This gene encodes a protein that binds to the tumor suppressor protein folliculin and to AMP-activated protein kinase (AMPK). The encoded protein participates in the regulation of cellular metabolism and nutrient sensing by modulating the AMPK and target of rapamycin signaling pathways. This gene has a closely related paralog that encodes a protein with similar binding activiti... See more...

Aliases for FNIP1 Gene

Aliases for FNIP1 Gene

  • Folliculin Interacting Protein 1 2 3 5
  • Folliculin-Interacting Protein 1 3 4
  • KIAA1961 2 4
  • FNIP1 5

External Ids for FNIP1 Gene

Previous GeneCards Identifiers for FNIP1 Gene

  • GC00U921652
  • GC03M008999
  • GC05M130792
  • GC05M131006
  • GC05M130977
  • GC05M126169
  • GC05M130761

Summaries for FNIP1 Gene

Entrez Gene Summary for FNIP1 Gene

  • This gene encodes a protein that binds to the tumor suppressor protein folliculin and to AMP-activated protein kinase (AMPK). The encoded protein participates in the regulation of cellular metabolism and nutrient sensing by modulating the AMPK and target of rapamycin signaling pathways. This gene has a closely related paralog that encodes a protein with similar binding activities. Both related proteins also associate with the molecular chaperone heat shock protein-90 (Hsp90) and negatively regulate its ATPase activity and facilitate its association with folliculin. [provided by RefSeq, Jul 2017]

GeneCards Summary for FNIP1 Gene

FNIP1 (Folliculin Interacting Protein 1) is a Protein Coding gene. Diseases associated with FNIP1 include Interdigitating Dendritic Cell Sarcoma and Multilocular Clear Cell Renal Cell Carcinoma. Among its related pathways are mTOR signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include guanyl-nucleotide exchange factor activity. An important paralog of this gene is FNIP2.

UniProtKB/Swiss-Prot Summary for FNIP1 Gene

  • Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases (PubMed:24081491). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Required for B-cell development (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FNIP1 Gene

Genomics for FNIP1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for FNIP1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FNIP1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FNIP1

Top Transcription factor binding sites by QIAGEN in the FNIP1 gene promoter:
  • aMEF-2
  • AML1a
  • HTF
  • ISGF-3
  • MEF-2A
  • Meis-1
  • Meis-1a
  • Meis-1b
  • RORalpha2
  • Spz1

Genomic Locations for FNIP1 Gene

Genomic Locations for FNIP1 Gene
chr5:131,641,714-131,797,063
(GRCh38/hg38)
Size:
155,350 bases
Orientation:
Minus strand
chr5:130,977,407-131,132,756
(GRCh37/hg19)
Size:
155,350 bases
Orientation:
Minus strand

Genomic View for FNIP1 Gene

Genes around FNIP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FNIP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FNIP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FNIP1 Gene

Proteins for FNIP1 Gene

  • Protein details for FNIP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TF40-FNIP1_HUMAN
    Recommended name:
    Folliculin-interacting protein 1
    Protein Accession:
    Q8TF40
    Secondary Accessions:
    • D6RJH5
    • Q86T47
    • Q9BUT0

    Protein attributes for FNIP1 Gene

    Size:
    1166 amino acids
    Molecular mass:
    130555 Da
    Quaternary structure:
    • Homodimer and homomultimer (PubMed:18403135, PubMed:27353360). Heterodimer and heteromultimer with FNIP2 (PubMed:18403135, PubMed:27353360). Interacts with FLCN (via C-terminus) (PubMed:17028174, PubMed:27353360). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (By similarity). Interacts with HSPCA and with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (AMPK) (PubMed:17028174). Phosphorylated FLCN and AMPK are preferentially bound (PubMed:17028174). Interacts with HSP70, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4 (PubMed:27353360). Interacts with HSP90AA1; the interaction inhibits HSP90AA1 ATPase activity (PubMed:27353360, PubMed:30699359).

    Alternative splice isoforms for FNIP1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FNIP1 Gene

Post-translational modifications for FNIP1 Gene

  • Sequential phosphorylation by CK2 promotes its gradual interaction with HSP90AA1/Hsp90 (PubMed:30699359). Priming phosphorylation at Ser-938 is followed by relay phosphorylation at Ser-939, Ser-941, Ser-946 and Ser-948, promoting its gradual interaction with HSP90AA1/Hsp90 (PubMed:30699359). This leads to incremental inhibition of HSP90AA1/Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients (PubMed:30699359). Dephosphorylated by protein phosphatase 5 (PP5), promoting glycosylation by OGT (PubMed:30699359). Phosphorylated by AMPK (PubMed:17028174).
  • GlcNAcylation at Ser-938 by OGT following dephosphorylation by protein phosphatase 5 (PP5) promotes ubiquitination and degradation by the proteasome.
  • Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties at Lys-1119 following glycosylation by OGT, leading to its degradation by the proteasome.
  • Ubiquitination at Lys161
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for FNIP1 Gene

Domains & Families for FNIP1 Gene

Gene Families for FNIP1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for FNIP1 Gene

Suggested Antigen Peptide Sequences for FNIP1 Gene

GenScript: Design optimal peptide antigens:
  • Folliculin-interacting protein 1 (FNIP1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TF40

UniProtKB/Swiss-Prot:

FNIP1_HUMAN :
  • Belongs to the FNIP family.
Family:
  • Belongs to the FNIP family.
genes like me logo Genes that share domains with FNIP1: view

Function for FNIP1 Gene

Molecular function for FNIP1 Gene

UniProtKB/Swiss-Prot Function:
Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases (PubMed:24081491). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Required for B-cell development (By similarity).

Phenotypes From GWAS Catalog for FNIP1 Gene

Gene Ontology (GO) - Molecular Function for FNIP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IDA 22977732
GO:0005515 protein binding IPI 17028174
GO:0019899 enzyme binding IPI 30699359
GO:0042030 ATPase inhibitor activity IDA 27353360
GO:0051087 chaperone binding IDA 27353360
genes like me logo Genes that share ontologies with FNIP1: view
genes like me logo Genes that share phenotypes with FNIP1: view

Animal Models for FNIP1 Gene

MGI Knock Outs for FNIP1:

Animal Model Products

CRISPR Products

miRNA for FNIP1 Gene

miRTarBase miRNAs that target FNIP1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FNIP1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FNIP1 Gene

Localization for FNIP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FNIP1 Gene

Lysosome membrane. Cytoplasm, cytosol. Note=Localizes to lysosome membrane in amino acid-depleted conditions and relocalizes to the cytosol upon refeeding (PubMed:29848618). Colocalizes with FLCN in the cytoplasm (PubMed:18663353). {ECO:0000269 PubMed:18663353, ECO:0000269 PubMed:29848618}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FNIP1 gene
Compartment Confidence
cytosol 5
lysosome 5
nucleus 3
mitochondrion 2
endosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for FNIP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 17028174
GO:0005765 lysosomal membrane IDA 24081491
GO:0005829 cytosol IDA 24081491
genes like me logo Genes that share ontologies with FNIP1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for FNIP1 Gene

Pathways & Interactions for FNIP1 Gene

PathCards logo

SuperPathways for FNIP1 Gene

SuperPathway Contained pathways
1 mTOR signaling pathway (KEGG)
genes like me logo Genes that share pathways with FNIP1: view

Pathways by source for FNIP1 Gene

1 KEGG pathway for FNIP1 Gene

Gene Ontology (GO) - Biological Process for FNIP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 21209915
GO:0001932 regulation of protein phosphorylation IDA 18663353
GO:0001934 positive regulation of protein phosphorylation IMP 17028174
GO:0002327 immature B cell differentiation ISS --
GO:0002904 positive regulation of B cell apoptotic process ISS --
genes like me logo Genes that share ontologies with FNIP1: view

No data available for SIGNOR curated interactions for FNIP1 Gene

Drugs & Compounds for FNIP1 Gene

No Compound Related Data Available

Transcripts for FNIP1 Gene

mRNA/cDNA for FNIP1 Gene

4 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FNIP1

Alternative Splicing Database (ASD) splice patterns (SP) for FNIP1 Gene

No ASD Table

Relevant External Links for FNIP1 Gene

GeneLoc Exon Structure for
FNIP1

Expression for FNIP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FNIP1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for FNIP1 Gene

This gene is overexpressed in Testis (38.8) and Spleen (20.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FNIP1 Gene



Protein tissue co-expression partners for FNIP1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FNIP1

SOURCE GeneReport for Unigene cluster for FNIP1 Gene:

Hs.591273

mRNA Expression by UniProt/SwissProt for FNIP1 Gene:

Q8TF40-FNIP1_HUMAN
Tissue specificity: Strong expression is found in the heart, liver placenta, muscle, nasal mucosa, salivary gland and uvula and moderate expression in kidney and lung. Higher levels detected in clear cell renal cell carcinoma (RCC) and chromophobe RCC than in normal kidney tissue.

Evidence on tissue expression from TISSUES for FNIP1 Gene

  • Liver(4.5)
  • Muscle(4.5)
  • Nervous system(4.5)
  • Lung(4.4)
  • Kidney(2.7)
  • Blood(2.4)
  • Lymph node(2.3)
  • Eye(2.3)
  • Thyroid gland(2.2)
  • Heart(2.1)
  • Spleen(2)
genes like me logo Genes that share expression patterns with FNIP1: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for FNIP1 Gene

Orthologs for FNIP1 Gene

This gene was present in the common ancestor of animals.

Orthologs for FNIP1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia FNIP1 30 31
  • 99.77 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia FNIP1 30 31
  • 93.71 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia FNIP1 30 31
  • 93.14 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Fnip1 30 17 31
  • 90.64 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Fnip1 30
  • 90.64 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia FNIP1 31
  • 84 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia FNIP1 31
  • 82 (a)
OneToOne
Chicken
(Gallus gallus)
Aves FNIP1 30 31
  • 75.82 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia FNIP1 31
  • 76 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia fnip1 30
  • 72.61 (n)
Zebrafish
(Danio rerio)
Actinopterygii FNIP1 31
  • 66 (a)
OneToOne
fnip1 30
  • 63.3 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG3764 31
  • 7 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea T04C4.1 31
  • 13 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 44 (a)
OneToMany
Species where no ortholog for FNIP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for FNIP1 Gene

ENSEMBL:
Gene Tree for FNIP1 (if available)
TreeFam:
Gene Tree for FNIP1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FNIP1: view image

Paralogs for FNIP1 Gene

Paralogs for FNIP1 Gene

(2) SIMAP similar genes for FNIP1 Gene using alignment to 2 proteins:

  • FNIP1_HUMAN
  • J3KNG8_HUMAN
genes like me logo Genes that share paralogs with FNIP1: view

Variants for FNIP1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FNIP1 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
rs1554092867 Uncertain Significance: Wolff-Parkinson-White pattern 131,671,687(-) CTCTT/C FRAMESHIFT_VARIANT
rs1554096246 Uncertain Significance: Wolff-Parkinson-White pattern 131,719,316(-) C/T SPLICE_DONOR_VARIANT
rs12109782 - p.Val738Leu
rs13177318 - p.Ser354Leu
rs26008 - p.Gln648Arg

Additional dbSNP identifiers (rs#s) for FNIP1 Gene

Structural Variations from Database of Genomic Variants (DGV) for FNIP1 Gene

Variant ID Type Subtype PubMed ID
esv1136463 CNV deletion 17803354
esv1591239 CNV deletion 17803354
esv2730780 CNV deletion 23290073
esv2730781 CNV deletion 23290073
esv2730782 CNV deletion 23290073
esv3570416 CNV loss 25503493
esv3575881 CNV gain 25503493
esv990609 CNV deletion 20482838
nsv1032888 CNV loss 25217958
nsv1074871 CNV deletion 25765185
nsv1117579 CNV deletion 24896259
nsv968984 CNV duplication 23825009

Variation tolerance for FNIP1 Gene

Residual Variation Intolerance Score: 11.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.14; 61.48% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FNIP1 Gene

Human Gene Mutation Database (HGMD)
FNIP1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FNIP1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FNIP1 Gene

Disorders for FNIP1 Gene

MalaCards: The human disease database

(15) MalaCards diseases for FNIP1 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search FNIP1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for FNIP1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with FNIP1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FNIP1 Gene

Publications for FNIP1 Gene

  1. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. (PMID: 17028174) Baba M … Zbar B (Proceedings of the National Academy of Sciences of the United States of America 2006) 2 3 4
  2. Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins. (PMID: 11853319) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2001) 2 3 4
  3. Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90. (PMID: 30699359) Sager RA … Mollapour M (Cell reports 2019) 3 4
  4. GATOR1-dependent recruitment of FLCN-FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids. (PMID: 29848618) Meng J … Ferguson SM (The Journal of cell biology 2018) 3 4
  5. The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. (PMID: 27353360) Woodford MR … Mollapour M (Nature communications 2016) 3 4

Products for FNIP1 Gene

Sources for FNIP1 Gene