GFI1

growth factor independent 1 transcriptional repressor, the group of SNAG transcriptional repressors|Zinc fingers C2H2-type

Basic information

Region (hg38): 1:92473042-92486925

Previous symbols: [ "ZNF163" ]

Links

ENSG00000162676 ∙ NCBI:2672 ∙ OMIM:600871 ∙ HGNC:4237 ∙ Uniprot:Q99684 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant severe congenital neutropenia (Supportive), mode of inheritance: AD
• neutropenia, severe congenital, 2, autosomal dominant (Limited), mode of inheritance: AD
• severe congenital neutropenia (Moderate), mode of inheritance: AD
• neutropenia, severe congenital, 2, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital, 2 autosomal dominant; Neutropenia, nonimmune chronic idiopathic, of adults	AD	Allergy/Immunology/Infectious; Oncologic	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition may predispose to leukemia, and thus surveillance for hematologic anomalies may allow early diagnosis and treatment	Allergy/Immunology/Infectious; Oncologic	1810106; 12778173; 12963840; 20560965

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFI1 gene.

• Neutropenia, severe congenital, 2, autosomal dominant (230 variants)
• not specified (38 variants)
• not provided (35 variants)
• Inborn genetic diseases (11 variants)
• Severe congenital neutropenia (9 variants)
• Nonimmune chronic idiopathic neutropenia of adults;Neutropenia, severe congenital, 2, autosomal dominant (5 variants)
• Neutropenia, severe congenital, 2, autosomal dominant;Nonimmune chronic idiopathic neutropenia of adults (4 variants)
• Nonimmune chronic idiopathic neutropenia of adults (2 variants)
• GFI1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFI1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	51	6	61
missense	1		114	5	2	122
nonsense						0
start loss						0
frameshift			2			2
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			4	16	6	26
non coding				15	6	21
Total	1	0	123	71	14

Variants in GFI1

This is a list of pathogenic ClinVar variants found in the GFI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-92475800-A-G			Benign (Jun 19, 2021)
1-92476041-A-G		Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (Jul 17, 2023)
1-92476047-C-T		Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (May 19, 2023)
1-92476048-G-A		Neutropenia, severe congenital, 2, autosomal dominant • not specified	Conflicting classifications of pathogenicity (Jan 29, 2024)
1-92476053-C-A		Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (Oct 13, 2023)
1-92476053-C-G		Neutropenia, severe congenital, 2, autosomal dominant	Benign (Jan 18, 2024)
1-92476054-C-T		Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Oct 13, 2023)
1-92476055-G-A			Uncertain significance (Jan 06, 2022)
1-92476056-G-A		not specified • Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (Nov 25, 2023)
1-92476059-C-T		Neutropenia, severe congenital, 2, autosomal dominant	Benign (Dec 20, 2023)
1-92476063-C-G			Uncertain significance (Apr 01, 2021)
1-92476089-C-T		Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (Dec 04, 2023)
1-92476090-T-C		Nonimmune chronic idiopathic neutropenia of adults • Neutropenia, severe congenital, 2, autosomal dominant	Conflicting classifications of pathogenicity (May 30, 2023)
1-92476100-G-A		Neutropenia, severe congenital, 2, autosomal dominant • not specified	Benign (Jan 29, 2024)
1-92476104-G-A		Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (Nov 19, 2020)
1-92476108-C-A		Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Apr 11, 2022)
1-92476109-C-T		Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Nov 18, 2022)
1-92476110-G-A		Neutropenia, severe congenital, 2, autosomal dominant • GFI1-related disorder	Benign/Likely benign (Oct 24, 2023)
1-92476126-G-A		Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Dec 08, 2020)
1-92476136-G-A		Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Mar 03, 2023)
1-92476153-T-C		Neutropenia, severe congenital, 2, autosomal dominant	Pathogenic (Mar 01, 2018)
1-92476166-T-C		Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Aug 01, 2022)
1-92476172-C-T		GFI1-related disorder • Neutropenia, severe congenital, 2, autosomal dominant	Uncertain significance (Jun 02, 2023)
1-92476178-C-T		Neutropenia, severe congenital, 2, autosomal dominant • not specified	Uncertain significance (Dec 08, 2022)
1-92476179-G-A		Neutropenia, severe congenital, 2, autosomal dominant	Likely benign (Dec 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFI1	protein_coding	protein_coding	ENST00000370332	6	12115

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.255	0.744	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	177	247	0.716	0.0000132	2670
Missense in Polyphen		37	90.726	0.40782		992
Synonymous	2.53	78	112	0.696	0.00000612	859
Loss of Function	2.83	4	16.3	0.245	7.04e-7	195

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000367	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.000107	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:11060035, ECO:0000269|PubMed:12778173, ECO:0000269|PubMed:16287849, ECO:0000269|PubMed:17197705, ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:18805794, ECO:0000269|PubMed:19026687, ECO:0000269|PubMed:19164764, ECO:0000269|PubMed:20190815, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:8754800}.
• Disease: DISEASE: Neutropenia, severe congenital 2, autosomal dominant (SCN2) [MIM:613107]: A disorder of hematopoiesis characterized by 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. {ECO:0000269|PubMed:12778173}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dominant nonimmune chronic idiopathic neutropenia of adults (NI-CINA) [MIM:607847]: Relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients. {ECO:0000269|PubMed:12778173}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Development and heterogeneity of the ILC family;Validated targets of C-MYC transcriptional repression (Consensus)

Recessive Scores

• pRec: 0.288

Intolerance Scores

• loftool: 0.557
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.27

Haploinsufficiency Scores

• pHI: 0.363
• hipred: Y
• hipred_score: 0.828
• ghis: 0.410

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gfi1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: gfi1aa
• Affected structure: myeloid lineage restricted progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: regulation of transcription involved in G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;negative regulation of calcidiol 1-monooxygenase activity;negative regulation of vitamin D biosynthetic process;negative regulation of neuron projection development;viral process;hemopoiesis;negative regulation of NF-kappaB transcription factor activity;regulation of toll-like receptor signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of histone H3-K4 methylation;positive regulation of interleukin-6-mediated signaling pathway;cellular response to lipopolysaccharide
• Cellular component: nucleus;nucleoplasm;nuclear matrix;nuclear body;transcriptional repressor complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;transcription regulatory region DNA binding;metal ion binding