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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FNIP2
folliculin interacting protein 2
Chromosome 4 · 4q32.1
NCBI Gene: 57600Ensembl: ENSG00000052795.14HGNC: HGNC:29280UniProt: Q9P278
29PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingATPase inhibitor activityprotein-folding chaperone bindingnegative regulation of transcription by RNA polymerase IIAbnormality of the skeletal systemsmoking cessationhypotensionhealth study participation
✦AI Summary

FNIP2 (folliculin interacting protein 2) is a key regulatory component of nutrient sensing and cellular metabolism that functions primarily as a binding partner of the tumor suppressor protein FLCN 1. FNIP2 regulates mTORC1 signaling through the non-canonical pathway by forming the FLCN-FNIP2 complex, which acts as a GTPase-activating protein (GAP) for RagC/D GTPases 2. Under amino acid-deficient conditions, FNIP2 promotes nuclear translocation of transcription factors TFEB and TFE3 by inhibiting mTORC1 activity, thereby activating autophagy and lysosomal biogenesis 3. The protein also functions as an HSP90 co-chaperone, inhibiting HSP90 ATPase activity and competing with activating co-chaperones to regulate client protein folding 1. FNIP2 can form homo- or heteromeric complexes with FNIP1, suggesting cooperative or independent functions 1. Disease relevance includes its role in Birt-Hogg-Dubé syndrome, where C-terminal FLCN mutations disrupt FNIP2 binding 1. Additionally, a polymorphism (rs2291007) in FNIP2's 3'UTR affects mRNA stability through miRNA regulation and correlates with human leanness and metabolic parameters 4. FNIP2 expression is differentially regulated in renal cell carcinomas and pancreatic cancers, where it supports tumor progression through mTORC1 activation 15.

Sources cited
1
FNIP2 interacts with FLCN and AMPK, functions as HSP90 co-chaperone, and forms multimers with FNIP1
PMID: 18403135
2
FLCN-FNIP2 complex acts as GAP for RagC/D GTPases in mTORC1 regulation
PMID: 31704029
3
FNIP2 promotes TFEB/TFE3 nuclear translocation and autophagy activation under proteotoxic stress
PMID: 41450115
4
rs2291007 polymorphism in FNIP2 3'UTR affects mRNA stability and correlates with human leanness
PMID: 36316722
5
FNIP2 expression supports tumor progression in pancreatic cancer through mTORC1 activation
PMID: 37772772
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.40Weak
smoking cessationOpen Targets
0.36Weak
hypotensionOpen Targets
0.32Weak
health study participationOpen Targets
0.30Weak
intelligenceOpen Targets
0.29Weak
Alzheimer diseaseOpen Targets
0.28Weak
insomniaOpen Targets
0.28Weak
secondary malignant neoplasmOpen Targets
0.23Weak
major depressive disorderOpen Targets
0.14Weak
mathematical abilityOpen Targets
0.05Suggestive
FTH1-related iron overloadOpen Targets
0.04Suggestive
hemochromatosis type 5Open Targets
0.04Suggestive
isolated hyperferritinemiaOpen Targets
0.04Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.04Suggestive
gallbladder diseaseOpen Targets
0.03Suggestive
frozen shoulderOpen Targets
0.03Suggestive
familial isolated hyperparathyroidismOpen Targets
0.03Suggestive
hyperparathyroidismOpen Targets
0.03Suggestive
obesityOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RRAGCProtein interaction100%LAMTOR4Protein interaction100%SLC38A9Protein interaction100%RRAGDProtein interaction100%LAMTOR3Protein interaction95%RRAGBProtein interaction95%
Tissue Expression6 tissues
Heart
100%
Liver
65%
Brain
39%
Lung
39%
Bone Marrow
31%
Ovary
15%
Gene Interaction Network
Click a node to explore
FNIP2RRAGCLAMTOR4SLC38A9RRAGDLAMTOR3RRAGB
PROTEIN STRUCTURE
Preparing viewer…
PDB7LT6 · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.31 [0.23–0.42]
RankingsWhere FNIP2 stands among ~20K protein-coding genes
  • #12,147of 20,598
    Most Researched29
  • #2,216of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedFNIP2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Lysosomal Rag-Ragulator Complex Licenses RIPK1 and Caspase-8-mediated Pyroptosis by
PMID: 35058659
Science · 2021
1.00
2
Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.
PMID: 37772772
Autophagy · 2024
0.90
3
Antagonistic roles for MITF and TFE3 in melanoma plasticity.
PMID: 40138313
Cell Rep · 2025
0.80
4
Folliculin-interacting protein FNIP2 impacts on overweight and obesity through a polymorphism in a conserved 3' untranslated region.
PMID: 36316722
Genome Biol · 2022
0.70
5
Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.
PMID: 35883484
Biomolecules · 2022
0.60