MAEL

Summary

MAEL (maelstrom spermatogenic transposon silencer, HGNC:25929) is a protein-coding gene on chromosome 1q24.1, encoding Protein maelstrom homolog (Q96JY0). Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity.

Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in male meiotic nuclear division; negative regulation of macromolecule biosynthetic process; and spermatogenesis. Predicted to act upstream of or within several processes, including homologous chromosome pairing at meiosis; intrinsic apoptotic signaling pathway in response to DNA damage; and negative regulation of macromolecule biosynthetic process. Predicted to be located in piP-body. Predicted to be active in P granule and nucleus.

Source: NCBI Gene 84944 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 39 total — 2 likely-pathogenic
• MANE Select transcript: NM_032858

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25929
Approved symbol	MAEL
Name	maelstrom spermatogenic transposon silencer
Location	1q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14904, CT128, SPATA35
Ensembl gene	ENSG00000143194
Ensembl biotype	protein_coding
OMIM	611368
Entrez	84944

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000367870, ENST00000367872, ENST00000447624, ENST00000487826, ENST00000491055, ENST00000622874

RefSeq mRNA: 3 — MANE Select: NM_032858 NM_001286377, NM_001286378, NM_032858

CCDS: CCDS1257, CCDS65712, CCDS72975

Canonical transcript exons

ENST00000367872 — 12 exons

Exon	Start	End
ENSE00000958583	166989737	166989829
ENSE00001634780	166989280	166989484
ENSE00003464295	166991378	166991477
ENSE00003488703	166994028	166994069
ENSE00003496730	167005256	167005397
ENSE00003535952	167005076	167005130
ENSE00003553307	167021668	167022214
ENSE00003576377	166992686	166992841
ENSE00003580439	167016222	167016284
ENSE00003587916	167004180	167004304
ENSE00003596340	167021085	167021160
ENSE00003788091	167017827	167017959

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 98.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4551 / max 298.6183, expressed in 22 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6419	0.2010	11
6420	0.1496	19
6415	0.0379	4
6416	0.0191	4
6418	0.0123	3
201802	0.0122	3
201801	0.0101	3
6417	0.0100	3
6421	0.0030	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.95	gold quality
oocyte	CL:0000023	98.75	gold quality
right testis	UBERON:0004534	98.29	gold quality
left testis	UBERON:0004533	98.27	gold quality
sperm	CL:0000019	98.18	gold quality
adult organism	UBERON:0007023	97.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.61	gold quality
testis	UBERON:0000473	96.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.49	gold quality
right atrium auricular region	UBERON:0006631	74.84	gold quality
cardiac atrium	UBERON:0002081	74.35	gold quality
left ventricle myocardium	UBERON:0006566	73.43	gold quality
placenta	UBERON:0001987	71.39	gold quality
prefrontal cortex	UBERON:0000451	70.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.87	gold quality
heart left ventricle	UBERON:0002084	69.61	gold quality
right frontal lobe	UBERON:0002810	69.42	gold quality
cardiac ventricle	UBERON:0002082	69.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.66	gold quality
heart	UBERON:0000948	68.44	gold quality
apex of heart	UBERON:0002098	68.13	gold quality
anterior cingulate cortex	UBERON:0009835	67.75	gold quality
frontal cortex	UBERON:0001870	67.11	gold quality
neocortex	UBERON:0001950	66.61	gold quality
kidney epithelium	UBERON:0004819	65.34	gold quality
primary visual cortex	UBERON:0002436	65.01	gold quality
cerebral cortex	UBERON:0000956	64.69	gold quality
cerebellar cortex	UBERON:0002129	63.27	gold quality
cerebellar hemisphere	UBERON:0002245	63.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	938.85
E-CURD-11	yes	549.77
E-ANND-3	yes	4.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting MAEL, 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-223-3P	99.99	70.14	1140
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-943	97.81	64.42	694
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-562	97.66	65.63	698
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 16)

• These results suggest that MAEL is a novel cancer/testis-associated gene and is regulated by DNA methylation. (PMID:19693694)
• Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3beta/Snail signaling. (PMID:23929794)
• Immunofluorescence analysis showed that MAEL co-localizes with the stress granule marker PABPC1 in stress granules during oxidative stress. MAEL may be involved in miRNA-mediated gene silencing in SGs. (PMID:24189637)
• Data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1. (PMID:27181205)
• Study demonstrated that MAEL interacts with Snail and inhibit E-cadherin promoter activity. MAEL is an oncogene that plays an important role in the development and progression of colon cancer. (PMID:27537253)
• Report found that Mael is activated in proliferating cancer cells, where it serves to maintain genetic stability. Its depletion results in an increase in reactive oxygen species, followed by apoptosis or senescence. (PMID:27926513)
• Four sterility-related genes, including BOLL, DDX4, HORMAD1, and MAEL, were found to have increased methylation at CpGs of the promoter regions and decreased mRNA expressions in nonobstructive azoospermia and hypospermatogenesis (HS) testis and are believed to be associated with HS. (PMID:28342926)
• MAEL promoter hypermethylation may have a role in de-repression of LINE-1 in human hypospermatogenesis (PMID:29095993)
• This study revealed a mechanism by which MAEL could upregulate IL8 through Akt1/RelA to direct myeloid-derived suppressor cells homing into the tumor, suggesting that MAEL could be an attractive therapeutic target and a prognostic marker against esophageal squamous cell carcinoma. (PMID:30082413)
• MAEL Cancer-Testis Antigen as a Diagnostic Marker in Primary Stages of Gastric Cancer with Helicobacter pylori Infection. (PMID:30488287)
• LINC00511 was confirmed to be beneficial for osteosarcoma development via sponging miR-618 and increasing MAEL expression (PMID:31386627)
• MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma. (PMID:33902648)
• Identification of MAEL as a promoter for the drug resistance model of iPSCs derived from T-ALL. (PMID:35488386)
• Maelstrom promotes tumor metastasis through regulation of FGFR4 and epithelial-mesenchymal transition in epithelial ovarian cancer. (PMID:35513870)
• The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia. (PMID:36779514)
• MAEL in human cancers and implications in prognostication and predicting benefit from immunotherapy over VEGFR/mTOR inhibitors in clear cell renal cell carcinoma: a bioinformatic analysis. (PMID:38301040)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mael	ENSMUSG00000040629
rattus_norvegicus	Mael	ENSRNOG00000003790
drosophila_melanogaster	mael	FBGN0016034

Protein

Protein identifiers

Protein maelstrom homolog — Q96JY0 (reviewed: Q96JY0)

All UniProt accessions (4): Q96JY0, A0A140VJP0, E9JVC4, X6RGB1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage.

Subunit / interactions. Interacts with SMARCB1, SIN3B and DDX4. Interacts with piRNA-associated proteins TDRD1, PIWIL1 and PIWIL2. Interacts with TEX19.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Testis-specific. Expressed in various cancer cell lines, probably due to demethylation of its promoter.

Similarity. Belongs to the maelstrom family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96JY0-1	1	yes
Q96JY0-2	2
Q96JY0-3	3

RefSeq proteins (3): NP_001273306, NP_001273307, NP_116247* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR024970	Maelstrom	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR039259	Protein_maelstrom	Family

Pfam: PF09011, PF13017

UniProt features (13 total): helix 6, splice variant 3, chain 1, DNA-binding region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CTO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JY0-F1	73.08	0.45

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5601884	PIWI-interacting RNA (piRNA) biogenesis
R-HSA-211000	Gene Silencing by RNA
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 109 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_MALE_GAMETE_GENERATION, USF_C, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_ORGANELLE_FISSION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ORGAN_GROWTH, WTGAAAT_UNKNOWN, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_ORGAN_GROWTH

GO Biological Process (23): negative regulation of transcription by RNA polymerase II (GO:0000122), cell morphogenesis (GO:0000902), homologous chromosome pairing at meiosis (GO:0007129), male meiotic nuclear division (GO:0007140), spermatogenesis (GO:0007283), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), fertilization (GO:0009566), regulatory ncRNA-mediated gene silencing (GO:0031047), piRNA processing (GO:0034587), ectopic germ cell programmed cell death (GO:0035234), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA-templated transcription (GO:0045892), regulation of organ growth (GO:0046620), negative regulation of developmental process (GO:0051093), regulation of miRNA-mediated gene silencing (GO:0060964), transposable element silencing by piRNA-mediated DNA methylation (GO:0141196), negative regulation of reproductive process (GO:2000242), apoptotic process (GO:0006915), DNA damage response (GO:0006974), gene expression (GO:0010467), negative regulation of gene expression (GO:0010629), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

GO Molecular Function (2): sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677)

GO Cellular Component (10): chromatin (GO:0000785), male germ cell nucleus (GO:0001673), XY body (GO:0001741), nucleus (GO:0005634), cytoplasm (GO:0005737), autosome (GO:0030849), chromatoid body (GO:0033391), P granule (GO:0043186), perinuclear region of cytoplasm (GO:0048471), piP-body (GO:0071547)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gene Silencing by RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
male gamete generation	2
developmental process involved in reproduction	2
reproductive process	2
negative regulation of biological process	2
chromosome	2
cytoplasmic ribonucleoprotein granule	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
anatomical structure morphogenesis	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
meiotic cell cycle	1
meiotic nuclear division	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
sexual reproduction	1
negative regulation of gene expression	1
regulatory ncRNA processing	1
programmed cell death involved in cell development	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
organ growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
developmental process	1
regulation of developmental process	1
miRNA-mediated post-transcriptional gene silencing	1
regulation of post-transcriptional gene silencing by regulatory ncRNA	1
transposable element silencing by heterochromatin formation	1
gene silencing by piRNA-directed DNA methylation	1
regulation of reproductive process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAEL	TDRD9	Q8NDG6	851
MAEL	DDX4	Q9NQI0	834
MAEL	PIWIL2	Q8TC59	824
MAEL	PIWIL1	Q96J94	795
MAEL	PIWIL4	Q7Z3Z4	785
MAEL	TDRD1	Q9BXT4	731
MAEL	MOV10L1	Q9BXT6	677
MAEL	PLD6	Q8N2A8	646
MAEL	TDRD6	O60522	620
MAEL	TDRD5	Q8NAT2	608
MAEL	DAZL	Q92904	603
MAEL	ASZ1	Q8WWH4	603
MAEL	TDRKH	Q9Y2W6	593
MAEL	GTSF1	Q8WW33	584
MAEL	RNF17	Q9BXT8	569

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NUDC	DNAJA2	psi-mi:“MI:0914”(association)	0.710
MAEL	BRD7	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (29): PABPC1 (Affinity Capture-MS), YBX1 (Affinity Capture-MS), KHSRP (Affinity Capture-MS), SYNCRIP (Affinity Capture-MS), EIF4A1 (Affinity Capture-MS), EIF3F (Affinity Capture-MS), ELAVL1 (Affinity Capture-MS), DDX39A (Affinity Capture-MS), EIF4B (Affinity Capture-MS), HNRNPA1 (Affinity Capture-MS), HNRNPA2B1 (Affinity Capture-MS), FUBP1 (Affinity Capture-MS), DDX1 (Affinity Capture-MS), DDX3X (Affinity Capture-MS), PABPC1 (Affinity Capture-Western)

ESM2 similar proteins: A0A7H0DN38, A3EX96, A3EXD2, G5EDY0, H2QII6, K9N4V0, O10309, O13839, O15226, O62699, O96838, P0C530, P10842, P32742, P45964, P49792, Q03607, Q09293, Q17551, Q1LVQ2, Q23238, Q26240, Q2M1D1, Q32KV2, Q4R786, Q5R8C8, Q5RBY8, Q621Q3, Q66HD5, Q6ZN28, Q752B6, Q755R3, Q86BY9, Q8AXQ3, Q8BVN9, Q8BY02, Q8CDM1, Q8T8C0, Q90703, Q921I6

Diamond homologs: A4UTQ0, Q08D62, Q32KV2, Q4R786, Q8BVN9, Q96JY0, B4IB36, B4QL99

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	32
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3024483	NM_032858.3(MAEL):c.799C>T (p.Arg267Ter)	Likely pathogenic
3024484	NM_032858.3(MAEL):c.908+1G>C	Likely pathogenic

SpliceAI

1537 predictions. Top by Δscore:

Variant	Effect	Δscore
1:166989480:GGGCG:G	donor_gain	1.0000
1:166989481:GGCGG:G	donor_gain	1.0000
1:166989482:GCG:G	donor_gain	1.0000
1:166989484:GGTAA:G	donor_loss	1.0000
1:166989485:G:GG	donor_gain	1.0000
1:166989485:GTAAG:G	donor_loss	1.0000
1:166989486:T:G	donor_loss	1.0000
1:166994070:G:GG	donor_gain	1.0000
1:167005064:T:A	acceptor_gain	1.0000
1:167005074:A:AG	acceptor_gain	1.0000
1:167005075:G:GA	acceptor_gain	1.0000
1:167005241:A:AG	acceptor_gain	1.0000
1:167005242:T:G	acceptor_gain	1.0000
1:167005245:A:AG	acceptor_gain	1.0000
1:167005248:A:AG	acceptor_gain	1.0000
1:167005248:AAT:A	acceptor_gain	1.0000
1:167005249:A:G	acceptor_gain	1.0000
1:167005249:AT:A	acceptor_gain	1.0000
1:167005250:T:G	acceptor_gain	1.0000
1:167005250:T:TA	acceptor_gain	1.0000
1:167005393:ACAAG:A	donor_loss	1.0000
1:167005394:CAAG:C	donor_loss	1.0000
1:167005395:AAGGT:A	donor_loss	1.0000
1:167005396:AGGT:A	donor_loss	1.0000
1:167005397:GGTA:G	donor_loss	1.0000
1:167005399:T:A	donor_loss	1.0000
1:167016285:G:GG	donor_gain	1.0000
1:167017824:AAGGT:A	acceptor_loss	1.0000
1:167017825:AGGT:A	acceptor_loss	1.0000
1:167017826:G:GT	acceptor_loss	1.0000

AlphaMissense

2861 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:166989481:G:C	W43C	0.998
1:166989481:G:T	W43C	0.998
1:167005375:T:A	W275R	0.997
1:167005375:T:C	W275R	0.997
1:167017837:A:C	S307R	0.997
1:167017839:T:A	S307R	0.997
1:167017839:T:G	S307R	0.997
1:166989456:C:A	A35D	0.996
1:166989479:T:A	W43R	0.996
1:166989479:T:C	W43R	0.996
1:166989383:T:G	Y11D	0.994
1:166989480:G:C	W43S	0.994
1:167016223:T:C	C283R	0.994
1:166989417:T:C	L22P	0.993
1:166989455:G:C	A35P	0.993
1:166992781:T:C	C141R	0.993
1:167016256:T:C	C294R	0.993
1:166992790:T:G	Y144D	0.992
1:166989393:T:C	F14S	0.991
1:166989764:T:G	Y54D	0.991
1:166992724:A:C	S122R	0.991
1:166992726:C:A	S122R	0.991
1:166992726:C:G	S122R	0.991
1:166994051:T:C	F169L	0.991
1:166994053:T:A	F169L	0.991
1:166994053:T:G	F169L	0.991
1:166994057:T:C	C171R	0.991
1:166989765:A:C	Y54S	0.990
1:166994045:T:C	F167L	0.990
1:166994047:T:A	F167L	0.990

dbSNP variants (sampled 300 via entrez): RS1000007490 (1:167007784 T>G), RS1000178162 (1:167013304 A>G), RS1000201863 (1:167014739 C>G,T), RS1000220081 (1:167001717 G>A,C), RS1000280076 (1:167008526 T>C,G), RS1000291662 (1:166995848 T>G), RS1000307349 (1:167014619 G>T), RS1000416406 (1:167008073 T>TA), RS1000505298 (1:167013400 G>GT), RS1000648152 (1:167002675 A>G), RS1000674636 (1:166999930 G>A,T), RS1000717484 (1:167001543 C>T), RS1000741630 (1:166996895 C>T), RS1000880736 (1:166984563 A>G), RS1000925267 (1:166989899 G>A)

Disease associations

OMIM: gene MIM:611368 | disease phenotypes:

GenCC curated gene-disease

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

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002685_11	Refractive astigmatism	3.000000e-06
GCST010697_48	Cortical surface area (min-P)	3.000000e-13
GCST010698_42	Subcortical volume (min-P)	8.000000e-12
GCST010699_55	Brain morphology (min-P)	2.000000e-40
GCST010700_39	Cortical thickness (MOSTest)	4.000000e-08
GCST010701_100	Cortical surface area (MOSTest)	1.000000e-12
GCST010702_40	Subcortical volume (MOSTest)	2.000000e-10
GCST010703_26	Brain morphology (MOSTest)	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	4
sodium arsenite	affects expression, increases expression	2
terbufos	increases methylation	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	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
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Fonofos	increases methylation	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Parathion	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

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