Human Gene GFI1 (ENST00000294702.6) from GENCODE V44
  Description: Homo sapiens growth factor independent 1 transcriptional repressor (GFI1), transcript variant 1, mRNA. (from RefSeq NM_005263)
RefSeq Summary (NM_005263): This gene encodes a nuclear zinc finger protein that functions as a transcriptional repressor. This protein plays a role in diverse developmental contexts, including hematopoiesis and oncogenesis. It functions as part of a complex along with other cofactors to control histone modifications that lead to silencing of the target gene promoters. Mutations in this gene cause autosomal dominant severe congenital neutropenia, and also dominant nonimmune chronic idiopathic neutropenia of adults, which are heterogeneous hematopoietic disorders that cause predispositions to leukemias and infections. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000294702.6
Gencode Gene: ENSG00000162676.13
Transcript (Including UTRs)
   Position: hg38 chr1:92,473,043-92,486,925 Size: 13,883 Total Exon Count: 7 Strand: -
Coding Region
   Position: hg38 chr1:92,476,029-92,483,487 Size: 7,459 Coding Exon Count: 6 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:92,473,043-92,486,925)mRNA (may differ from genome)Protein (422 aa)
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HGNCHPRDLynxMalacardsMGIneXtProt
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-  Comments and Description Text from UniProtKB
  ID: GFI1_HUMAN
DESCRIPTION: RecName: Full=Zinc finger protein Gfi-1; AltName: Full=Growth factor independent protein 1; AltName: Full=Zinc finger protein 163;
FUNCTION: Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2- GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development. Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin- mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA. Cooperates with CBFA2T2 to regulate ITGB1- dependent neurite growth. Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters. Required for the maintenance of inner ear hair cells.
SUBUNIT: Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2 (By similarity). Also interacts with HDAC1. Interacts (via the zinc- finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3- mediated transcriptional activity. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation of H3 (H3K9Me2) and repress expression of target genes. Interacts directly with EHMT2. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly with AJUBA (via ITS LIM domains); the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes and, occurs independently of the SNAG domain. Interacts with SPI1; the interaction inhibits SPI1 transcriptional activity and represses SPI1-regulated macrophage-specific genes required for proper granulocyte development. Interacts with RUNX1T1; the interaction represses HDAC-mediated transcriptional activity. Interacts with RELA; the interaction occurs on liposaccharide (LPS) stimulation and controls RELA DNA binding activity and regulates endotoxin-mediated TOLL-like receptor inflammatory response. Interacts (via the C-terminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 and CDKN1B promoters and repression of transcription.
INTERACTION: Q91XC0:Ajuba (xeno); NbExp=4; IntAct=EBI-949368, EBI-1565930; Q13111:CHAF1A; NbExp=4; IntAct=EBI-949368, EBI-1020839; Q96KQ7:EHMT2; NbExp=2; IntAct=EBI-949368, EBI-744366; Q13547:HDAC1; NbExp=4; IntAct=EBI-949368, EBI-301834; Q9NQX1:PRDM5; NbExp=2; IntAct=EBI-949368, EBI-4292031; Q04206:RELA; NbExp=2; IntAct=EBI-949368, EBI-73886; P17433:Spi1 (xeno); NbExp=2; IntAct=EBI-949368, EBI-607588;
SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with PIAS3 and RUNX1T1 in nuclear dots.
INDUCTION: Down-regulated by TGFB1.
DOMAIN: Zinc fingers 3, 4 and 5 are required for DNA-binding and for interaction with SPI1.
DOMAIN: The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors (By similarity).
PTM: Ubiquitinated. Ubiquitination and degradation by the proteasome is inhibited by the ubiquitin ligase, ARIH2.
DISEASE: Defects in GFI1 are a cause of neutropenia severe congenital autosomal dominant type 2 (SCN2) [MIM:613107]. SCN2 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
DISEASE: Defects in GFI1 are a cause of dominant nonimmune chronic idiopathic neutropenia of adults (NI-CINA) [MIM:607847]. NI-CINA is a relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients.
SIMILARITY: Contains 6 C2H2-type zinc fingers.
WEB RESOURCE: Name=GFI1base; Note=GFI1 mutation db; URL="http://bioinf.uta.fi/GFI1base/";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: GFI1
Diseases sorted by gene-association score: neutropenia, severe congenital 2, autosomal dominant* (1379), neutropenia, nonimmune chronic idiopathic, of adults* (1250), idiopathic neutropenia* (539), severe congenital neutropenia autosomal dominant* (202), neutropenia (32), severe congenital neutropenia (19), reticular dysgenesis (16), specific granule deficiency (8), neuroblastoma (1), leukemia, acute myeloid (0)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.64 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 34.12 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -143.50299-0.480 Picture PostScript Text
3' UTR -841.702986-0.282 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd
IPR001878 - Znf_CCHC

Pfam Domains:
PF00096 - Zinc finger, C2H2 type

ModBase Predicted Comparative 3D Structure on Q99684
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0005515 protein binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0010956 negative regulation of calcidiol 1-monooxygenase activity
GO:0010957 negative regulation of vitamin D biosynthetic process
GO:0010977 negative regulation of neuron projection development
GO:0016032 viral process
GO:0030097 hemopoiesis
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0034121 regulation of toll-like receptor signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:0051569 regulation of histone H3-K4 methylation
GO:0070105 positive regulation of interleukin-6-mediated signaling pathway
GO:0071222 cellular response to lipopolysaccharide

Cellular Component:
GO:0005634 nucleus
GO:0016363 nuclear matrix
GO:0016604 nuclear body
GO:0017053 transcriptional repressor complex


-  Descriptions from all associated GenBank mRNAs
  AK123009 - Homo sapiens cDNA FLJ16812 fis, clone THYMU3025865, highly similar to Zinc finger protein GFI-1.
U67369 - Homo sapiens growth factor independence-1 (Gfi-1) mRNA, complete cds.
BC032751 - Homo sapiens growth factor independent 1 transcription repressor, mRNA (cDNA clone MGC:45244 IMAGE:5585794), complete cds.
JD563819 - Sequence 544843 from Patent EP1572962.
JD174395 - Sequence 155419 from Patent EP1572962.
JD512377 - Sequence 493401 from Patent EP1572962.
JD499349 - Sequence 480373 from Patent EP1572962.
JD549540 - Sequence 530564 from Patent EP1572962.
JD451700 - Sequence 432724 from Patent EP1572962.
JD321669 - Sequence 302693 from Patent EP1572962.
JD059519 - Sequence 40543 from Patent EP1572962.
JD410909 - Sequence 391933 from Patent EP1572962.
JD042468 - Sequence 23492 from Patent EP1572962.
AB209606 - Homo sapiens mRNA for Zinc finger protein Gfi-1 variant protein.
JD201608 - Sequence 182632 from Patent EP1572962.
JD318849 - Sequence 299873 from Patent EP1572962.
JD269411 - Sequence 250435 from Patent EP1572962.
BC074866 - Homo sapiens growth factor independent 1 transcription repressor, mRNA (cDNA clone MGC:104022 IMAGE:30915466), complete cds.
BC074867 - Homo sapiens growth factor independent 1 transcription repressor, mRNA (cDNA clone MGC:103849 IMAGE:30915231), complete cds.
JD412228 - Sequence 393252 from Patent EP1572962.
JD333925 - Sequence 314949 from Patent EP1572962.
AK313876 - Homo sapiens cDNA, FLJ94509.
DQ891273 - Synthetic construct clone IMAGE:100003903; FLH170635.01X; RZPDo839H0898D growth factor independent 1 (GFI1) gene, encodes complete protein.
DQ894461 - Synthetic construct Homo sapiens clone IMAGE:100008921; FLH170631.01L; RZPDo839H0897D growth factor independent 1 (GFI1) gene, encodes complete protein.
AB463058 - Synthetic construct DNA, clone: pF1KB4800, Homo sapiens GFI1 gene for growth factor independent 1 transcription repressor, without stop codon, in Flexi system.
DL492421 - Novel nucleic acids.
DL490900 - Novel nucleic acids.
DL491817 - Novel nucleic acids.
DL490391 - Novel nucleic acids.
DL492457 - Novel nucleic acids.
JD278624 - Sequence 259648 from Patent EP1572962.
JD174368 - Sequence 155392 from Patent EP1572962.
JD407728 - Sequence 388752 from Patent EP1572962.
JD310233 - Sequence 291257 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000294702.1, ENST00000294702.2, ENST00000294702.3, ENST00000294702.4, ENST00000294702.5, GFI1_HUMAN, NM_005263, Q8N564, Q99684, uc001dow.1, uc001dow.2, uc001dow.3, uc001dow.4, uc001dow.5, uc001dow.6, ZNF163
UCSC ID: ENST00000294702.6
RefSeq Accession: NM_005263
Protein: Q99684 (aka GFI1_HUMAN)
CCDS: CCDS30773.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.