Ensembl biotype	protein_coding
OMIM	400010
Entrez	8653

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000336079, ENST00000360160, ENST00000440554, ENST00000454054, ENST00000463199, ENST00000469101, ENST00000472510, ENST00000493363, ENST00000495478, ENST00000894516, ENST00000894517, ENST00000894518, ENST00000894519, ENST00000894520, ENST00000894521, ENST00000939915, ENST00000939916

RefSeq mRNA: 4 — MANE Select: NM_004660 NM_001122665, NM_001302552, NM_001324195, NM_004660

CCDS: CCDS14782

Canonical transcript exons

ENST00000336079 — 17 exons

Exon	Start	End
ENSE00000773386	12916261	12916442
ENSE00000773388	12915630	12915774
ENSE00000773394	12912727	12912882
ENSE00000862006	12911839	12911968
ENSE00001352037	12918043	12920478
ENSE00001605860	12909360	12909407
ENSE00001614446	12914884	12914982
ENSE00001703401	12916517	12916634
ENSE00001722940	12917403	12917542
ENSE00001729063	12916907	12917060
ENSE00001746396	12915067	12915227
ENSE00001832940	12904868	12904981
ENSE00003463722	12907537	12907594
ENSE00003534942	12915883	12916027
ENSE00003574309	12912963	12913062
ENSE00003789826	12913718	12913853
ENSE00003791575	12914564	12914649

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.9575 / max 2346.9690, expressed in 923 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201162	23.4590	906
201161	14.8352	885
201165	0.5168	203
201163	0.0695	33
201164	0.0564	20
201160	0.0206	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.69	gold quality
male germ cell	CL:0000015	98.22	gold quality
endothelial cell	CL:0000115	97.84	gold quality
cauda epididymis	UBERON:0004360	97.13	gold quality
upper leg skin	UBERON:0004262	96.50	gold quality
right lung	UBERON:0002167	96.41	gold quality
right testis	UBERON:0004534	96.41	gold quality
left testis	UBERON:0004533	96.32	gold quality
caput epididymis	UBERON:0004358	96.31	gold quality
seminal vesicle	UBERON:0000998	96.00	gold quality
testis	UBERON:0000473	95.93	gold quality
blood vessel layer	UBERON:0004797	95.75	gold quality
corpus epididymis	UBERON:0004359	95.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.96	gold quality
trabecular bone tissue	UBERON:0002483	94.79	gold quality
rectum	UBERON:0001052	94.66	gold quality
prostate gland	UBERON:0002367	94.47	gold quality
metanephros cortex	UBERON:0010533	94.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.23	gold quality
cerebellar vermis	UBERON:0004720	94.06	gold quality
mucosa of urinary bladder	UBERON:0001259	93.31	gold quality
tendon of biceps brachii	UBERON:0008188	93.25	gold quality
urethra	UBERON:0000057	93.23	gold quality
parietal pleura	UBERON:0002400	91.80	gold quality
cartilage tissue	UBERON:0002418	91.51	gold quality
penis	UBERON:0000989	90.33	gold quality
synovial joint	UBERON:0002217	90.32	gold quality
pleura	UBERON:0000977	90.07	gold quality
middle frontal gyrus	UBERON:0002702	89.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	19.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

189 targeting DDX3Y, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834

Literature-anchored findings (GeneRIF, showing 21)

• Gene structure of the human DDX3 and chromosome mapping of its related sequences.Its organization was the same as that of the human DBY gene, a closely related sequence present on the Y chromosome. (PMID:11710523)
• graft-versus-host (GVH) disease after HLA-identical stem cell transplantation is the result of recognition of minor histocompatibility antigens (mHags) by immunocompetent T lymphocytes from recipient origin. (PMID:11929796)
• coordinated B and T cell immune response to H-Y minor histocompatibility antigen, DBY, after allogeneic transplant (PMID:15096539)
• Human Y- and X-encoded DEAD box RNA helicase proteins DDX3Y and DDX3X are interchangeable and have an essential function. Ddx3x mRNA was expressed in almost every cell in mouse testis, suggesting that Ddx3x is involved in spermatogenesis (PMID:15383328)
• The finding that the testicular transcript of DDX3Y is significantly decreased in patients with severe spermatogenenic failure, especially in those presenting maturation arrest, suggests an important role of DDX3Y during spermatogenesis. (PMID:17881721)
• Expression of DDX3Y is detected in all myeloid and lymphoid leukemic cells that carry an intact Y chromosome. (PMID:18299450)
• We show here the development of a coordinated B and T-cell response to DBY in a recipient of sex mismatched allogeneic hematopoietic stem-cell transplantation. (PMID:21709606)
• fetal germ cell DDX3Y protein expression suggests a role in early spermatogonial proliferation (PMID:22466863)
• DLG1, XIST, DDX3Y and RPS4Y1 genes can classify samples into different group clearly, and they are regarded as high confidence distinct gene biomarkers of Parkinson disease. (PMID:25275262)
• results suggest that MSY genes may play an important role in neural differentiation and demonstrate that DDX3Y could play a multifunctional role in neural cell development (PMID:26144214)
• DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs. (PMID:26456624)
• a significant nsSNP in DBY was identified through computational approaches; this deleterious mutation may interfere with spermatogenesis (PMID:29520635)
• intercellular antigen transfer of DBY is tightly regulated via binding to HSC70 and that this mechanism influences recognition and rejection of MHC-II-negative tumors in vivo. (PMID:31205025)
• MicroRNA-497 functions as an inflammatory suppressor via targeting DDX3Y and modulating toll-like receptor 4/NF-kappaB in cigarette smoke extract-stimulated human bronchial epithelial cells. (PMID:31696986)
• Sex matters: XIST and DDX3Y gene expression as a tool to determine fetal sex in human first trimester placenta. (PMID:32792067)
• Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. (PMID:34437837)
• Sexually dimorphic RNA helicases DDX3X and DDX3Y differentially regulate RNA metabolism through phase separation. (PMID:35588748)
• AZFa Y gene, DDX3Y, evolved novel testis transcript variants in primates with proximal 3 UTR polyadenylation for germ cell specific translation. (PMID:35624115)
• DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia. (PMID:36997603)
• Antibody-mediated pathogenesis of chronic GVHD through DBY/HLA class II complexes and induction of a GVL effect. (PMID:37363859)
• Antioncogenic roles of USP9Y and DDX3Y in lung cancer: USP9Y stabilizes DDX3Y by preventing its degradation through deubiquitination. (PMID:38217953)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddx3xb	ENSDARG00000005774
danio_rerio	ddx3xa	ENSDARG00000020573
mus_musculus	Ddx3y	ENSMUSG00000069045
rattus_norvegicus	Ddx3y	ENSRNOG00000057231

Paralogs (38): DDX20 (ENSG00000064703), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), DDX18 (ENSG00000088205), DDX24 (ENSG00000089737), DDX17 (ENSG00000100201), DDX49 (ENSG00000105671), DDX50 (ENSG00000107625), DDX5 (ENSG00000108654), DDX25 (ENSG00000109832), DDX6 (ENSG00000110367), DDX55 (ENSG00000111364), DDX59 (ENSG00000118197), DDX54 (ENSG00000123064), DDX39A (ENSG00000123136), DDX27 (ENSG00000124228), DDX31 (ENSG00000125485), DDX56 (ENSG00000136271), EIF4A3 (ENSG00000141543), DDX46 (ENSG00000145833), DDX4 (ENSG00000152670), EIF4A2 (ENSG00000156976), DDX19B (ENSG00000157349), EIF4A1 (ENSG00000161960), DDX21 (ENSG00000165732), DDX19A (ENSG00000168872), TDRD12 (ENSG00000173809), DDX23 (ENSG00000174243), DDX10 (ENSG00000178105), DDX28 (ENSG00000182810), DDX41 (ENSG00000183258), DDX53 (ENSG00000184735), DDX51 (ENSG00000185163), DDX42 (ENSG00000198231), DDX39B (ENSG00000198563), DDX47 (ENSG00000213782), DDX3X (ENSG00000215301), DDX52 (ENSG00000278053)

Protein

Protein identifiers

ATP-dependent RNA helicase DDX3Y — O15523 (reviewed: O15523)

Alternative names: DEAD box protein 3, Y-chromosomal

All UniProt accessions (3): O15523, C9J081, C9J8G5

UniProt curated annotations — full annotation on UniProt →

Function. Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed at the mRNA level, with highest levels in testis. Testis-specific (at protein level). Expressed predominantly in spermatogonia, but occasionally detected in some pre-leptotene/leptotene spermatocytes.

Disease relevance. Located in the ‘azoospermia factor a’ (AZFa) region on chromosome Y which is deleted in Sertoli cell-only syndrome. This is an infertility disorder in which no germ cells are visible in seminiferous tubules leading to azoospermia.

Similarity. Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O15523-1	1	yes
O15523-2	2
O15523-3	3

RefSeq proteins (4): NP_001116137, NP_001289481, NP_001311124, NP_004651* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000629	RNA-helicase_DEAD-box_CS	Conserved_site
IPR001650	Helicase_C-like	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014014	RNA_helicase_DEAD_Q_motif	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00270, PF00271

Enzyme classification (BRENDA):

• EC 3.6.4.13 — RNA helicase (BRENDA: 3 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (39 total): modified residue 16, compositionally biased region 6, splice variant 3, sequence conflict 3, binding site 2, domain 2, region of interest 2, short sequence motif 2, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15523-F1	72.91	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 198–205; 222–229

Post-translational modifications (17): 2, 55, 85, 89, 100, 101, 103, 109, 129, 181, 454, 590, 592, 603, 615, 630, 213

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 253 (showing top): GGGACCA_MIR133A_MIR133B, MODULE_52, MCLACHLAN_DENTAL_CARIES_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, MODULE_151, MODULE_45, AAGCCAT_MIR135A_MIR135B, BOYLAN_MULTIPLE_MYELOMA_D_DN, ATGTTAA_MIR302C, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, MODULE_66, GTGCCTT_MIR506, MODULE_118, CAGCAGG_MIR370

GO Biological Process (3): gamete generation (GO:0007276), negative regulation of gene expression (GO:0010629), cell differentiation (GO:0030154)

GO Molecular Function (11): DNA binding (GO:0003677), RNA helicase activity (GO:0003724), mRNA binding (GO:0003729), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), membrane (GO:0016020), P granule (GO:0043186), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleic acid binding	2
ATP-dependent activity	2
binding	2
sexual reproduction	1
multicellular organismal reproductive process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cellular developmental process	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
RNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
germ plasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2995 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDX3Y	USP9Y	O00507	985
DDX3Y	UTY	O14607	982
DDX3Y	KDM5D	Q9BY66	981
DDX3Y	EIF1AY	O14602	889
DDX3Y	ZFY	P08048	876
DDX3Y	TMSB4Y	O14604	865
DDX3Y	DAZ1	Q9NQZ3	865
DDX3Y	RBMY1A1	P0DJD3	827
DDX3Y	RPS4Y1	P22090	816
DDX3Y	PPP1CC	P36873	815
DDX3Y	BPY2	O14599	799
DDX3Y	TOP1	P11387	767
DDX3Y	CDY1	Q9Y6F8	765
DDX3Y	SRY	Q05066	730
DDX3Y	DAZ2	Q13117	727

IntAct

67 interactions, top by confidence:

A	B	Type	Score
NUDCD2	DDX3Y	psi-mi:“MI:0915”(physical association)	0.590
ESR1		psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
DDX3Y		psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	DDX3Y	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
PAK4	SNRPE	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
ORF7	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
ATG4B	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
LGALS9B	ABCC4	psi-mi:“MI:0914”(association)	0.350
CRYBG2	DDX3Y	psi-mi:“MI:0914”(association)	0.350
ZC3H11A	DDX3Y	psi-mi:“MI:0914”(association)	0.350
CLDN3	DDX3Y	psi-mi:“MI:0914”(association)	0.350
TIMP3	DDX3Y	psi-mi:“MI:0914”(association)	0.350
VPS35	DDX3Y	psi-mi:“MI:0914”(association)	0.350
ESRRG	DDX3Y	psi-mi:“MI:0914”(association)	0.350

BioGRID (132): CCNB2 (Co-fractionation), DDX3Y (Proximity Label-MS), DDX3Y (Proximity Label-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS), DDX3Y (Affinity Capture-MS)

ESM2 similar proteins: A1CH78, A1CXK7, A2QI25, A3LQ01, A4RHF1, A5DQS0, A5DZE6, A6R3L3, A6SEH9, A6ZP47, A6ZWD3, A7EJY3, A7TKR8, C8V8H4, D0PV95, O00571, O13370, O15523, P06634, P0CQ74, P0CQ75, P16381, P24346, P24784, Q0CLJ6, Q1DJF0, Q2HBE7, Q2UGK3, Q4I7K4, Q4JG17, Q4P733, Q4WP13, Q5A4E2, Q5RF43, Q62095, Q62167, Q6BU54, Q6CB69, Q6CLR3, Q6FP38

Diamond homologs: A1C6C4, A1CH78, A1CXK7, A1DGZ7, A2QC74, A2QI25, A3LQ01, A3LQW7, A4QSS5, A4RHF1, A5DL80, A5DQS0, A5DS77, A5DZE6, A6R3L3, A6RGE3, A6SEH9, A6SFW7, A6ZP47, A6ZRX0, A6ZWD3, A7E449, A7EJY3, A7TKR8, C8V8H4, D0PV95, G0SFM2, O00571, O01836, O13370, O15523, P06634, P09052, P0CQ74, P0CQ75, P0CQ76, P0CQ77, P16381, P19109, P24346

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Processing of Capped Intron-Containing Pre-mRNA	6	12.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	3
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
443056	GRCh37/hg19 Yq11.21-11.221(chrY:14844481-16824498)x0	Pathogenic
816433	GRCh37/hg19 Yq11.21(chrY:14486671-15098073)x0	Pathogenic
870525	GRCh37/hg19 Yq11.21-11.221(chrY:14443478-15230544)x0	Pathogenic
155537	GRCh38/hg38 Yq11.21-11.221(chrY:12322751-13118630)x0	Likely pathogenic
2429751	NM_004660.5(DDX3Y):c.428dup (p.Glu145fs)	Likely pathogenic
2429752	NM_004660.5(DDX3Y):c.1230_1231del (p.Asn412fs)	Likely pathogenic
2429753	NM_004660.5(DDX3Y):c.1272dup (p.Lys425Ter)	Likely pathogenic
2429754	NM_004660.5(DDX3Y):c.1609+1del	Likely pathogenic

SpliceAI

2617 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:12907535:A:AG	acceptor_gain	1.0000
Y:12907536:G:GG	acceptor_gain	1.0000
Y:12907536:GCTT:G	acceptor_gain	1.0000
Y:12907590:GAGCA:G	donor_gain	1.0000
Y:12907591:AGCA:A	donor_gain	1.0000
Y:12907592:GCA:G	donor_gain	1.0000
Y:12907592:GCAG:G	donor_gain	1.0000
Y:12907595:G:GG	donor_gain	1.0000
Y:12909358:A:AG	acceptor_gain	1.0000
Y:12909358:AGAAG:A	acceptor_gain	1.0000
Y:12909359:G:GA	acceptor_gain	1.0000
Y:12909359:GAA:G	acceptor_gain	1.0000
Y:12909359:GAAGG:G	acceptor_gain	1.0000
Y:12909407:GGT:G	donor_loss	1.0000
Y:12909409:T:G	donor_loss	1.0000
Y:12910233:A:T	donor_gain	1.0000
Y:12910301:G:GT	donor_gain	1.0000
Y:12910301:G:T	donor_gain	1.0000
Y:12911832:A:AG	acceptor_gain	1.0000
Y:12911832:ATT:A	acceptor_gain	1.0000
Y:12911834:T:A	acceptor_gain	1.0000
Y:12911835:GAA:G	acceptor_loss	1.0000
Y:12911836:AAGG:A	acceptor_loss	1.0000
Y:12911837:A:AG	acceptor_gain	1.0000
Y:12911837:A:AT	acceptor_loss	1.0000
Y:12911838:G:GG	acceptor_gain	1.0000
Y:12911838:G:GT	acceptor_loss	1.0000
Y:12911924:A:T	donor_gain	1.0000
Y:12911950:G:GT	donor_gain	1.0000
Y:12911965:G:GT	donor_gain	1.0000

AlphaMissense

4343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:12913795:A:C	Q205H	1.000
Y:12913795:A:T	Q205H	1.000
Y:12913802:G:C	A208P	1.000
Y:12913803:C:A	A208D	1.000
Y:12913836:T:A	M219K	1.000
Y:12913836:T:C	M219T	1.000
Y:12913836:T:G	M219R	1.000
Y:12913838:G:C	A220P	1.000
Y:12913839:C:A	A220D	1.000
Y:12913841:T:C	C221R	1.000
Y:12913842:G:A	C221Y	1.000
Y:12913843:T:G	C221W	1.000
Y:12913845:C:A	A222D	1.000
Y:12914564:G:A	G225E	1.000
Y:12914569:G:A	G227R	1.000
Y:12914569:G:C	G227R	1.000
Y:12914569:G:T	G227W	1.000
Y:12914570:G:A	G227E	1.000
Y:12914570:G:T	G227V	1.000
Y:12914572:A:C	K228Q	1.000
Y:12914581:G:C	A231P	1.000
Y:12914582:C:A	A231E	1.000
Y:12914584:T:C	F232L	1.000
Y:12914586:T:A	F232L	1.000
Y:12914586:T:G	F232L	1.000
Y:12914588:T:C	L233P	1.000
Y:12914927:T:G	L268W	1.000
Y:12914930:T:A	V269D	1.000
Y:12914936:C:A	A271D	1.000
Y:12914938:C:A	P272T	1.000

dbSNP variants (sampled 300 via entrez): RS1000822330 (Y:12902522 C>A), RS1001249661 (Y:12918794 G>C), RS1001741722 (Y:12920311 T>C), RS1002744552 (Y:12911658 A>G), RS1003594315 (Y:12910568 A>G), RS1004653953 (Y:12920467 A>G), RS1005613217 (Y:12905614 T>C), RS1006973188 (Y:12904408 G>T), RS1008455282 (Y:12914163 A>G), RS1012137744 (Y:12918512 A>G), RS1012815229 (Y:12902656 A>G), RS1014564042 (Y:12920543 T>G), RS1015237550 (Y:12919158 C>G,T), RS1017323921 (Y:12912157 A>T), RS1017915009 (Y:12905916 C>T)

Disease associations

OMIM: gene MIM:400010 | 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

1 associations (top):

Study	Trait	p-value
GCST010733_3	Autism	2.000000e-08

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

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
cobaltous chloride	increases expression	2
Vehicle Emissions	increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases methylation, increases expression	1
afimoxifene	decreases expression	1
sodium arsenite	affects methylation	1
tetrabromobisphenol A	increases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
chromium hexavalent ion	increases abundance, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
bromovanin	increases expression	1
bisphenol S	increases expression	1
incobotulinumtoxinA	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	decreases expression	1
Acetaminophen	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D6SS	WAe001-A-2F	Embryonic stem cell	Male

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