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
Phenotypes
GenCC
Source:
- 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:
| 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
- Platelet-type bleeding disorder 17 (3 variants)
- Storage pool disease of platelets (1 variants)
- Inborn genetic diseases (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.
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 | 7 | |||||
| missense | 31 | 45 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 3 | 1 | 4 | |||
| non coding | 23 | 23 | ||||
| Total | 5 | 0 | 32 | 12 | 29 |
Variants in GFI1B
This is a list of pathogenic ClinVar variants found in the GFI1B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| 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:
- 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
- essential_gene_gene_trap
- 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