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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NXN
nucleoredoxin
Chromosome 17 Β· 17p13.3
NCBI Gene: 64359Ensembl: ENSG00000167693.17HGNC: HGNC:18008UniProt: Q6DKJ4
44PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
Wnt signaling pathwaythioredoxin-disulfide reductase (NADPH) activitynegative regulation of Wnt signaling pathwaynegative regulation of protein ubiquitinationrobinow syndrome, autosomal recessive 2Robinow syndromecolorectal cancerautosomal recessive Robinow syndrome
✦AI Summary

NXN (nucleoredoxin) is a redox-active multifunctional enzyme that primarily functions as a negative regulator of Wnt signaling during development and cell differentiation 1. The protein operates through redox-dependent mechanisms to suppress WNT pathway activation, potentially by preventing ubiquitination of DVL3 and promoting degradation of signaling intermediates like Snail through interaction with deubiquitinating enzymes 2. NXN is expressed in developing tissues including the pituitary gland and ventral diencephalon, where it regulates pituitary stem cell differentiation and craniofacial development 1. Clinically, NXN mutations cause autosomal recessive Robinow syndrome, a genetically heterogeneous disorder characterized by skeletal dysplasia, distinctive craniofacial features, short stature, and incompletely penetrant cardiac and palate defects 31. NXN deficiency leads to reduced WNT signaling and impaired pituitary development, suggesting endocrine complications in affected patients 1. Beyond developmental disease, NXN downregulation in hepatocellular carcinoma correlates with poor prognosis and increased metastatic potential, as NXN suppresses cancer cell proliferation and epithelial-mesenchymal transition 2. Additionally, NXN expression is altered in neuroinflammatory contexts, with epigenetic changes detected in Alzheimer's disease neurogenesis models 4. The protein also participates in alcoholic liver disease pathogenesis through interactions with the FLII/actin complex 5.

Sources cited
1
NXN regulates WNT signaling during pituitary development; NXN mutations cause Robinow syndrome with pituitary dysmorphology and craniofacial defects
PMID: 40044116
2
NXN suppresses hepatocellular carcinoma metastasis by promoting Snail degradation through interaction with DUB3
PMID: 35927236
3
NXN mutations are pathogenic in Robinow syndrome, converging on WNT/PCP signaling pathway
PMID: 35047859
4
NXN shows DNA methylation changes and altered expression in Alzheimer's disease neurogenesis models
PMID: 35406633
5
NXN interacts with FLII/actin complex and is altered during alcoholic liver disease progression
PMID: 32524749
Disease Associationsβ“˜21
robinow syndrome, autosomal recessive 2Open Targets
0.61Moderate
Robinow syndromeOpen Targets
0.56Moderate
colorectal cancerOpen Targets
0.42Moderate
autosomal recessive Robinow syndromeOpen Targets
0.37Weak
polyp of colonOpen Targets
0.36Weak
benign colon neoplasmOpen Targets
0.33Weak
vertebral column disorderOpen Targets
0.31Weak
spinal cord injuryOpen Targets
0.31Weak
inflammatory bowel diseaseOpen Targets
0.29Weak
benign neoplasm of pituitary glandOpen Targets
0.28Weak
Distal shortening of limbsOpen Targets
0.27Weak
crush injuryOpen Targets
0.27Weak
colorectal adenomaOpen Targets
0.26Weak
neurodegenerative diseaseOpen Targets
0.23Weak
musculoskeletal system diseaseOpen Targets
0.23Weak
alcohol drinkingOpen Targets
0.23Weak
Abnormality of the skeletal systemOpen Targets
0.19Weak
self-injurious ideationOpen Targets
0.17Weak
glomerulonephritisOpen Targets
0.14Weak
hepatocellular carcinomaOpen Targets
0.07Suggestive
Robinow syndrome, autosomal recessive 2UniProt
Pathogenic Variants8
NM_022463.5(NXN):c.625C>T (p.Arg209Ter)Likely pathogenic
Distal shortening of limbs|Robinow syndrome, autosomal recessive 2|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 209
NM_022463.5(NXN):c.1021_1024del (p.Ser341fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 341
NM_022463.5(NXN):c.187del (p.Asp63fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 63
NM_022463.5(NXN):c.494G>A (p.Trp165Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 165
NM_022463.5(NXN):c.382C>T (p.Arg128Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 128
NM_022463.5(NXN):c.817C>T (p.Gln273Ter)Pathogenic
Robinow syndrome, autosomal recessive 2
β˜…β˜†β˜†β˜†2020β†’ Residue 273
NM_022463.5(NXN):c.-6172_361-75725delPathogenic
Robinow syndrome, autosomal recessive 2
β˜†β˜†β˜†β˜†2019
NM_022463.5(NXN):c.1231GAG[1] (p.Glu412del)Pathogenic
Robinow syndrome, autosomal recessive 2
β˜†β˜†β˜†β˜†2019β†’ Residue 412
View on ClinVar β†—
Related Genes
CRB3Protein interaction87%CNTNAP1Protein interaction85%EPB41L5Protein interaction85%TXNProtein interaction84%NLGN1Protein interaction79%DVL1Protein interaction76%
Tissue Expression6 tissues
Brain
100%
Lung
87%
Ovary
51%
Liver
37%
Heart
35%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
NXNCRB3CNTNAP1EPB41L5TXNNLGN1DVL1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6DKJ4
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.64LoF Tolerant
pLIβ“˜
0.37Tolerant
Observed/Expected LoF0.40 [0.26–0.64]
RankingsWhere NXN stands among ~20K protein-coding genes
  • #9,627of 20,598
    Most Researched44
  • #3,100of 5,498
    Most Pathogenic Variants8
  • #4,577of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedNXN
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Molecules That Have Rarely Been Studied in Lymphatic Endothelial Cells.
PMID: 39596293
Int J Mol Sci Β· 2024
1.00
2
NXN suppresses metastasis of hepatocellular carcinoma by promoting degradation of Snail through binding to DUB3.
PMID: 35927236
Cell Death Dis Β· 2022
0.90
3
NXN Gene Epigenetic Changes in an Adult Neurogenesis Model of Alzheimer's Disease.
PMID: 35406633
Cells Β· 2022
0.80
4
Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.
PMID: 35047859
HGG Adv Β· 2022
0.70
5
Nucleoredoxin regulates WNT signaling during pituitary stem cell differentiation.
PMID: 40044116
Hum Mol Genet Β· 2025
0.60