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    FDFT1 farnesyl-diphosphate farnesyltransferase 1 [ Homo sapiens (human) ]

    Gene ID: 2222, updated on 10-Dec-2024

    Summary

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    Official Symbol
    FDFT1provided by HGNC
    Official Full Name
    farnesyl-diphosphate farnesyltransferase 1provided by HGNC
    Primary source
    HGNC:HGNC:3629
    See related
    Ensembl:ENSG00000079459 MIM:184420; AllianceGenome:HGNC:3629
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SS; SQS; DGPT; ERG9; SQSD
    Summary
    This gene encodes a membrane-associated enzyme located at a branch point in the mevalonate pathway. The encoded protein is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 32.6), colon (RPKM 26.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FDFT1 in Genome Data Viewer
    Location:
    8p23.1
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (11795582..11839298)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (7901010..7944714, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (11653091..11696807)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901888 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:11627369-11627869 Neighboring gene nei like DNA glycosylase 2 Neighboring gene uncharacterized LOC105379243 Neighboring gene Sharpr-MPRA regulatory region 11637 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11657524-11658167 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11658297-11659039 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11659040-11659781 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27032 Neighboring gene SUB1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18941 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27033 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18942 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18943 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27034 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27035 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11705639-11706333 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:11706334-11707027 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:11707258-11707440 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11710619-11711226 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:11714811-11715344 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27036 Neighboring gene cathepsin B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27037 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27038 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18944 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18945 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:11734657-11735174 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:11735175-11735690 Neighboring gene CRISPRi-validated cis-regulatory element chr8.429 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:11748634-11748817 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:11759741-11760242 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:11768552-11769052 Neighboring gene olfactory receptor family 7 subfamily E member 158 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Molecular cloning and functional analysis of the promoter of the human squalene synthase gene. Guan G, et al. J Biol Chem, 1995 Sep 15. PMID 7665618
    2. Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression. Weng ML, et al. Nat Commun, 2020 Apr 20. PMID 32313017, Free PMC Article
    3. Squalene Synthase Deficiency. Adam MP, et al. , 1993. PMID 32027475
    4. Characterization of farnesyl diphosphate farnesyl transferase 1 (FDFT1) expression in cancer. Tüzmen Ş, et al. Per Med, 2019 Jan. PMID 30468409
    5. Discovering Peptide Inhibitors of Human Squalene Synthase Through Screening the Phage-Displayed Cyclic Peptide c7c Library. Shiuan D, et al. Appl Biochem Biotechnol, 2016 Jun. PMID 26922723

    See all (122) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Spectroscopic diagnosis and metabolite characterization of cisplatin resistance regulated by FDFT1 in bladder cancer tissue.
      Title: Spectroscopic diagnosis and metabolite characterization of cisplatin resistance regulated by FDFT1 in bladder cancer tissue.
    2. Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase.
      Title: Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase.
    3. Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression.
      Title: Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression.
    4. Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1.
      Title: Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1.
    5. FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism.
      Title: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression.
    6. We have demonstrated the differential relative expression levels of FDFT1 mRNA and protein in various types of cancer based on TMAs and IHC for protein expression, and qPCR analysis for the illustration of mRNA expression.
      Title: Characterization of farnesyl diphosphate farnesyl transferase 1 (FDFT1) expression in cancer.
    7. The results indicate that the ennea-peptide CLSPHSMFC, tetra-peptides SMFC, CKTE, and WHQW can effectively inhibit Squalene Synthase activities (IC50 values equal to 64, 76, 87, and 90 muM, respectively)
      Title: Discovering Peptide Inhibitors of Human Squalene Synthase Through Screening the Phage-Displayed Cyclic Peptide c7c Library.
    8. The minor allele in FDFT1 was associated with advanced fibrosis in the non-steatotic but not in the steatotic subgroup in patients with chronic hepatitis C.
      Title: Role of FDFT1 polymorphism for fibrosis progression in patients with chronic hepatitis C.
    9. Up-regulation of SQS promotes metastasis of lung cancer by enhancing tumor necrosis factor-alpha receptor 1 and nuclear factor-kappaB activation and matrix metallopeptidase 1 expression.
      Title: Squalene synthase induces tumor necrosis factor receptor 1 enrichment in lipid rafts to promote lung cancer metastasis.
    10. Several critical residues that are involved in binding of NADPH have been identified in the active site of squalene synthase.
      Title: Structural insights into the catalytic mechanism of human squalene synthase.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Squalene synthase deficiency
    MedGen: C4748427 OMIM: 618156 GeneReviews: Squalene Synthase Deficiency
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus.
    EBI GWAS Catalog
    Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
    EBI GWAS Catalog
    Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables squalene synthase [NAD(P)H] activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in cholesterol biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in farnesyl diphosphate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in steroid biosynthetic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in endoplasmic reticulum membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    squalene synthase
    Names
    FPP:FPP farnesyltransferase
    presqualene-di-diphosphate synthase
    squalene synthetase
    NP_001274671.1
    NP_001274672.1
    NP_001274673.1
    NP_001274674.1
    NP_001274676.1
    NP_001274677.1
    NP_001274678.1
    NP_001274679.1
    NP_001274680.1
    NP_001274685.1
    NP_004453.3

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001287742.2 → NP_001274671.1  squalene synthase isoform 1

      See identical proteins and their annotated locations for NP_001274671.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript (1) and encodes the longest isoform (1). Variants 1-3 encode the same isoform.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS5985.1
      UniProtKB/Swiss-Prot
      B3KQ95, B4DJE5, B4DT56, B7Z1J3, P37268, Q96GT0
      UniProtKB/TrEMBL
      E9PNM1, Q6IAX1
      Conserved Domains (1) summary
      TIGR01559
      Location:38 → 370
      squal_synth; farnesyl-diphosphate farnesyltransferase

    2. NM_001287743.2 → NP_001274672.1  squalene synthase isoform 1

      See identical proteins and their annotated locations for NP_001274672.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks a 5' non-coding exon compared to variant 1. Variants 1-3 encode the same isoform (1).
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS5985.1
      UniProtKB/Swiss-Prot
      B3KQ95, B4DJE5, B4DT56, B7Z1J3, P37268, Q96GT0
      UniProtKB/TrEMBL
      E9PNM1, Q6IAX1
      Related
      ENSP00000481481.1, ENST00000615631.5
      Conserved Domains (1) summary
      TIGR01559
      Location:38 → 370
      squal_synth; farnesyl-diphosphate farnesyltransferase

    3. NM_001287744.2 → NP_001274673.1  squalene synthase isoform 2

      See identical proteins and their annotated locations for NP_001274673.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) lacks 2 exons in the 5' region and initiates translation from an in-frame downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1. Variants 4-8 encode the same isoform.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS75696.1
      UniProtKB/TrEMBL
      B7Z9R8
      Conserved Domains (1) summary
      cl00210
      Location:1 → 306
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    4. NM_001287745.2 → NP_001274674.1  squalene synthase isoform 2

      See identical proteins and their annotated locations for NP_001274674.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) differs at the 5' end and initiates translation from an in-frame downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1. Variants 4-8 encode the same isoform.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS75696.1
      UniProtKB/TrEMBL
      B7Z9R8
      Conserved Domains (1) summary
      cl00210
      Location:1 → 306
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    5. NM_001287747.2 → NP_001274676.1  squalene synthase isoform 2

      See identical proteins and their annotated locations for NP_001274676.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) differs at the 5' end and initiates translation from an in-frame downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1. Variants 4-8 encode the same isoform.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS75696.1
      UniProtKB/TrEMBL
      B7Z9R8
      Related
      ENSP00000431749.1, ENST00000528812.5
      Conserved Domains (1) summary
      cl00210
      Location:1 → 306
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    6. NM_001287748.2 → NP_001274677.1  squalene synthase isoform 2

      See identical proteins and their annotated locations for NP_001274677.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (7) differs at the 5' end and initiates translation from an in-frame downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1. Variants 4-8 encode the same isoform.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS75696.1
      UniProtKB/TrEMBL
      B7Z9R8
      Related
      ENSP00000484122.1, ENST00000622850.3
      Conserved Domains (1) summary
      cl00210
      Location:1 → 306
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    7. NM_001287749.2 → NP_001274678.1  squalene synthase isoform 2

      See identical proteins and their annotated locations for NP_001274678.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (8) differs at the 5' end and initiates translation from an in-frame downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1. Variants 4-8 encode the same isoform.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS75696.1
      UniProtKB/TrEMBL
      B7Z9R8
      Related
      ENSP00000432331.1, ENST00000530664.5
      Conserved Domains (1) summary
      cl00210
      Location:1 → 306
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    8. NM_001287750.2 → NP_001274679.1  squalene synthase isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (9) lacks several exons from the 5' end, contains an alternate 5' terminal exon, and initiates translation from an alternate in-frame start codon compared to variant 1. The resulting longer isoform (3) has a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS87579.1
      UniProtKB/TrEMBL
      A0A1W2PQ47, B4DND3
      Related
      ENSP00000491537.1, ENST00000525954.5
      Conserved Domains (1) summary
      TIGR01559
      Location:97 → 429
      squal_synth; farnesyl-diphosphate farnesyltransferase

    9. NM_001287751.2 → NP_001274680.1  squalene synthase isoform 4

      See identical proteins and their annotated locations for NP_001274680.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (10) lacks several exons from the 5' end, contains an alternate 5' terminal exon, and initiates translation from an in-frame downstream start codon compared to variant 1. The resulting isoform (4) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS75697.1
      UniProtKB/TrEMBL
      B7Z9R8
      Related
      ENSP00000431649.1, ENST00000528643.5
      Conserved Domains (1) summary
      cl00210
      Location:1 → 285
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    10. NM_001287756.2 → NP_001274685.1  squalene synthase isoform 5

      See identical proteins and their annotated locations for NP_001274685.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (11) differs at the 5' end, lacks several internal exons, uses alternate donor and acceptor splice sites, and initiates translation from an alternate start codon compared to variant 1. The resulting shorter isoform (5) has a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AC069185
      UniProtKB/TrEMBL
      B4DWP0
      Related
      ENST00000446331.6
      Conserved Domains (1) summary
      cl00210
      Location:22 → 203
      Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

    11. NM_004462.5 → NP_004453.3  squalene synthase isoform 1

      See identical proteins and their annotated locations for NP_004453.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1-3 encode the same isoform (1).
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS5985.1
      UniProtKB/Swiss-Prot
      B3KQ95, B4DJE5, B4DT56, B7Z1J3, P37268, Q96GT0
      UniProtKB/TrEMBL
      E9PNM1, Q6IAX1
      Related
      ENSP00000220584.4, ENST00000220584.9
      Conserved Domains (1) summary
      TIGR01559
      Location:38 → 370
      squal_synth; farnesyl-diphosphate farnesyltransferase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      11795582..11839298
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654717.1 Reference GRCh38.p14 PATCHES

      Range
      1508774..1552517 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      7901010..7944714 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P37268.1 GenPept UniProtKB/Swiss-Prot:P37268

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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