GFI1B

growth factor independent 1B transcriptional repressor, the group of Zinc fingers C2H2-type|MicroRNA protein coding host genes|SNAG transcriptional repressors

Basic information

Region (hg38): 9:132944000-132991687

Links

ENSG00000165702 ∙ NCBI:8328 ∙ OMIM:604383 ∙ HGNC:4238 ∙ Uniprot:Q5VTD9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• platelet-type bleeding disorder 17 (Strong), mode of inheritance: AD
• platelet storage pool deficiency (Supportive), mode of inheritance: AD
• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• platelet-type bleeding disorder 17 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 17	AD	Hematologic	Individuals have increased bleeding tendency (of variable severity), and awareness may allow preventive measures and early management of bleeding complications	Hematologic	5681484; 1065298; 23927492; 24325358

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFI1B gene.

• Inborn_genetic_diseases (35 variants)
• not_provided (27 variants)
• Platelet-type_bleeding_disorder_17 (23 variants)
• not_specified (19 variants)
• GFI1B-related_disorder (15 variants)
• Factor_V_and_factor_VIII,_combined_deficiency_of,_type_1 (3 variants)
• Thrombocytopenia (2 variants)
• Abnormal_bleeding (1 variants)
• Storage_pool_disease_of_platelets (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFI1B gene is commonly pathogenic or not. These statistics are base on transcript: NM_001377304.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	1	9
missense	4	4	56	6	6	76
nonsense	2		1			3
start loss						0
frameshift	2		1			3
splice donor/acceptor (+/-2bp)	1					1
Total	9	4	58	14	7

Highest pathogenic variant AF is 0.000228699

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFI1B	protein_coding	protein_coding	ENST00000339463	6	46152

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000523	0.974	125705	0	33	125738	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.496	192	212	0.904	0.0000145	2171
Missense in Polyphen		65	89.955	0.72259		846
Synonymous	-0.686	97	88.8	1.09	0.00000616	640
Loss of Function	1.97	8	16.7	0.479	9.89e-7	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000211
Ashkenazi Jewish	0.00	0.00
East Asian	0.00117	0.00114
Finnish	0.00	0.00
European (Non-Finnish)	0.0000354	0.0000352
Middle Eastern	0.00117	0.00114
South Asian	0.0000999	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. Transcriptional repressor or activator depending on both promoter and cell type context; represses promoter activity of SOCS1 and SOCS3 and thus, may regulate cytokine signaling pathways. Cooperates with GATA1 to repress target gene transcription, such as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic cell lines markedly increase apoptosis rate. Inhibits down- regulation of MYC and MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells. Represses expression of GATA3 in T-cell lymphomas and inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 and GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells. Suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction. Binds to gamma- satellite DNA and to its own promoter, auto-repressing its own expression. Alters histone methylation by recruiting histone methyltransferase to target genes promoters. Plays a role in heterochromatin formation. {ECO:0000269|PubMed:12351384, ECO:0000269|PubMed:16177182, ECO:0000269|PubMed:16688220, ECO:0000269|PubMed:16782810, ECO:0000269|PubMed:17156408, ECO:0000269|PubMed:17272506, ECO:0000269|PubMed:17420275}.
• Disease: DISEASE: Bleeding disorder, platelet-type 17 (BDPLT17) [MIM:187900]: An autosomal dominant disorder characterized by increased bleeding tendency due to platelet dysfunction, and associated with macrothrombocytopenia and red cell anisopoikilocytosis. Platelets appear abnormal on light microscopy, while electron microscopy shows a heterogeneous decrease of alpha granules within platelets. Bone marrow biopsy shows increased numbers of abnormal megakaryocytes, suggesting a defect in megakaryopoiesis and platelet production. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other exhibit only abnormal bleeding with surgery. {ECO:0000269|PubMed:23927492, ECO:0000269|PubMed:24325358}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.626
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.38

Haploinsufficiency Scores

• pHI: 0.456
• hipred: Y
• hipred_score: 0.539
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gfi1b
• Phenotype: embryo phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: gfi1b
• Affected structure: erythroid lineage cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin organization;transcription by RNA polymerase II;multicellular organism development;cell population proliferation
• Cellular component: nucleus;transcription factor complex;nuclear matrix
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;DNA binding;protein binding;metal ion binding