GFI1 Gene - Growth Factor Independent 1 Transcriptional Repressor
Comprehensive gene card for GFI1, a zinc finger transcriptional repressor involved in hematopoiesis and associated with severe congenital neutropenia and acute myeloid leukemia.
Gene Information Card
| Symbol | GFI1 |
|---|---|
| Full Name | Growth Factor Independent 1 Transcriptional Repressor |
| Gene Type | Protein coding |
| Chromosomal Location | 1p22.1 |
| NCBI Gene ID | 2672 ncbi.nlm.nih.gov/gene/2672 |
| Ensembl ID | ENSG00000162676 |
| UniProt ID | Q99684 |
| OMIM ID | 600871 |
| HGNC ID | 4237 |
| Aliases | GFI-1, ZNF163, SCN2 |
Description
GFI1 (Growth Factor Independent 1) is a nuclear zinc finger protein that functions as a transcriptional repressor. It plays a critical role in hematopoiesis, particularly in the development and differentiation of myeloid and lymphoid lineages. GFI1 represses target genes by recruiting histone deacetylase complexes. Mutations in GFI1 are associated with severe congenital neutropenia type 2 (SCN2) and have been implicated in acute myeloid leukemia (AML).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe congenital neutropenia 2 (SCN2) | Loss-of-function mutations in GFI1 impair granulopoiesis, leading to a block in neutrophil differentiation. | OMIM #613107; ClinVar; multiple case reports |
| Acute myeloid leukemia (AML) | GFI1 mutations and altered expression contribute to leukemogenesis by disrupting transcriptional regulation of hematopoietic stem cell self-renewal and differentiation. | COSMIC; NCBI PubMed; OMIM |
| Non-Hodgkin lymphoma | GFI1 overexpression or aberrant activation may promote lymphomagenesis through repression of tumor suppressor genes. | NCBI PubMed; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Thymus | 6.1 | Low |
| Lymph node | 5.4 | Low |
| Whole blood | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | Myelogenous leukemia cell line |
| HL-60 (promyeloblast) | 18.7 | Acute promyelocytic leukemia |
| THP-1 (monocytic) | 9.8 | Acute monocytic leukemia |
| Jurkat (T-cell) | 4.5 | T-cell leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.880C>T (p.Arg294*) | Nonsense | Rare | Loss of function; truncation of zinc finger domain |
| c.649G>A (p.Gly217Ser) | Missense | Rare | Loss of function; impaired DNA binding |
| c.1132C>T (p.Arg378Trp) | Missense | Rare | Loss of function; reduced transcriptional repression |
| c.1003C>T (p.Arg335*) | Nonsense | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most GFI1 mutations in severe congenital neutropenia are loss-of-function, leading to reduced transcriptional repression and impaired granulopoiesis.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for GFI1; overexpression in some cancers may mimic gain-of-function effects.
Dominant Negative (DN)
Some missense mutations (e.g., p.Gly217Ser) may act in a dominant-negative manner by interfering with wild-type GFI1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hematopoietic stem cell differentiation
• Transcriptional misregulation in cancer (KEGG hsa05202)
• p53 signaling pathway (indirect regulation)
Protein Summary
GFI1 is a 422-amino acid nuclear protein containing six C2H2-type zinc finger domains that mediate sequence-specific DNA binding. It functions as a transcriptional repressor by recruiting histone deacetylase complexes (e.g., HDAC1, HDAC2) to target gene promoters. GFI1 is essential for normal hematopoiesis, particularly for granulocyte differentiation and maintenance of hematopoietic stem cell quiescence. Loss of GFI1 function leads to severe congenital neutropenia, while aberrant expression is linked to leukemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GFI1 Knockout HEK293 Cell Line | EDJ-KQ3243 | Human | 2672 | Details Get a Quote |
| GFI1B Knockout HEK293 Cell Line | EDJ-KQ6199 | Human | 8328 | Details Get a Quote |
| GFI1 Knockout HCT 116 Cell Line | EDJ-KQ24765 | Human | 2672 | Details Get a Quote |
| GFI1 Knockout HeLa Cell Line | EDJ-KQ53330 | Human | 2672 | Details Get a Quote |
| GFI1B Knockout HeLa Cell Line | EDJ-KQ54856 | Human | 8328 | Details Get a Quote |
| GFI1 Knockout A-549 Cell Line | EDJ-KQ61811 | Human | 2672 | Details Get a Quote |
| GFI1B Knockout A-549 Cell Line | EDJ-KQ63343 | Human | 8328 | Details Get a Quote |
| GFI1B Knockout HCT 116 Cell Line | EDJ-KQ71812 | Human | 8328 | Details Get a Quote |
