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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NDN
necdin, MAGE family member
Chromosome 15 · 15q11.2
NCBI Gene: 4692Ensembl: ENSG00000182636.8HGNC: HGNC:7675UniProt: Q99608
67PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnegative regulation of transcription by RNA polymerase IInucleusnucleoplasmneurodegenerative diseasetrauma complicationcataractSubdural hemorrhage
✦AI Summary

NDN (necdin, MAGE family member) is a maternally imprinted, paternally expressed tumor suppressor gene located in the Prader-Willi syndrome (PWS) chr15 region (15q11-13) 1. NDN functions as a growth suppressor that facilitates cell cycle arrest by binding to and repressing cell-cycle-promoting proteins, similar to retinoblastoma protein, and interacts additively with p53 to inhibit cell growth 2. The gene exhibits tissue-specific and imprinted epigenetic modifications, including maternal allele-specific DNA hypermethylation of the promoter CpG island and paternal allele-specific histone hyperacetylation correlating with transcriptional activity 3. NDN expression is restricted to post-mitotic neurons in brain tissue and is highest in the hypothalamus during puberty, suggesting a role in puberty timing 4. In ovarian cancers, NDN is dramatically downregulated in 73% of cases through both genetic (loss of heterozygosity in 28% of informative cases) and epigenetic mechanisms (promoter hypermethylation in 23-30% of cancers) 2. Re-expression of NDN decreases Bcl-2 levels, induces apoptosis, inhibits cell growth and migration by deactivating Src, FAK, and RhoA 2. Recent evidence suggests NDN may contribute to PWS pathogenesis when deleted alongside MAGEL2 and MKRN3 5, though individual gene contributions remain incompletely understood.

Sources cited
1
NDN is a maternally imprinted gene expressed exclusively from paternal allele in PWS chromosomal region; located in 15q11-13; completely lacks expression in PWS brain and fibroblasts
PMID: 9354807
2
NDN is tumor suppressor downregulated in 73% of ovarian cancers; loss occurs via LOH (28%) and hypermethylation (23-30%); re-expression decreases Bcl-2, induces apoptosis, inhibits migration via Src/FAK/RhoA deactivation
PMID: 26689988
3
NDN exhibits maternal allele-specific DNA hypermethylation of promoter CpG island and paternal allele-specific histone hyperacetylation correlating with transcriptional state
PMID: 15247330
4
NDN mRNA expression highest in hypothalamus at puberty; expression significantly increases then decreases from prepuberty to postpuberty in hypothalamus, pituitary, ovary and oviduct
PMID: 38252343
5
Isolated deletion of MAGEL2, NDN, and MKRN3 can produce full PWS phenotype including neonatal hypotonia, developmental delay, hyperphagia, obesity, and behavioral issues
PMID: 40231584
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.27Weak
cataractOpen Targets
0.27Weak
trauma complicationOpen Targets
0.27Weak
Subdural hemorrhageOpen Targets
0.26Weak
tympanic membrane perforationOpen Targets
0.19Weak
Prader-Willi syndromeOpen Targets
0.19Weak
JaundiceOpen Targets
0.19Weak
protozoa infectious diseaseOpen Targets
0.18Weak
contractureOpen Targets
0.17Weak
benign soft tissue neoplasmOpen Targets
0.17Weak
liver diseaseOpen Targets
0.17Weak
adverse effectOpen Targets
0.17Weak
response to stimulusOpen Targets
0.17Weak
scoliosisOpen Targets
0.17Weak
facial painOpen Targets
0.15Weak
neoplasmOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
leukemiaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TP53Protein interaction100%UBE3AProtein interaction100%NGFRProtein interaction92%EID1Protein interaction87%SNRPNProtein interaction85%ATP10AProtein interaction83%
Tissue Expression6 tissues
Ovary
100%
Heart
67%
Brain
55%
Lung
20%
Bone Marrow
9%
Liver
7%
Gene Interaction Network
Click a node to explore
NDNTP53UBE3ANGFREID1SNRPNATP10A
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q99608
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.48Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.10 [0.04–0.48]
RankingsWhere NDN stands among ~20K protein-coding genes
  • #6,999of 20,598
    Most Researched67
  • #2,778of 17,882
    Most Constrained (LOEUF)0.48 · top quartile
Genes detectedNDN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.
PMID: 38658754
Nature · 2024
1.00
2
Cloning, tissue expression and imprinting status analysis of the NDN gene in Dolang sheep.
PMID: 38252343
Mol Biol Rep · 2024
0.90
3
The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region.
PMID: 9354807
Nat Genet · 1997
0.80
4
Tissue-specific and imprinted epigenetic modifications of the human NDN gene.
PMID: 15247330
Nucleic Acids Res · 2004
0.70
5
NDN is an imprinted tumor suppressor gene that is downregulated in ovarian cancers through genetic and epigenetic mechanisms.
PMID: 26689988
Oncotarget · 2016
0.60