This gene encodes a protein that binds to the tumor suppressor folliculin and to AMP-activated protein kinase (AMPK), and may play a role cellular metabolism and nutrient sensing by regulating the AMPK-mechanistic target of rapamycin signaling pathway. The encoded protein may also be involved in regulating the O6-methylguanine-induced apoptosis signaling pathway. This gene has ... See more...

Aliases for FNIP2 Gene

Aliases for FNIP2 Gene

  • Folliculin Interacting Protein 2 2 3 5
  • O6-Methylguanine-Induced Apoptosis 1 Protein 3 4
  • Folliculin-Interacting Protein 2 3 4
  • FNIP1-Like Protein 3 4
  • FNIPL 3 4
  • MAPO1 3 4
  • O6-Methylguanine-Induced Apoptosis 1 2
  • KIAA1450 4

External Ids for FNIP2 Gene

Previous GeneCards Identifiers for FNIP2 Gene

  • GC04P159911
  • GC04P159690
  • GC04P155440

Summaries for FNIP2 Gene

Entrez Gene Summary for FNIP2 Gene

  • This gene encodes a protein that binds to the tumor suppressor folliculin and to AMP-activated protein kinase (AMPK), and may play a role cellular metabolism and nutrient sensing by regulating the AMPK-mechanistic target of rapamycin signaling pathway. The encoded protein may also be involved in regulating the O6-methylguanine-induced apoptosis signaling pathway. 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 FNIP2 Gene

FNIP2 (Folliculin Interacting Protein 2) is a Protein Coding gene. Diseases associated with FNIP2 include Familial Renal Oncocytoma and Birt-Hogg-Dube Syndrome. Among its related pathways are PI3K / Akt Signaling and mTOR signaling pathway (KEGG). An important paralog of this gene is FNIP1.

UniProtKB/Swiss-Prot Summary for FNIP2 Gene

  • Acts as a co-chaperone of HSP90AA1. Inhibits the ATPase activity of HSP90AA1 leading to reduction in its chaperone activity. Facilitates the binding of client protein FLCN to HSP90AA1 (PubMed:27353360). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By similarity). May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways (PubMed:18403135). May regulate phosphorylation of RPS6KB1 (PubMed:18663353).

Additional gene information for FNIP2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FNIP2 Gene

Genomics for FNIP2 Gene

GeneHancer (GH) Regulatory Elements for FNIP2 Gene

Promoters and enhancers for FNIP2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J158767 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 506.4 +1.2 1199 5.2 EP300 NRF1 POLR2G USF1 PHF8 POLR2A ZBTB26 TARDBP SAP30 ZBTB25 FNIP2 lnc-PPID-1 PPID RNU6-128P ETFDH RAPGEF2 RF00026-834
GH04J158804 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 539.2 +40.9 40898 11 EP300 FOXK2 ZBTB40 ZNF217 ZSCAN5C SIN3A USF1 NCOR1 JUND FOS FNIP2 piR-48772-019 PPID ETFDH RAPGEF2 C4orf45 piR-42700-104
GH04J158823 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 41.3 +56.9 56875 5.7 ZNF217 ZSCAN5C NCOR1 REST TCF7 TRIM28 MEF2C MYC TEAD1 CTBP1 FNIP2 PPID RNU6-128P ETFDH C4orf45 RAPGEF2 piR-48772-019 piR-42700-104
GH04J158819 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 37.2 +52.0 51986 3.1 SP1 EP300 MEF2C TEAD1 ZSCAN9 BCL11A FOXA2 KAT7 SAP130 MEF2B FNIP2 PPID RNU6-128P ETFDH C4orf45 RAPGEF2 piR-48772-019 piR-42700-104
GH04J158774 Promoter/Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 30.3 +6.4 6445 1.9 FOS POLR2A RFX1 NR2F2 JUND FOSL2 PRDM6 PRDM10 ZNF18 ZNF644 FNIP2 PPID RAPGEF2 RF00026-834 RNU6-128P
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FNIP2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FNIP2

Top Transcription factor binding sites by QIAGEN in the FNIP2 gene promoter:
  • HFH-1
  • HNF-3beta
  • LCR-F1
  • NF-E2
  • NF-E2 p45
  • PPAR-gamma1
  • PPAR-gamma2
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c

Genomic Locations for FNIP2 Gene

Genomic Locations for FNIP2 Gene
chr4:158,769,026-158,908,050
(GRCh38/hg38)
Size:
139,025 bases
Orientation:
Plus strand
chr4:159,690,182-159,829,201
(GRCh37/hg19)
Size:
139,020 bases
Orientation:
Plus strand

Genomic View for FNIP2 Gene

Genes around FNIP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FNIP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FNIP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FNIP2 Gene

Proteins for FNIP2 Gene

  • Protein details for FNIP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P278-FNIP2_HUMAN
    Recommended name:
    Folliculin-interacting protein 2
    Protein Accession:
    Q9P278
    Secondary Accessions:
    • Q05DC3
    • Q96I31
    • Q9H994

    Protein attributes for FNIP2 Gene

    Size:
    1114 amino acids
    Molecular mass:
    122115 Da
    Quaternary structure:
    • Homodimer and homomultimer. Heterodimer and heteromultimer with FNIP1 (PubMed:27353360, PubMed:18403135). Interacts (via C-terminus) with FLCN (via C-terminus) (PubMed:18403135, PubMed:18663353, PubMed:27353360). Phosphorylated FLCN is preferentially bound (PubMed:18663353). Interacts with PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (PubMed:18403135, PubMed:18663353). Interacts with HSP70, HSP90AA1, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4 (PubMed:27353360).
    Miscellaneous:
    • Elevated expression levels in histologic variants of renal tumors.
    SequenceCaution:
    • Sequence=AAH07861.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH16638.1; Type=Miscellaneous discrepancy; Note=Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAA95974.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14338.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for FNIP2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FNIP2 Gene

Post-translational modifications for FNIP2 Gene

No data available for DME Specific Peptides for FNIP2 Gene

Domains & Families for FNIP2 Gene

Gene Families for FNIP2 Gene

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

Protein Domains for FNIP2 Gene

Suggested Antigen Peptide Sequences for FNIP2 Gene

GenScript: Design optimal peptide antigens:
  • O6-methylguanine-induced apoptosis 1 protein (FNIP2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P278

UniProtKB/Swiss-Prot:

FNIP2_HUMAN :
  • Belongs to the FNIP family.
Family:
  • Belongs to the FNIP family.
genes like me logo Genes that share domains with FNIP2: view

Function for FNIP2 Gene

Molecular function for FNIP2 Gene

UniProtKB/Swiss-Prot Function:
Acts as a co-chaperone of HSP90AA1. Inhibits the ATPase activity of HSP90AA1 leading to reduction in its chaperone activity. Facilitates the binding of client protein FLCN to HSP90AA1 (PubMed:27353360). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (By similarity). May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways (PubMed:18403135). May regulate phosphorylation of RPS6KB1 (PubMed:18663353).

Phenotypes From GWAS Catalog for FNIP2 Gene

Gene Ontology (GO) - Molecular Function for FNIP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 18403135
GO:0042030 ATPase inhibitor activity IDA 27353360
GO:0051087 chaperone binding IDA 27353360
genes like me logo Genes that share ontologies with FNIP2: view
genes like me logo Genes that share phenotypes with FNIP2: view

Animal Models for FNIP2 Gene

MGI Knock Outs for FNIP2:
  • Fnip2 Fnip2<tm1a(KOMP)Wtsi>
  • Fnip2 Fnip2<tm1.2Lss>

Clone Products

  • Addgene plasmids for FNIP2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FNIP2 Gene

Localization for FNIP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FNIP2 Gene

Cytoplasm. Note=Colocalizes with FLCN in the cytoplasm.

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 FNIP2 gene
Compartment Confidence
cytosol 5
cytoskeleton 4
nucleus 3
plasma membrane 2
mitochondrion 2
lysosome 2
extracellular 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centriolar satellite (3)
  • Cytosol (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FNIP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 18403135
GO:0005829 cytosol IDA --
GO:0034451 centriolar satellite IDA --
genes like me logo Genes that share ontologies with FNIP2: view

Pathways & Interactions for FNIP2 Gene

PathCards logo

SuperPathways for FNIP2 Gene

genes like me logo Genes that share pathways with FNIP2: view

Pathways by source for FNIP2 Gene

1 KEGG pathway for FNIP2 Gene
1 Cell Signaling Technology pathway for FNIP2 Gene

Gene Ontology (GO) - Biological Process for FNIP2 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:0006468 protein phosphorylation IDA 18663353
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage IEA,ISS --
genes like me logo Genes that share ontologies with FNIP2: view

No data available for SIGNOR curated interactions for FNIP2 Gene

Drugs & Compounds for FNIP2 Gene

No Compound Related Data Available

Transcripts for FNIP2 Gene

mRNA/cDNA for FNIP2 Gene

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

Clone Products

  • Addgene plasmids for FNIP2

Alternative Splicing Database (ASD) splice patterns (SP) for FNIP2 Gene

No ASD Table

Relevant External Links for FNIP2 Gene

GeneLoc Exon Structure for
FNIP2

Expression for FNIP2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FNIP2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for FNIP2 Gene

This gene is overexpressed in Oral epithelium (27.6) and Monocytes (13.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for FNIP2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FNIP2

SOURCE GeneReport for Unigene cluster for FNIP2 Gene:

Hs.652441

mRNA Expression by UniProt/SwissProt for FNIP2 Gene:

Q9P278-FNIP2_HUMAN
Tissue specificity: Widely expressed with highest levels in muscle, nasal mucosa, salivary gland, uvula, fat, liver, heart, placenta and pancreas. Moderately expressed in the lung, small intestine, kidney and brain. Lower levels detected in renal cell carcinoma than in normal kidney tissue (PubMed:18403135). Higher levels detected in oncocytoma tumors than in normal kidney. Higher levels detected in renal cell carcinoma tumors than in normal kidney tissue (PubMed:27353360).

Evidence on tissue expression from TISSUES for FNIP2 Gene

  • Nervous system(4.8)
  • Kidney(2.6)
genes like me logo Genes that share expression patterns with FNIP2: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for FNIP2 Gene

Orthologs for FNIP2 Gene

This gene was present in the common ancestor of animals.

Orthologs for FNIP2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FNIP2 31 30
  • 99.25 (n)
OneToOne
dog
(Canis familiaris)
Mammalia FNIP2 31 30
  • 85.75 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Fnip2 30
  • 81.32 (n)
mouse
(Mus musculus)
Mammalia Fnip2 17 31 30
  • 80.65 (n)
cow
(Bos Taurus)
Mammalia FNIP2 31 30
  • 76.51 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FNIP2 31
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FNIP2 31
  • 64 (a)
OneToOne
chicken
(Gallus gallus)
Aves FNIP2 31 30
  • 68.22 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia FNIP2 31
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia fnip2 30
  • 63.95 (n)
zebrafish
(Danio rerio)
Actinopterygii si:ch211-42i9.8 30
  • 64.15 (n)
FNIP2 31
  • 44 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG3764 31
  • 6 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea T04C4.1 31
  • 12 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 44 (a)
OneToMany
Species where no ortholog for FNIP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 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 FNIP2 Gene

ENSEMBL:
Gene Tree for FNIP2 (if available)
TreeFam:
Gene Tree for FNIP2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FNIP2: view image

Paralogs for FNIP2 Gene

Paralogs for FNIP2 Gene

(2) SIMAP similar genes for FNIP2 Gene using alignment to 3 proteins:

  • FNIP2_HUMAN
  • D6RFH5_HUMAN
  • H0Y8F3_HUMAN
genes like me logo Genes that share paralogs with FNIP2: view

Variants for FNIP2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FNIP2 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
708521 Benign: not provided 158,868,112(+) C/T SYNONYMOUS_VARIANT
715499 Likely Benign: not provided 158,868,529(+) A/G SYNONYMOUS_VARIANT
774444 Likely Benign: not provided 158,868,858(+) G/A MISSENSE_VARIANT
774858 Benign: not provided 158,868,251(+) G/C MISSENSE_VARIANT
rs2276938 - p.Thr298Ser

Additional dbSNP identifiers (rs#s) for FNIP2 Gene

Structural Variations from Database of Genomic Variants (DGV) for FNIP2 Gene

Variant ID Type Subtype PubMed ID
dgv9332n54 CNV gain 21841781
esv22076 CNV loss 19812545
esv23058 CNV loss 19812545
esv2607605 CNV deletion 19546169
esv2675186 CNV deletion 23128226
esv2728614 CNV deletion 23290073
esv2728615 CNV deletion 23290073
esv3564857 CNV deletion 23714750
esv3602840 CNV loss 21293372
nsv1126701 CNV deletion 24896259
nsv4570 CNV deletion 18451855
nsv830125 CNV gain 17160897
nsv830127 CNV loss 17160897
nsv830128 CNV gain 17160897

Variation tolerance for FNIP2 Gene

Residual Variation Intolerance Score: 16.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.37; 70.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FNIP2 Gene

Human Gene Mutation Database (HGMD)
FNIP2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FNIP2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FNIP2 Gene

Disorders for FNIP2 Gene

MalaCards: The human disease database

(10) MalaCards diseases for FNIP2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
familial renal oncocytoma
birt-hogg-dube syndrome
  • bhd
multilocular clear cell renal cell carcinoma
  • cystadenocarcinoma of kidney
familial renal papillary carcinoma
  • hereditary papillary renal carcinoma
oncocytoma
  • oxyphilic adenoma
- elite association - COSMIC cancer census association via MalaCards
Search FNIP2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for FNIP2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with FNIP2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FNIP2 Gene

Publications for FNIP2 Gene

  1. Identification and characterization of a novel folliculin-interacting protein FNIP2. (PMID: 18403135) Hasumi H … Schmidt LS (Gene 2008) 2 3 4 54
  2. The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. (PMID: 27353360) Woodford MR … Mollapour M (Nature communications 2016) 3 4 54
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  4. A novel protein, MAPO1, that functions in apoptosis triggered by O6-methylguanine mispair in DNA. (PMID: 19137017) Komori K … Hidaka M (Oncogene 2009) 3 4 54
  5. Interaction of folliculin (Birt-Hogg-Dubé gene product) with a novel Fnip1-like (FnipL/Fnip2) protein. (PMID: 18663353) Takagi Y … Hino O (Oncogene 2008) 3 4 54

Products for FNIP2 Gene

Sources for FNIP2 Gene