DDX25
geneOn this page
Also known as GRTH
Summary
DDX25 (DEAD-box helicase 25, HGNC:18698) is a protein-coding gene on chromosome 11q24.2, encoding ATP-dependent RNA helicase DDX25 (Q9UHL0). ATP-dependent RNA helicase.
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The encoded protein is a gonadotropin-regulated and developmentally expressed testicular RNA helicase. It may serve to maintain testicular functions related to steroidogenesis and spermatogenesis.
Source: NCBI Gene 29118 — RefSeq curated summary.
At a glance
- Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
- GWAS associations: 3
- Clinical variants (ClinVar): 106 total — 1 pathogenic
- MANE Select transcript:
NM_013264
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:18698 |
| Approved symbol | DDX25 |
| Name | DEAD-box helicase 25 |
| Location | 11q24.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | GRTH |
| Ensembl gene | ENSG00000109832 |
| Ensembl biotype | protein_coding |
| OMIM | 607663 |
| Entrez | 29118 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 8 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined
ENST00000263576, ENST00000525943, ENST00000526875, ENST00000530129, ENST00000530414, ENST00000530834, ENST00000531000, ENST00000532928, ENST00000584970, ENST00000637851, ENST00000910614, ENST00000927046, ENST00000942563
RefSeq mRNA: 2 — MANE Select: NM_013264
NM_001330438, NM_013264
CCDS: CCDS44766, CCDS81646
Canonical transcript exons
ENST00000263576 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000994957 | 125904508 | 125904580 |
| ENSE00002732679 | 125922820 | 125928843 |
| ENSE00003554090 | 125908196 | 125908288 |
| ENSE00003598506 | 125908401 | 125908503 |
| ENSE00003599461 | 125911311 | 125911488 |
| ENSE00003605805 | 125921191 | 125921379 |
| ENSE00003624134 | 125917014 | 125917251 |
| ENSE00003627286 | 125918628 | 125918790 |
| ENSE00003635663 | 125906074 | 125906209 |
| ENSE00003637001 | 125905553 | 125905597 |
| ENSE00003637057 | 125905212 | 125905278 |
| ENSE00003661276 | 125910364 | 125910478 |
Expression profiles
Bgee: expression breadth ubiquitous, 191 present calls, max score 96.41.
FANTOM5 (CAGE): breadth broad, TPM avg 2.4102 / max 159.6841, expressed in 283 samples.
FANTOM5 promoters (4 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 117484 | 2.1944 | 279 |
| 117482 | 0.1369 | 75 |
| 117481 | 0.0668 | 47 |
| 117483 | 0.0120 | 5 |
Top tissues by expression
280 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| left testis | UBERON:0004533 | 96.41 | gold quality |
| right testis | UBERON:0004534 | 96.37 | gold quality |
| adult organism | UBERON:0007023 | 95.27 | gold quality |
| testis | UBERON:0000473 | 93.80 | gold quality |
| sperm | CL:0000019 | 92.24 | gold quality |
| cortical plate | UBERON:0005343 | 91.66 | gold quality |
| right frontal lobe | UBERON:0002810 | 91.32 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 91.24 | gold quality |
| male germ cell | CL:0000015 | 90.99 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 90.78 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 90.70 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 90.62 | gold quality |
| cerebellar cortex | UBERON:0002129 | 90.46 | gold quality |
| prefrontal cortex | UBERON:0000451 | 90.34 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 90.10 | gold quality |
| nucleus accumbens | UBERON:0001882 | 89.94 | gold quality |
| caudate nucleus | UBERON:0001873 | 89.85 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 89.54 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 89.48 | gold quality |
| cingulate cortex | UBERON:0003027 | 89.45 | gold quality |
| frontal cortex | UBERON:0001870 | 89.42 | gold quality |
| neocortex | UBERON:0001950 | 89.19 | gold quality |
| cerebellum | UBERON:0002037 | 88.98 | gold quality |
| putamen | UBERON:0001874 | 88.49 | gold quality |
| pituitary gland | UBERON:0000007 | 88.38 | gold quality |
| cerebral cortex | UBERON:0000956 | 88.27 | gold quality |
| adenohypophysis | UBERON:0002196 | 88.25 | gold quality |
| telencephalon | UBERON:0001893 | 87.83 | gold quality |
| hypothalamus | UBERON:0001898 | 87.76 | gold quality |
| forebrain | UBERON:0001890 | 87.67 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 4.34 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
6 targeting DDX25, 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-4776-3P | 100.00 | 68.73 | 1340 |
| HSA-MIR-4729 | 99.69 | 72.18 | 4233 |
| HSA-MIR-7844-5P | 99.55 | 68.56 | 1428 |
| HSA-MIR-542-3P | 99.34 | 67.58 | 1270 |
| HSA-MIR-4724-3P | 97.57 | 67.31 | 785 |
| HSA-MIR-7109-3P | 94.23 | 67.19 | 743 |
Literature-anchored findings (GeneRIF, showing 7)
- SNP IVS6+55G–>T and c.852C–>T of GRTH gene may be associated with male infertility with azoospermia or severe oligozoospermia. (PMID:16293649)
- Data show that the Arg(242)His missense mutation of the GRTH/DDX25 gene associated with expression of a protein with reduced basicity, and the absence of the phospho-GRTH species, could impact on germ cell development and/or function. (PMID:17848414)
- The association of GRTH mutations with male infertility underlines the importance of GRTH as a central, post-transcriptional regulator of spermatogenesis. (PMID:17889551)
- multifunctional RNA helicase that is an essential regulator of spermatogenesis (PMID:19875492)
- Analysed the association of GRTH gene IVS6+55G/T and c.852C/T polymorphisms with male infertility. The c.852 T allele was associated with an increased risk of male infertility (OR: 3.16, P = 0.008), whereas IVS6+55G/T allele conferred no risk. (PMID:24168058)
- Targeted knock-in mice with a human mutation in GRTH/DDX25 reveals the essential role of phosphorylated GRTH in spermatid development during spermatogenesis. (PMID:31009948)
- Characterization of the Phosphorylation Site of GRTH/DDX25 and Protein Kinase A Binding Interface Provides Structural Basis for the Design of a Non-Hormonal Male Contraceptive. (PMID:31040297)
Cross-species orthologs
2 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Ddx25 | ENSMUSG00000032101 |
| rattus_norvegicus | Ddx25 | ENSRNOG00000012260 |
Paralogs (38): DDX20 (ENSG00000064703), DDX3Y (ENSG00000067048), DDX1 (ENSG00000079785), DDX43 (ENSG00000080007), DDX18 (ENSG00000088205), DDX24 (ENSG00000089737), DDX17 (ENSG00000100201), DDX49 (ENSG00000105671), DDX50 (ENSG00000107625), DDX5 (ENSG00000108654), 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 DDX25 — Q9UHL0 (reviewed: Q9UHL0)
Alternative names: DEAD box protein 25, Gonadotropin-regulated testicular RNA helicase
All UniProt accessions (7): Q9UHL0, A0A1B0GV69, A0A384NYS3, E9PR46, H0YD26, J3QL17, J3QRJ6
UniProt curated annotations — full annotation on UniProt →
Function. ATP-dependent RNA helicase. Required for mRNA export and translation regulation during spermatid development.
Subcellular location. Cytoplasm. Nucleus.
Tissue specificity. Highly expressed in the Leydig and germ cells of the testis and weakly expressed in the pituitary and hypothalamus.
Post-translational modifications. Phosphorylated on threonine residues. The phosphorylated form is found in the cytoplasm but not in the nucleus.
Induction. Up-regulated at transcriptional level by chorionic gonadotropin via cyclic AMP-induced androgen formation in the Leydig cell.
Similarity. Belongs to the DEAD box helicase family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9UHL0-1 | 1 | yes |
| Q9UHL0-2 | 2 |
RefSeq proteins (2): NP_001317367, NP_037396* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| 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 (26 total): strand 7, helix 6, short sequence motif 4, domain 2, sequence conflict 2, turn 2, chain 1, binding site 1, splice variant 1
Structure
Experimental structures (PDB)
1 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 2RB4 | X-RAY DIFFRACTION | 2.8 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9UHL0-F1 | 81.15 | 0.48 |
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 (1): 143–150
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 96 (showing top):
BENPORATH_ES_WITH_H3K27ME3, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, AACYNNNNTTCCS_UNKNOWN, GOBP_MALE_GAMETE_GENERATION, GOBP_TRANSLATION, GOBP_NUCLEAR_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, MODULE_206, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, LIAO_METASTASIS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GNF2_CCNA1, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION
GO Biological Process (7): mRNA export from nucleus (GO:0006406), regulation of translation (GO:0006417), spermatid development (GO:0007286), poly(A)+ mRNA export from nucleus (GO:0016973), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), mRNA transport (GO:0051028)
GO Molecular Function (10): 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 (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytoplasmic stress granule (GO:0010494), chromatoid body (GO:0033391)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| ATP-dependent activity | 2 |
| binding | 2 |
| cytoplasmic ribonucleoprotein granule | 2 |
| RNA export from nucleus | 1 |
| gene expression | 1 |
| mRNA transport | 1 |
| translation | 1 |
| post-transcriptional regulation of gene expression | 1 |
| regulation of protein metabolic process | 1 |
| germ cell development | 1 |
| spermatid differentiation | 1 |
| mRNA export from nucleus | 1 |
| developmental process involved in reproduction | 1 |
| male gamete generation | 1 |
| cellular developmental process | 1 |
| RNA transport | 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 binding | 1 |
| nucleic acid conformation isomerase activity | 1 |
| catalytic activity, acting on a nucleic acid | 1 |
| catalytic activity | 1 |
| intracellular membrane-bounded organelle | 1 |
| intracellular anatomical structure | 1 |
| cellular anatomical structure | 1 |
Protein interactions and networks
STRING
936 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| DDX25 | HYLS1 | Q96M11 | 943 |
| DDX25 | PKNOX2 | Q96KN3 | 903 |
| DDX25 | TDRD6 | O60522 | 715 |
| DDX25 | TDRD7 | Q8NHU6 | 672 |
| DDX25 | TNP2 | Q05952 | 550 |
| DDX25 | PIWIL2 | Q8TC59 | 514 |
| DDX25 | PRM2 | P04554 | 507 |
| DDX25 | CPAP | Q9HC77 | 495 |
| DDX25 | TSSK6 | Q9BXA6 | 492 |
| DDX25 | TDRD1 | Q9BXT4 | 489 |
| DDX25 | NANOS1 | Q8WY41 | 470 |
| DDX25 | PIWIL1 | Q96J94 | 465 |
| DDX25 | MAN2B2 | Q9Y2E5 | 449 |
| DDX25 | TNP1 | P09430 | 434 |
| DDX25 | MAEL | Q96JY0 | 433 |
IntAct
14 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| DDX19B | MIF4GD | psi-mi:“MI:0914”(association) | 0.870 |
| DDX19A | MIF4GD | psi-mi:“MI:0914”(association) | 0.860 |
| TFIP11 | DDX25 | psi-mi:“MI:0915”(physical association) | 0.560 |
| NFKBID | DDX25 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SH3BGRL | MYO1C | psi-mi:“MI:0914”(association) | 0.350 |
| NRAS | IGKV2D-24 | psi-mi:“MI:0914”(association) | 0.350 |
| psi-mi:“MI:0914”(association) | 0.350 | ||
| DDX25 | TFIP11 | psi-mi:“MI:0915”(physical association) | 0.000 |
| DDX25 | NFKBID | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (8): DDX25 (Affinity Capture-MS), DDX25 (Affinity Capture-MS), DDX25 (Two-hybrid), NFKBID (Two-hybrid), DDX25 (Affinity Capture-MS), DDX25 (Affinity Capture-RNA), DDX25 (Affinity Capture-MS), DDX25 (Affinity Capture-MS)
ESM2 similar proteins: A0A023PXF5, A6QSQ0, A6SBT4, A7EY76, F1RCY6, O13559, O18475, O48534, P18708, P40105, P40434, P40889, P43538, P46063, P46459, P46460, P46461, P54351, Q14527, Q1EB85, Q2TBP1, Q2U587, Q3B7N1, Q3E7Y4, Q5R410, Q5RF63, Q6AYJ1, Q6PCN7, Q7ZU90, Q86WJ1, Q8NHQ9, Q8R5F7, Q95216, Q96C10, Q99J87, Q9BYX4, Q9CXF7, Q9DGP9, Q9EPU0, Q9FF61
Diamond homologs: A1CFV3, A1CJT5, A1CYG5, A1D7N3, A2QEN5, A2QUY7, A3GFI4, A3GH91, A4HRK0, A4QVP2, A4RIF1, A5A6N4, A5DB98, A5DBI5, A5DVM3, A5DZX2, A6RC50, A6RJ45, A6SBT4, A6ZNQ1, A6ZQJ1, A7EGL7, A7EY76, O02494, O61305, O62591, P0CQ70, P0CQ71, P0CQ86, P0CQ87, P10081, P10630, P20449, P27639, P29562, P35683, P41376, P41378, P41379, P41381
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
106 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 0 |
| Uncertain significance | 70 |
| Likely benign | 2 |
| Benign | 28 |
Top pathogenic / likely-pathogenic (1)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1328946 | NM_013264.5(DDX25):c.1129C>T (p.Arg377Ter) | Pathogenic |
SpliceAI
2411 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 11:125904431:G:GT | donor_gain | 1.0000 |
| 11:125904481:G:GT | donor_gain | 1.0000 |
| 11:125904576:GCCAC:G | donor_gain | 1.0000 |
| 11:125904581:G:GG | donor_gain | 1.0000 |
| 11:125905210:A:AG | acceptor_gain | 1.0000 |
| 11:125905211:G:GG | acceptor_gain | 1.0000 |
| 11:125905542:A:AG | acceptor_gain | 1.0000 |
| 11:125905543:T:G | acceptor_gain | 1.0000 |
| 11:125905591:GAT:G | donor_gain | 1.0000 |
| 11:125906072:A:AG | acceptor_gain | 1.0000 |
| 11:125906072:AGT:A | acceptor_gain | 1.0000 |
| 11:125906072:AGTG:A | acceptor_gain | 1.0000 |
| 11:125906073:G:GC | acceptor_gain | 1.0000 |
| 11:125906073:GT:G | acceptor_gain | 1.0000 |
| 11:125906073:GTG:G | acceptor_gain | 1.0000 |
| 11:125906073:GTGG:G | acceptor_gain | 1.0000 |
| 11:125906210:G:GG | donor_gain | 1.0000 |
| 11:125908289:G:GG | donor_gain | 1.0000 |
| 11:125908302:G:T | donor_gain | 1.0000 |
| 11:125910479:G:GG | donor_gain | 1.0000 |
| 11:125910489:G:GG | donor_gain | 1.0000 |
| 11:125921185:TTCTA:T | acceptor_loss | 1.0000 |
| 11:125921186:TCTA:T | acceptor_loss | 1.0000 |
| 11:125921187:CTA:C | acceptor_loss | 1.0000 |
| 11:125921188:TA:T | acceptor_loss | 1.0000 |
| 11:125921189:A:AT | acceptor_loss | 1.0000 |
| 11:125921375:CTTTA:C | donor_gain | 1.0000 |
| 11:125921376:TTTA:T | donor_gain | 1.0000 |
| 11:125921376:TTTAG:T | donor_loss | 1.0000 |
| 11:125921377:TTA:T | donor_gain | 1.0000 |
AlphaMissense
3195 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 11:125917243:T:C | F344L | 1.000 |
| 11:125917245:C:A | F344L | 1.000 |
| 11:125917245:C:G | F344L | 1.000 |
| 11:125917248:C:G | C345W | 0.999 |
| 11:125918739:T:C | F384L | 0.999 |
| 11:125918740:T:C | F384S | 0.999 |
| 11:125918741:T:A | F384L | 0.999 |
| 11:125918741:T:G | F384L | 0.999 |
| 11:125918764:T:C | L392P | 0.999 |
| 11:125918767:T:A | I393K | 0.999 |
| 11:125921225:C:A | N412K | 0.999 |
| 11:125921225:C:G | N412K | 0.999 |
| 11:125921277:C:G | H430D | 0.999 |
| 11:125921280:C:A | R431S | 0.999 |
| 11:125921281:G:C | R431P | 0.999 |
| 11:125921290:G:C | R434P | 0.999 |
| 11:125906193:T:C | F99L | 0.998 |
| 11:125906195:T:A | F99L | 0.998 |
| 11:125906195:T:G | F99L | 0.998 |
| 11:125917199:T:C | L329P | 0.998 |
| 11:125917234:G:C | A341P | 0.998 |
| 11:125918640:G:C | A351P | 0.998 |
| 11:125918650:T:C | L354S | 0.998 |
| 11:125918719:G:C | R377P | 0.998 |
| 11:125918764:T:A | L392H | 0.998 |
| 11:125918767:T:G | I393R | 0.998 |
| 11:125918790:G:A | G401R | 0.998 |
| 11:125918790:G:C | G401R | 0.998 |
| 11:125921218:T:A | V410D | 0.998 |
| 11:125921287:G:A | G433E | 0.998 |
dbSNP variants (sampled 300 via entrez): RS1000030391 (11:125905970 C>T), RS1000303732 (11:125924223 T>C), RS1000478233 (11:125918533 T>C,G), RS1000594025 (11:125912401 T>A,C), RS1000655688 (11:125924613 A>G), RS1000750411 (11:125915537 A>C), RS1000774965 (11:125906742 C>G), RS1000837239 (11:125901401 C>A), RS1001008009 (11:125904347 C>G), RS1001023478 (11:125922169 A>C,T), RS1001048000 (11:125912044 G>A,C), RS1001260557 (11:125923710 A>C,G), RS1001351765 (11:125908898 G>A), RS1001645720 (11:125920748 T>C), RS1001673589 (11:125905412 T>A)
Disease associations
OMIM: gene MIM:607663 | disease phenotypes:
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| male infertility with azoospermia or oligozoospermia due to single gene mutation | Moderate | Autosomal recessive |
Mondo (2): azoospermia (MONDO:0100459), (MONDO:0018393)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
3 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST006135_8 | Cortical amyloid beta load | 2.000000e-06 |
| GCST008839_338 | Height | 1.000000e-09 |
| GCST010796_3815 | Electrocardiogram morphology (amplitude at temporal datapoints) | 2.000000e-08 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0007707 | cerebral amyloid deposition measurement |
| EFO:0004327 | electrocardiography |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D053713 | Azoospermia | C12.100.500.430.380; C12.100.750.700.380; C12.200.294.430.380 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: no
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
1 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs56819906 | DDX25 | 0.00 | 0 |
CTD chemical–gene interactions
18 total (human), top 18 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects cotreatment, decreases expression, affects expression | 7 |
| Benzo(a)pyrene | decreases expression, increases methylation | 2 |
| Phenylmercuric Acetate | affects cotreatment, decreases expression | 2 |
| Tretinoin | decreases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
| pirinixic acid | affects binding, decreases expression, increases activity | 1 |
| trichostatin A | decreases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 1 |
| dorsomorphin | decreases expression, affects cotreatment | 1 |
| Decitabine | affects expression | 1 |
| Carbamazepine | affects expression | 1 |
| Cisplatin | affects expression | 1 |
| Diethylhexyl Phthalate | decreases expression | 1 |
| Lead | decreases expression | 1 |
| Testosterone | increases expression | 1 |
| Cadmium Chloride | increases expression | 1 |
Clinical trials (associated diseases)
27 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT02307994 | PHASE4 | UNKNOWN | Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH |
| NCT02275169 | PHASE3 | UNKNOWN | FSH Treatment for Non-obstructive Azoospermic Patients |
| NCT02544191 | PHASE2 | UNKNOWN | GnRHa Combined With hCG and hMG for Treatment of Patients With Non-obstructive Azoospermia |
| NCT03762967 | PHASE2 | UNKNOWN | Autologous Adipose-Derived Adult Stromal Vascular Cell Administration for Male Patients With Infertility |
| NCT02041910 | PHASE1/PHASE2 | UNKNOWN | Testicular Injection of Autologous Stem Cells for Treatment of Patients With Azoospermia |
| NCT00282477 | Not specified | UNKNOWN | Trial to Evaluate Erectile Function, Fertility and Sperm Count in Male Cyclists Compared to Age Matched Controls |
| NCT00484081 | Not specified | COMPLETED | Microdissection Testicular Sperm Extraction (MicroTESE) and IVF-ICSI Outcome in Non-Obstructive Azoospermia (NOA) |
| NCT00548977 | Not specified | COMPLETED | Genetic Studies Spermatogenic Failure |
| NCT01375062 | Not specified | COMPLETED | Obtaining Undifferentiated Cells From Testis Biopsy |
| NCT01509482 | Not specified | COMPLETED | Insulin Resistance in Idiopathic Oligospermia and Azoospermia |
| NCT02008799 | Not specified | UNKNOWN | Intra Testicular Artery Injection of Bone Marrow Stem Cell in Management of Azoospermia |
| NCT02339272 | Not specified | COMPLETED | Study of Synapsis and Recombination in Male Meiosis and the Implications in Infertility |
| NCT02414295 | Not specified | COMPLETED | Sperm Production in Kleinfelter Syndrome Patients After Mesenchymal Stem Cell Injection |
| NCT02418832 | Not specified | RECRUITING | Testis Needle Aspiration of Sperm in Men With Azoospermia |
| NCT02617173 | Not specified | UNKNOWN | The Effect of Low Electrical Current on Testicular Spermatocyte Count |
| NCT02773498 | Not specified | TERMINATED | Comparison of Medical Results of Testicular Sperm Extraction by Conventional Surgery and Microsurgical Track |
| NCT03497728 | Not specified | TERMINATED | Detection of Microdeletions in the Azoospermia Factor (AZF) Regions in Infertile Male Patients |
| NCT04675164 | Not specified | COMPLETED | Laser Assisted Sperm Selection of Viable Immotile Testicular Sperm in Azoospermic Infertile Men |
| NCT05479474 | Not specified | RECRUITING | Platelet Rich Plasma Testis Treatment for Infertile Men |
| NCT05628987 | Not specified | RECRUITING | The Association of Gut Microbiota and Spermatogenic Dysfunction |
| NCT05866484 | Not specified | COMPLETED | Testicular Sperm Aspiration (TESA) vs. Microfluidic Sperm Separation (MSS) |
| NCT06524258 | Not specified | COMPLETED | Testicular Elastography for Microscopic Testicular Sperm Extraction |
| NCT06841328 | Not specified | RECRUITING | Fertility Enhancement Through Regenerative Treatment in Ovaries and Testes |
| NCT06941922 | Not specified | RECRUITING | Testicular Evaluation of Azoospermia Using Micro-Ultrasound |
| NCT07074015 | Not specified | RECRUITING | IntelliWell: An AI-Assisted Imaging Platform for Detection and Location of Ultra-Rare Testicular Sperm in Surgical Specimens |
| NCT07357701 | Not specified | RECRUITING | Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI) |
| NCT07542626 | Not specified | RECRUITING | Fertility Restoration With Autografting of Cryopreserved Immature Testicular Tissue |
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): azoospermia