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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NVL
nuclear VCP like
Chromosome 1 · 1q42.11
NCBI Gene: 4931Ensembl: ENSG00000143748.19HGNC: HGNC:8070UniProt: B4DF43
96PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of telomere maintenancenuclear exosome (RNase complex)nucleolusRNA bindingneurodegenerative diseaseParkinson diseaselysosomal storage diseasemultiple sclerosis
✦AI Summary

NVL (nuclear VCP-like) is a multifunctional AAA-ATPase that plays critical roles in telomerase assembly and ribosome biogenesis. The protein participates in telomerase holoenzyme assembly through direct interaction with TERT, which is essential for telomerase activity 1. NVL is involved in both early and late stages of pre-rRNA processing pathways and spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus 1. The protein catalyzes the ATP-dependent release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles during ribosome maturation. NVL's subcellular localization can be modulated by bacterial pathogens, as demonstrated by Brucella effectors that sequester SENP3 and promote cytoplasmic accumulation of NVL along with ribosomal protein L5 2. Disease relevance includes psychiatric disorders, as genetic variants in NVL confer overlapping risk for both major depressive disorder and schizophrenia in Han Chinese populations 1. Additionally, NVL has been identified as an autoantigen in systemic sclerosis patients, suggesting potential autoimmune implications 3. The protein's dual roles in telomerase function and ribosome biogenesis highlight its importance in cellular homeostasis and disease pathogenesis.

Sources cited
1
NVL encodes NVL2 protein that interacts with TERT for telomerase assembly and confers genetic risk for major depressive disorder and schizophrenia
PMID: 25891250
2
NVL subcellular localization is modulated by Brucella effectors through SENP3 sequestration, promoting cytoplasmic accumulation
PMID: 36609656
3
NVL identified as autoantigen in systemic sclerosis patients without known autoantibody specificity
PMID: 36634459
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
Alzheimer diseaseOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
multiple sclerosisOpen Targets
0.37Weak
Parkinson diseaseOpen Targets
0.37Weak
hypertrophic cardiomyopathyOpen Targets
0.27Weak
glioblastoma multiformeOpen Targets
0.26Weak
systemic sclerodermaOpen Targets
0.08Suggestive
diabetes mellitusOpen Targets
0.02Suggestive
Phenotypic abnormalityOpen Targets
0.02Suggestive
idiopathic interstitial pneumoniaOpen Targets
0.02Suggestive
gastritisOpen Targets
0.02Suggestive
alcohol drinkingOpen Targets
0.02Suggestive
posterior cortical atrophyOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
prostate adenocarcinomaOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
calcinosisOpen Targets
0.01Suggestive
interstitial lung diseaseOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SNRPBProtein interaction100%SNRPEProtein interaction100%MTREXProtein interaction100%NOP2Protein interaction99%NIFKProtein interaction99%BMS1Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
92%
Brain
74%
Lung
69%
Heart
58%
Liver
56%
Gene Interaction Network
Click a node to explore
NVLSNRPBSNRPEMTREXNOP2NIFKBMS1
PROTEIN STRUCTURE
Preparing viewer…
PDB2X8A · 2.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.89LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.70 [0.56–0.89]
RankingsWhere NVL stands among ~20K protein-coding genes
  • #4,996of 20,598
    Most Researched96 · top quartile
  • #8,000of 17,882
    Most Constrained (LOEUF)0.89
Genes detectedNVL
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations.
PMID: 39269178
Cancer Discov · 2024
1.00
2
NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations.
PMID: 36511802
Cancer Discov · 2023
0.90
3
Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression.
PMID: 38954874
Eur Neuropsychopharmacol · 2024
0.80
4
The NVL gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.
PMID: 25891250
Prog Neuropsychopharmacol Biol Psychiatry · 2015
0.70
5
Identification of new telomere- and telomerase-associated autoantigens in systemic sclerosis.
PMID: 36634459
J Autoimmun · 2023
0.60