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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NANOS2
nanos C2HC-type zinc finger 2
Chromosome 19 · 19q13.32
NCBI Gene: 339345Ensembl: ENSG00000188425.4HGNC: HGNC:23292UniProt: P60321
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleuscytoplasmprotein bindingenzyme activator activityneurodegenerative diseasedementiaintracranial hemorrhageazoospermia
✦AI Summary

NANOS2 is a testis-specific germ cell regulator that plays a pivotal role in male sexual differentiation 1. As an RNA-binding protein, NANOS2 promotes male germ cell fate by suppressing female developmental pathways 2. Mechanistically, NANOS2 represses meiosis through interaction with the CCR4-NOT deadenylation complex, which it recruits to target mRNAs via its N-terminal domain 3. Notably, NANOS2 functions cooperatively with DND1 protein to select target mRNAs, acting as a second-layer recognition factor beyond simple CNOT complex recruitment 4. This repression prevents STRA8 expression, blocking premeiotic DNA replication and maintaining spermatogonial stem cell populations 5. NANOS2 expression is regulated by retinoic acid signaling, which inhibits NANOS2 to permit spermatogonial differentiation and meiotic entry 5. Clinically, NANOS2 mutations have been identified in infertile males with spermatogenic abnormalities, though causality remains unclear 1. Significantly, absence of NANOS2 expression in embryonic germ cells is associated with testicular teratoma development, implicating NANOS2 as a critical safeguard against germ cell transformation 6.

Sources cited
1
NANOS2 is testis-specific and present in human prenatal germ cells and spermatogenesis; mutations identified in infertile males
PMID: 19168545
2
NANOS2 promotes male germ cell fate by suppressing female developmental pathways
PMID: 18430166
3
NANOS2 N-terminal 10 amino acids are required for interaction with CCR4-NOT deadenylation complex CNOT1 component, essential for male germ cell development
PMID: 22448252
4
NANOS2 cooperates with DND1 to select target mRNAs and recruit CNOT complex for mRNA repression
PMID: 35705038
5
Retinoic acid inhibits NANOS2 to promote spermatogonial differentiation and meiotic entry through STRA8 upregulation
PMID: 35673893
6
NANOS2-deficient embryonic germ cells fail to differentiate and develop pluripotent transcriptional profiles; embryonal carcinoma cells arise exclusively from NANOS2-negative germ cells
PMID: 33912935
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.38Weak
dementiaOpen Targets
0.20Weak
intracranial hemorrhageOpen Targets
0.15Weak
azoospermiaOpen Targets
0.11Weak
partial chromosome Y deletionOpen Targets
0.10Suggestive
spermatogenic failure 50Open Targets
0.10Suggestive
spermatogenic failure 57Open Targets
0.10Suggestive
spermatogenic failure 71Open Targets
0.10Suggestive
spermatogenic failure 25Open Targets
0.09Suggestive
spermatogenic failure 61Open Targets
0.09Suggestive
spermatogenic failure 62Open Targets
0.09Suggestive
spermatogenic failure 88Open Targets
0.09Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.09Suggestive
spermatogenic failure 59Open Targets
0.09Suggestive
spermatogenic failure 60Open Targets
0.09Suggestive
spermatogenic failure 73Open Targets
0.09Suggestive
spermatogenic failure 74Open Targets
0.09Suggestive
spermatogenic failure 48Open Targets
0.09Suggestive
spermatogenic failure 12Open Targets
0.09Suggestive
spermatogenic failure 22Open Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CYP26B1Protein interaction96%BTG3Protein interaction83%GFRA1Protein interaction78%CNOT2Protein interaction77%CNOT3Protein interaction77%CNOT8Protein interaction77%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
50%
Liver
0%
Ovary
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
NANOS2CYP26B1BTG3GFRA1CNOT2CNOT3CNOT8
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P60321
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.14LoF Tolerant
pLIⓘ
0.25Tolerant
Observed/Expected LoF0.44 [0.20–1.14]
RankingsWhere NANOS2 stands among ~20K protein-coding genes
  • #14,750of 20,598
    Most Researched18
  • #11,867of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedNANOS2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The highly conserved NANOS2 protein: testis-specific expression and significance for the human male reproduction.
PMID: 19168545
Mol Hum Reprod · 2009
1.00
2
Nanos3 not nanos1 and nanos2 is a germ cell marker gene in large yellow croaker during embryogenesis.
PMID: 29331522
Comp Biochem Physiol B Biochem Mol Biol · 2018
0.90
3
A cooperative mechanism of target RNA selection via germ-cell-specific RNA-binding proteins NANOS2 and DND1.
PMID: 35705038
Cell Rep · 2022
0.80
4
Molecular Cloning and Sexually Dimorphic Expression Analysis of nanos2 in the Sea Urchin, Mesocentrotus nudus.
PMID: 31159444
Int J Mol Sci · 2019
0.70
5
Sexual development of mouse germ cells: Nanos2 promotes the male germ cell fate by suppressing the female pathway.
PMID: 18430166
Dev Growth Differ · 2008
0.60