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9 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NXT2
nuclear transport factor 2 like export factor 2
Chromosome X · Xq23
NCBI Gene: 55916Ensembl: ENSG00000101888.13HGNC: HGNC:18151UniProt: Q9NPJ8
26PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolnucleoplasmprotein bindingperinuclear region of cytoplasmmale infertilitygastric carcinomagastric ulcerbasal cell carcinoma
✦AI Summary

NXT2 is a nuclear export factor that regulates protein and mRNA nuclear export. It functions as a paralog of NXT1, forming heterodimeric complexes with NXF family proteins (NXF1, NXF2, NXF3) through its conserved NTF2-like domain to facilitate nucleocytoplasmic transport 1. NXT2 exhibits testis-enriched expression and plays a critical role in spermatogenesis, particularly during early germ cell development 2. Loss-of-function variants in NXT2 cause male infertility through impaired germ cell development, highlighting its essential function in human reproduction 2. However, NXT2 knockout mice remain fertile, suggesting species-specific functional requirements 3. Beyond reproductive function, NXT2 is implicated in neurodegenerative disease pathways—it shows altered DNA methylation in Alzheimer's disease models 4 and Huntington's disease patients 5, though its mechanistic role in neurodegeneration remains unclear. Clinically, NXT2 deletions contribute to X-linked intellectual disability phenotypes 6. Recent therapeutic interest has focused on exploiting NXT1-NXT2 paralog redundancy through NXF1 targeting as a selective strategy in MYCN-amplified neuroblastoma 7.

Sources cited
1
NXT2 is essential for spermatogenesis and interacts with NXF1, NXF2, NXF3, and nuclear pore complex proteins; loss-of-function variants cause male infertility
PMID: 40624043
2
NXT2 (p15-2) is a conserved NXT1 paralog that binds TAP/NXF family proteins through NTF2-like domain architecture for mRNA export
PMID: 11073998
3
NXT2 knockout mice are fertile with normal spermatogenesis, indicating species-specific functional requirements
PMID: 29563520
4
NXT2 shows hypomethylation and altered expression in Alzheimer's disease model cells with APP-sw mutation
PMID: 22001921
5
NXT2 exhibits differentially methylated CpG sites in Huntington's disease patients compared to healthy controls
PMID: 30158895
6
NXT2 deletion within Xq22.3-q23 region contributes to X-linked intellectual disability phenotype
PMID: 23520119
7
NXT1-NXT2 paralog redundancy through shared NXF1 binding partner can be exploited therapeutically in MYCN-amplified neuroblastoma
PMID: 33883167
Disease Associationsⓘ20
male infertilityOpen Targets
0.30Weak
gastric carcinomaOpen Targets
0.07Suggestive
gastric ulcerOpen Targets
0.05Suggestive
basal cell carcinomaOpen Targets
0.05Suggestive
enthesopathyOpen Targets
0.03Suggestive
infertilityOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.01Suggestive
azoospermiaOpen Targets
0.01Suggestive
bacteriemiaOpen Targets
0.01Suggestive
oligodendrogliomaOpen Targets
0.01Suggestive
astrocytomaOpen Targets
0.01Suggestive
malariaOpen Targets
0.01Suggestive
osteosarcomaOpen Targets
0.01Suggestive
SepsisOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
melanomaOpen Targets
0.00Suggestive
type 1 diabetes mellitusOpen Targets
0.00Suggestive
Obstructive azoospermiaOpen Targets
0.00Suggestive
Pathogenic Variants1
NM_001242617.2(NXT2):c.189dup (p.Asp64Ter)Likely pathogenic
Male infertility
★☆☆☆2024→ Residue 64
View on ClinVar ↗
Related Genes
NXF1Protein interaction100%NXF2BProtein interaction100%NXF2Protein interaction96%NUTF2Protein interaction95%NUP62Protein interaction87%NUP214Protein interaction83%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
18%
Liver
18%
Lung
12%
Heart
11%
Ovary
11%
Gene Interaction Network
Click a node to explore
NXT2NXF1NXF2BNXF2NUTF2NUP62NUP214
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NPJ8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.49Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.10 [0.04–0.49]
RankingsWhere NXT2 stands among ~20K protein-coding genes
  • #12,840of 20,598
    Most Researched26
  • #5,301of 5,498
    Most Pathogenic Variants1
  • #2,922of 17,882
    Most Constrained (LOEUF)0.49 · top quartile
Genes detectedNXT2
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis.
PMID: 40624043
Nat Commun · 2025
1.00
2
The evolutionarily conserved genes: Tex37, Ccdc73, Prss55 and Nxt2 are dispensable for fertility in mice.
PMID: 29563520
Sci Rep · 2018
0.89
3
Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer.
PMID: 33883167
Cancer Discov · 2021
0.78
4
Amyloid protein-mediated differential DNA methylation status regulates gene expression in Alzheimer's disease model cell line.
PMID: 22001921
Biochem Biophys Res Commun · 2011
0.67
5
DNA Methylation Profiles in Whole Blood of Huntington's Disease Patients.
PMID: 30158895
Front Neurol · 2018
0.56