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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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MAEL
maelstrom spermatogenic transposon silencer
Chromosome 1 Β· 1q24.1
NCBI Gene: 84944Ensembl: ENSG00000143194.13HGNC: HGNC:25929UniProt: A0A140VJP0
34PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sequence-specific DNA bindingmale meiotic nuclear divisionspermatogenesisregulatory ncRNA-mediated gene silencingmale infertilityinsomniaCrohn's diseaseazoospermia
✦AI Summary

MAEL (maelstrom spermatogenic transposon silencer) is a germline-specific protein with dual roles in spermatogenesis and cancer biology. Primarily, MAEL functions as a critical regulator of transposon silencing during spermatogenesis through the piRNA pathway 1. It localizes to P granules and piP-bodies, where it associates with piRNA-Piwi protein complexes to repress transposable elements and maintain genomic stability 2. Beyond its canonical germline function, MAEL is expressed in mitochondria of ejaculated spermatozoa, where it regulates ATP production and sperm motility through interactions with GPX4 and UBL4B 3. Biallelic MAEL variants cause transposon de-repression and impaired spermatogenesis, establishing piRNA pathway disruption as a major cause of human male infertility 1. Clinically, MAEL functions as a cancer/testis-associated gene, with elevated expression in multiple malignancies including clear cell renal carcinoma and breast cancer 4. In breast cancer, MAEL promotes metabolic reprogramming by facilitating chaperone-mediated autophagy-dependent degradation of Krebs cycle enzymes 5. High MAEL expression in clear cell renal carcinoma predicts favorable responses to VEGFR/mTOR inhibitors but poor outcomes with immunotherapy 4. MAEL expression is regulated by DNA methylation in its promoter region 6.

Sources cited
1
MAEL localizes to mitochondria in ejaculated spermatozoa and regulates ATP production and sperm motility through GPX4 and UBL4B interactions; MAEL deficiency is associated with asthenozoospermia
PMID: 36779514
2
Biallelic MAEL variants cause impaired piRNA biogenesis, transposon de-repression, and are a major cause of human spermatogenic failure and male infertility
PMID: 39122675
3
MAEL comprises a high mobility group box and MAEL domain and is a key player in piRNA-mediated transposon silencing in the germline
PMID: 25836734
4
MAEL is a cancer/testis gene with higher expression in testicular germ cell tumors, gliomas, and renal cell carcinomas; high MAEL in ccRCC predicts sensitivity to VEGFR/mTOR inhibitors and poor response to immunotherapy
PMID: 38301040
5
MAEL promotes breast cancer progression by facilitating chaperone-mediated autophagy-dependent degradation of citrate synthase and fumarate hydratase, promoting metabolic shift to aerobic glycolysis
PMID: 36866961
6
MAEL is a cancer/testis-associated gene expressed in testis and cancer cell lines, with a CpG island in its promoter that regulates its expression via DNA methylation
PMID: 19693694
Disease Associationsβ“˜20
male infertilityOpen Targets
0.33Weak
insomniaOpen Targets
0.32Weak
Crohn's diseaseOpen Targets
0.26Weak
azoospermiaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
metabolic syndromeOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
gastric cancerOpen Targets
0.06Suggestive
spermatogenic failure 57Open Targets
0.06Suggestive
spermatogenic failure 50Open Targets
0.06Suggestive
spermatogenic failure 25Open Targets
0.06Suggestive
spermatogenic failure 63Open Targets
0.06Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.06Suggestive
spermatogenic failure 72Open Targets
0.06Suggestive
spermatogenic failure 71Open Targets
0.06Suggestive
spermatogenic failure 18Open Targets
0.06Suggestive
spermatogenic failure 27Open Targets
0.06Suggestive
spermatogenic failure 46Open Targets
0.06Suggestive
Pathogenic Variants2
NM_032858.3(MAEL):c.799C>T (p.Arg267Ter)Likely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2023β†’ Residue 267
NM_032858.3(MAEL):c.908+1G>CLikely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
ASZ1Protein interaction92%HENMT1Protein interaction89%TDRD12Protein interaction80%TDRD9Protein interaction77%PIWIL4Protein interaction72%FKBP6Protein interaction71%
Tissue Expression6 tissues
Heart
100%
Brain
39%
Liver
3%
Ovary
1%
Bone Marrow
1%
Lung
1%
Gene Interaction Network
Click a node to explore
MAELASZ1HENMT1TDRD12TDRD9PIWIL4FKBP6
PROTEIN STRUCTURE
Preparing viewer…
PDB2CTO Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.06LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.81 [0.63–1.06]
RankingsWhere MAEL stands among ~20K protein-coding genes
  • #11,184of 20,598
    Most Researched34
  • #4,492of 5,498
    Most Pathogenic Variants2
  • #10,653of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedMAEL
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia.
PMID: 36779514
Andrology Β· 2023
1.00
2
Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.
PMID: 39122675
Nat Commun Β· 2024
0.90
3
Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells.
PMID: 25679760
Cell Β· 2015
0.80
4
Ivermectin to Control Malaria - A Cluster-Randomized Trial.
PMID: 40700688
N Engl J Med Β· 2025
0.70
5
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
Aging (Albany NY) Β· 2024
0.60