GFI1B

Summary

GFI1B (growth factor independent 1B transcriptional repressor, HGNC:4238) is a protein-coding gene on chromosome 9q34.13, encoding Zinc finger protein Gfi-1b (Q5VTD9). Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages.

This gene encodes a zinc-finger containing transcriptional regulator that is primarily expressed in cells of hematopoietic lineage. The encoded protein complexes with numerous other transcriptional regulatory proteins including GATA-1, runt-related transcription factor 1 and histone deacetylases to control expression of genes involved in the development and maturation of erythrocytes and megakaryocytes. Mutations in this gene are the cause of the autosomal dominant platelet disorder, platelet-type bleeding disorder-17. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 8328 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet-type bleeding disorder 17 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 89
• Clinical variants (ClinVar): 135 total — 8 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 24
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_001377304

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4238
Approved symbol	GFI1B
Name	growth factor independent 1B transcriptional repressor
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Aliases	ZNF163B
Ensembl gene	ENSG00000165702
Ensembl biotype	protein_coding
OMIM	604383
Entrez	8328

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000339463, ENST00000372122, ENST00000372123, ENST00000443690, ENST00000524638, ENST00000631293, ENST00000636137, ENST00000636263, ENST00000866785, ENST00000866786, ENST00000866787, ENST00000954290, ENST00000954291

RefSeq mRNA: 5 — MANE Select: NM_001377304 NM_001135031, NM_001371908, NM_001377304, NM_001377305, NM_004188

CCDS: CCDS48049, CCDS6957, CCDS94523

Canonical transcript exons

ENST00000372122 — 7 exons

Exon	Start	End
ENSE00001095653	132988197	132988468
ENSE00001095655	132989742	132989907
ENSE00001095657	132989061	132989198
ENSE00001095658	132987282	132987419
ENSE00001372714	132986659	132986778
ENSE00001456952	132990872	132991687
ENSE00001772634	132978694	132978841

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 91.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 8.2025 / max 726.0908, expressed in 166 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99181	6.3319	141
99180	0.7890	80
99179	0.4308	75
99184	0.3318	56
99182	0.1901	71
99183	0.1290	58

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	91.22	gold quality
trabecular bone tissue	UBERON:0002483	90.80	gold quality
monocyte	CL:0000576	90.19	gold quality
mononuclear cell	CL:0000842	89.82	gold quality
leukocyte	CL:0000738	88.83	gold quality
male germ cell	CL:0000015	87.68	gold quality
bone marrow	UBERON:0002371	82.32	gold quality
blood	UBERON:0000178	80.89	gold quality
left testis	UBERON:0004533	78.49	gold quality
right testis	UBERON:0004534	78.27	gold quality
granulocyte	CL:0000094	78.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.98	gold quality
testis	UBERON:0000473	75.27	gold quality
bone marrow cell	CL:0002092	73.28	gold quality
mucosa of transverse colon	UBERON:0004991	68.41	gold quality
right lung	UBERON:0002167	61.85	gold quality
stromal cell of endometrium	CL:0002255	61.76	gold quality
spleen	UBERON:0002106	59.68	gold quality
amniotic fluid	UBERON:0000173	59.35	gold quality
mucosa of sigmoid colon	UBERON:0004993	59.31	gold quality
oocyte	CL:0000023	58.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.48	silver quality
vena cava	UBERON:0004087	58.10	gold quality
cardia of stomach	UBERON:0001162	57.77	gold quality
gingival epithelium	UBERON:0001949	57.67	gold quality
colonic mucosa	UBERON:0000317	57.15	gold quality
upper lobe of left lung	UBERON:0008952	57.01	gold quality
myocardium	UBERON:0002349	56.85	gold quality
duodenum	UBERON:0002114	56.56	gold quality
gingiva	UBERON:0001828	56.23	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	41.27
E-HCAD-10	yes	15.67
E-MTAB-9067	yes	12.96
E-ANND-3	yes	9.36
E-MTAB-9388	yes	7.80
E-MTAB-9801	no	3.38

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
ADAM2
BCL2L1
CD34
CDKN1A	Unknown
DTX1
ELF4
GATA3	Repression
GFI1
GFI1B	Unknown
MEF2C	Repression
MEIS1	Repression
MYC
RUNX1T1
TGFBR3	Repression

Upstream regulators (CollecTRI, top): EBF1, GATA1, GATA2, GATA3, GFI1, GFI1B, HMGB2, NFYA, NFYB, NFYC, POU2F1, RCOR2, TCF3

miRNA regulators (miRDB)

20 targeting GFI1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-2277-3P	91.94	62.27	299

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• This zinc finger protein mediates erythroid expansion and has a role in normal erythropoiesis (PMID:12351384)
• GATA-1 and NF-Y both contribute to erythroid-specific transcriptional activation of the Gfi-1B promoter. (PMID:15280509)
• Gfi-1B acts in the late stage of erythroid differentiation as a transcriptional repressor. (PMID:15507521)
• GATA-1 and Gfi-1B participates in a feedback regulatory pathway in controlling the expression of the Gfi-1B gene. (PMID:16177182)
• E2A proteins prevent lymphoma cell expansion, at least in part through regulation of Gfi1b and modulation of Gata3 expression. (PMID:17272506)
• GATA1 and GFI1B interplay to regulate bcl-X protein transcription. (PMID:17420275)
• suggest that Gfi1b may be an important factor to establish or maintain myeloid leukemia and myeloproliferative diseases (PMID:19360458)
• Data conclude that Gfi-1B behaves as a lineage-affiliated gene with an open chromatin configuration in multipotent progenitors and sustained activation as cells progress throughout erythroid differentiation. (PMID:19522008)
• GFI1B regulatory elements behave as activators and repressors, consistent with a model in which GFI1B binds to its own promoter and to the conserved non-coding elements as its levels rise. (PMID:19773260)
• HMGB2 potentiates GATA-1-dependent transcription of GFI1B by Oct-1 and thereby controls erythroid differentiation. (PMID:19965638)
• repressing TGF-beta type III receptor (TbetaRIotaII) expression, Gfi-1B favors the Smad2/TIF1-gamma interaction downstream of TGF-beta signaling, allowing immature progenitors to differentiate toward the erythroid lineage. (PMID:20124515)
• Results reveal the presence of different protein complexes, including GATA-1 and Oct-1, involved in Gfi1b regulation. (PMID:20143233)
• Gfi-1B p32, a Gfi-1B isoform, is essential for erythroid differentiation (PMID:22399799)
• Silencing of both BCR-ABL siRNA and GFI1B siRNA is associated with an additive antileukemic effect against K562 cells. (PMID:23788109)
• a mutation in GFI1B causes a platelet disorder; GFI1B has a role a critical regulator of platelet shape, number, and function (PMID:23927492)
• Our studies show that GFI1B, in addition to being causally related to the gray platelet syndrome, is key to megakaryocyte and platelet development. (PMID:24325358)
• TAL1 is involved in regulating H3K27me3 variations in collaboration with GFI1B (PMID:24395799)
• results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate ’enhancer hijacking’ as an efficient mechanism driving oncogene activation in a childhood cancer (PMID:25043047)
• Gfi1b functions as a transcriptional repressor by recruiting histone-modifying enzymes to promoters and enhancers of target genes. Mutations are associated with certain bleeding disorders. Review. (PMID:26447191)
• SPI1-GFI1B transcriptional network is an important regulatory axis in acute myeloid leukemia as well as in the development of erythroid versus myelomonocytic cell fate (PMID:26851695)
• GFI1B is an essential protein for the normal development of the megakaryocyte lineage (PMID:27122003)
• Role for Alternative GFI1B Splice Variants in Human Hematopoiesis (PMID:27486782)
• study demonstrates the significance of Gfi1b regulated Kindlin3-Talin1 expression in driving megakaryocytic differentiation and highlights the contribution of cytoskeletal agents in the developmental progression of these platelet progenitors (PMID:27768697)
• Results demonstrate that alpha-delta platelet storage pool deficiency is associated with either a heterozygous mutation in GFI1B (de novo or familial) abrogating the binding of the zinc fingers with the promoter of its target genes, or by hypomorphic biallelic mutations leading to autosomal recessive inheritance. (PMID:28041820)
• Platelet CD34 expression and alpha/delta-granule abnormalities in GFI1B- and RUNX1-related familial bleeding disorders. (PMID:28096094)
• A novel GFI1B mutation at the first zinc finger domain causes congenital macrothrombocytopenia. (PMID:28439885)
• High GFI1B expression is associated with small-cell lung cancer. (PMID:28667074)
• Disruption of GFI1B non-DNA-binding zinc-finger 1 is associated with mild to moderate thrombocytopenia without alpha-granule deficiency or bleeding symptomatology, indicating that the site of GFI1B mutation has important phenotypic implications. Platelet CD34 expression appears to be a common feature of perturbed GFI1B function. (PMID:28880435)
• Gfi1b functions as an oncosuppressor in MDS and AML development. (PMID:29326122)
• We conclude that Q89fs, C168F, H181Y, and R184P affect GFI1B function, but are not necessarily sufficient to cause bleedings on their own. (PMID:30573501)
• Findings demonstrate the central role of the GFI1B-LSD1 interaction as a determinant of BRAF-histone deacetylase complex recruitment to enable cell fate decisions driven by GFI1B. (PMID:30988160)
• Macrothrombocytopenia associated with a rare GFI1B missense variant confounding the presentation of immune thrombocytopenia. (PMID:31207059)
• Loss of myeloid-specific lamin A/C drives lung metastasis through Gfi-1 and C/EBPepsilon-mediated granulocytic differentiation. (PMID:31912614)
• Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI 1B-dependent blood and SOX17-positive endothelium. (PMID:33028609)
• Dominant negative Gfi1b mutations cause moderate thrombocytopenia and an impaired stress thrombopoiesis associated with mild erythropoietic abnormalities in mice. (PMID:33054086)
• Dysregulation of oncogenic factors by GFI1B p32: investigation of a novel GFI1B germline mutation. (PMID:33472357)
• Specific proteome changes in platelets from individuals with GATA1-, GFI1B-, and RUNX1-linked bleeding disorders. (PMID:33690840)
• The transcription factors GFI1 and GFI1B as modulators of the innate and acquired immune response. (PMID:33993920)
• Characterization of a genomic region 8 kb downstream of GFI1B associated with myeloproliferative neoplasms. (PMID:34450246)
• Fuchs Endothelial Corneal Dystrophy associated risk variant, rs3768617 in LAMC1 shows allele specific binding of GFI1B. (PMID:35031421)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gfi1b	ENSDARG00000079947
mus_musculus	Gfi1b	ENSMUSG00000026815
rattus_norvegicus	Gfi1b	ENSRNOG00000011353

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger protein Gfi-1b — Q5VTD9 (reviewed: Q5VTD9)

Alternative names: Growth factor independent protein 1B, Potential regulator of CDKN1A translocated in CML

All UniProt accessions (3): A0A024R8F3, A0A1B0GTD0, Q5VTD9

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts directly with RCOR1, KDM1A and HDAC2. Forms a complex with GATA1. Interacts with histone methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2). Interacts with RUNX1T1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in bone marrow and fetal liver, but also detectable in fetal spleen, fetal thymus, and testes. Detected in hematopoietic stem cells, erythroblasts, and megakaryocytes. Overexpressed in bone marrow of patients with erythroleukemia and megakaryocytic leukemia as well as in their corresponding leukemic cell lines, and markedly repressed in severe aplastic anemia (SAA).

Post-translational modifications. Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The zinc finger domains are essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain. The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.

Induction. By GATA1 which binds to GFI1B promoter in cooperation with the transcription factor NFYA. Target gene of transcription factor E2-alpha/TCF3 that promotes growth arrest and apoptosis in lymphomas.

Miscellaneous. Essential for erythroid differentiation. Binds to target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major isoform 1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VTD9-1	1, p37	yes
Q5VTD9-2	2, p32

RefSeq proteins (5): NP_001128503, NP_001358837, NP_001364233, NP_001364234, NP_004179 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (20 total): zinc finger region 6, sequence conflict 5, region of interest 4, chain 1, modified residue 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTD9-F1	64.09	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 8

Mutagenesis-validated functional residues (1):

Position	Phenotype
290	prevents dna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 239 (showing top): LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, FOXD3_01, CCANNAGRKGGC_UNKNOWN, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, OCT1_03, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_MITOTIC_CELL_CYCLE, GUO_HEX_TARGETS_DN

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), regulation of hemopoiesis (GO:1903706), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), plasma membrane (GO:0005886), nuclear matrix (GO:0016363)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
nuclear lumen	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
cellular component organization	1
regulation of DNA-templated transcription	1
regulation of immune system process	1
hemopoiesis	1
regulation of cell development	1
regulation of multicellular organismal development	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
DNA-binding transcription factor binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GFI1B	KDM1A	O60341	965
GFI1B	RCOR1	Q9UKL0	964
GFI1B	HDAC1	Q13547	881
GFI1B	TAL1	P17542	872
GFI1B	GATA1	P15976	868
GFI1B	LMO2	P25791	839
GFI1B	GATA2	P23769	796
GFI1B	MEGF8	Q7Z7M0	786
GFI1B	HDAC2	Q92769	764
GFI1B	LYL1	P12980	757
GFI1B	LDB1	Q86U70	720
GFI1B	LDB2	O43679	718
GFI1B	RUNX1T1	Q06455	662
GFI1B	ITGA2B	P08514	639
GFI1B	SPI1	P17947	612

IntAct

87 interactions, top by confidence:

A	B	Type	Score
GFI1B	CPAP	psi-mi:“MI:0915”(physical association)	0.510
GFI1B	JAG2	psi-mi:“MI:0915”(physical association)	0.510
GFI1B	NELL2	psi-mi:“MI:0915”(physical association)	0.510
IL17F	GFI1B	psi-mi:“MI:0915”(physical association)	0.370
TNFSF4	GFI1B	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
GFI1B	ACTN1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	AGRN	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	BECN1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	BRCA1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	BABAM2	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	DZANK1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	CENPB	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	CPAP	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	DKFZp586M1819	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	DTNA	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	EFEMP1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	EFEMP2	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	MEGF6	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	MEGF8	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	EGFL7	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	FBLN1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	BEND5	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	GRIP2	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	GRN	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	HECW1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	HGS	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	HNRNPK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (173): GFI1B (Positive Genetic), GFI1B (Negative Genetic), GFI1B (Negative Genetic), GFI1B (Negative Genetic), GFI1B (Negative Genetic), GFI1B (Positive Genetic), GFI1B (Positive Genetic), GFI1B (Negative Genetic), GFI1B (Positive Genetic), GFI1B (Positive Genetic), GINS4 (Negative Genetic), GTF2H4 (Negative Genetic), HBS1L (Negative Genetic), INTS5 (Negative Genetic), LEO1 (Negative Genetic)

ESM2 similar proteins: A0JPB4, A0PJY2, B0K011, O08876, O15090, O57415, O62651, O70237, O75626, O95863, P19544, P22561, P41183, P49952, P55878, P86413, Q02085, Q08DS3, Q0IHB8, Q0P4W9, Q0VDQ9, Q25C93, Q28G88, Q2TAR3, Q2VWH6, Q32NK7, Q3MHQ4, Q3T135, Q3UH06, Q567J8, Q5T0B9, Q5VTD9, Q5XJQ7, Q60636, Q62255, Q66JF8, Q6AY34, Q6DBW0, Q6NRM0, Q804Q5

Diamond homologs: O42409, O57415, O70237, O77459, P28166, P60319, P70338, Q07120, Q3UH06, Q5DWN0, Q5VTD9, Q6DCW1, Q92766, Q99684, A1L2U9, B1WAZ8, B1WBU4, G5EBU4, O60315, O62836, O73590, O97581, P08048, P17010, P17012, P20271, P31509, P36197, P37275, P39770, P39806, P39956, P50481, P52739, P53410, P56270, P56670, P56671, P61375, P61376

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
GFI1B	“up-regulates quantity by expression”	MEF2C	“transcriptional regulation”
HMGB2	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
GATA1	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
NFYB	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
POU2F1	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
NFYC	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	GFI1B	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Molecules associated with elastic fibres	5	31.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

135 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	72
Likely benign	13
Benign	29

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
102428	NM_001377304.1(GFI1B):c.859C>T (p.Gln287Ter)	Pathogenic
1703853	NM_001377304.1(GFI1B):c.520A>G (p.Thr174Ala)	Pathogenic
1705843	NM_001377304.1(GFI1B):c.692G>T (p.Arg231Leu)	Pathogenic
438346	NM_001377304.1(GFI1B):c.793A>T (p.Lys265Ter)	Pathogenic
520664	NM_001377304.1(GFI1B):c.784G>A (p.Asp262Asn)	Pathogenic
585291	NM_001377304.1(GFI1B):c.724del (p.His242fs)	Pathogenic
88891	NM_001377304.1(GFI1B):c.880dup (p.His294fs)	Pathogenic
988821	NM_001377304.1(GFI1B):c.814+1G>A	Pathogenic
1684412	NM_001377304.1(GFI1B):c.521C>T (p.Thr174Ile)	Likely pathogenic
1684454	NM_001377304.1(GFI1B):c.551G>C (p.Arg184Pro)	Likely pathogenic
4077191	NM_001377304.1(GFI1B):c.648+5G>A	Likely pathogenic

SpliceAI

1781 predictions. Top by Δscore:

Variant	Effect	Δscore
9:132986654:TGCA:T	acceptor_loss	1.0000
9:132986655:GCAG:G	acceptor_loss	1.0000
9:132986656:CA:C	acceptor_loss	1.0000
9:132986657:A:AC	acceptor_loss	1.0000
9:132986657:A:AG	acceptor_gain	1.0000
9:132986657:AG:A	acceptor_gain	1.0000
9:132986657:AGGT:A	acceptor_gain	1.0000
9:132986658:G:GC	acceptor_gain	1.0000
9:132986658:GG:G	acceptor_gain	1.0000
9:132986658:GGT:G	acceptor_gain	1.0000
9:132986658:GGTG:G	acceptor_gain	1.0000
9:132986658:GGTGT:G	acceptor_gain	1.0000
9:132986742:G:GT	donor_gain	1.0000
9:132986774:CCCGG:C	donor_gain	1.0000
9:132986775:CCGG:C	donor_gain	1.0000
9:132986777:GG:G	donor_gain	1.0000
9:132986778:GG:G	donor_gain	1.0000
9:132986778:GGTG:G	donor_loss	1.0000
9:132986779:G:C	donor_loss	1.0000
9:132986779:G:GG	donor_gain	1.0000
9:132986780:T:A	donor_loss	1.0000
9:132987280:A:AG	acceptor_gain	1.0000
9:132987281:G:GA	acceptor_gain	1.0000
9:132987281:GT:G	acceptor_gain	1.0000
9:132987403:G:GT	donor_gain	1.0000
9:132988195:A:AG	acceptor_gain	1.0000
9:132988195:AGAG:A	acceptor_gain	1.0000
9:132988196:G:GG	acceptor_gain	1.0000
9:132988196:GAGG:G	acceptor_gain	1.0000
9:132988453:TGTG:T	donor_gain	1.0000

AlphaMissense

2189 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:132989151:T:C	F201L	1.000
9:132989153:C:A	F201L	1.000
9:132989153:C:G	F201L	1.000
9:132989757:T:C	C222R	1.000
9:132989778:T:C	F229L	1.000
9:132989779:T:C	F229S	1.000
9:132989780:C:A	F229L	1.000
9:132989780:C:G	F229L	1.000
9:132989797:T:C	L235P	1.000
9:132989805:C:A	H238N	1.000
9:132989805:C:G	H238D	1.000
9:132989807:C:A	H238Q	1.000
9:132989807:C:G	H238Q	1.000
9:132989809:T:C	L239P	1.000
9:132989819:C:A	H242Q	1.000
9:132989819:C:G	H242Q	1.000
9:132989841:T:C	C250R	1.000
9:132989851:G:A	C253Y	1.000
9:132989862:T:C	F257L	1.000
9:132989863:T:C	F257S	1.000
9:132989864:C:A	F257L	1.000
9:132989864:C:G	F257L	1.000
9:132989891:C:A	H266Q	1.000
9:132989891:C:G	H266Q	1.000
9:132989903:C:A	H270Q	1.000
9:132989903:C:G	H270Q	1.000
9:132990889:T:C	C278R	1.000
9:132990898:T:C	C281R	1.000
9:132990899:G:A	C281Y	1.000
9:132990910:T:A	F285I	1.000

dbSNP variants (sampled 300 via entrez): RS1000316003 (9:132993491 A>G), RS1000453286 (9:132990607 C>G,T), RS1000469670 (9:132969651 C>G,T), RS1000581543 (9:132955291 AT>A,ATT), RS1000588302 (9:132990310 C>T), RS1000630077 (9:132989306 A>G), RS1000696813 (9:132988193 A>C,G,T), RS1000776141 (9:132972063 T>A), RS1000809536 (9:132960373 C>T), RS1000819917 (9:132977560 GAGCAGAC>G), RS1000827024 (9:132974992 C>T), RS1001098523 (9:132948934 G>A), RS1001137015 (9:132960643 T>C), RS1001157967 (9:132984836 C>T), RS1001200466 (9:132993731 G>A)

Disease associations

OMIM: gene MIM:604383 | disease phenotypes: MIM:187900, MIM:191100, MIM:227300, MIM:185050

GenCC curated gene-disease

Disease	Classification	Inheritance
platelet-type bleeding disorder 17	Strong	Autosomal dominant
autosomal dominant macrothrombocytopenia	Supportive	Autosomal dominant
platelet storage pool deficiency	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
platelet-type bleeding disorder 17	Definitive	AD

Mondo (7): platelet-type bleeding disorder 17 (MONDO:0008553), tuberous sclerosis 1 (MONDO:0008612), factor V and factor VIII, combined deficiency of, type 1 (MONDO:0009206), platelet storage pool deficiency (MONDO:0008495), thrombocytopenia (MONDO:0002049), hereditary neoplastic syndrome (MONDO:0015356), autosomal dominant macrothrombocytopenia (MONDO:0015372)

Orphanet (5): Gray platelet syndrome (Orphanet:721), Tuberous sclerosis complex (Orphanet:805), Combined deficiency of factor V and factor VIII (Orphanet:35909), Alpha delta granule deficiency (Orphanet:734), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000421	Epistaxis
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0002239	Gastrointestinal hemorrhage
HP:0003010	Prolonged bleeding time
HP:0003337	Reduced prothrombin consumption
HP:0003593	Infantile onset
HP:0004846	Prolonged bleeding after surgery
HP:0006298	Prolonged bleeding after dental extraction
HP:0008148	Impaired epinephrine-induced platelet aggregation
HP:0008320	Impaired collagen-induced platelet aggregation
HP:0011877	Increased mean platelet volume
HP:0011890	Prolonged bleeding following procedure
HP:0011974	Myelofibrosis
HP:0012526	Absence of alpha granules
HP:0031364	Ecchymosis
HP:0031965	Increased RBC distribution width
HP:0032438	Platelet anisocytosis
HP:0040185	Macrothrombocytopenia
HP:0100608	Metrorrhagia

GWAS associations

89 associations (top):

Study	Trait	p-value
GCST004599_1	Mean platelet volume	2.000000e-107
GCST004599_75	Mean platelet volume	2.000000e-55
GCST004600_81	Eosinophil percentage of white cells	2.000000e-15
GCST004602_76	Mean corpuscular volume	8.000000e-09
GCST004603_47	Platelet count	6.000000e-88
GCST004603_96	Platelet count	7.000000e-28
GCST004606_13	Eosinophil count	4.000000e-11
GCST004606_14	Eosinophil count	6.000000e-22
GCST004607_112	Plateletcrit	6.000000e-27
GCST004610_179	White blood cell count	1.000000e-09
GCST004611_46	High light scatter reticulocyte count	9.000000e-21
GCST004612_102	High light scatter reticulocyte percentage of red cells	1.000000e-22
GCST004613_127	Sum neutrophil eosinophil counts	5.000000e-11
GCST004614_32	Granulocyte count	7.000000e-11
GCST004616_205	Platelet distribution width	4.000000e-40
GCST004617_172	Eosinophil percentage of granulocytes	2.000000e-11
GCST004617_173	Eosinophil percentage of granulocytes	3.000000e-10
GCST004618_78	White blood cell count (basophil)	3.000000e-15
GCST004619_154	Reticulocyte fraction of red cells	5.000000e-22
GCST004619_90	Reticulocyte fraction of red cells	2.000000e-13
GCST004621_131	Red cell distribution width	6.000000e-30
GCST004622_23	Reticulocyte count	5.000000e-19
GCST004622_24	Reticulocyte count	1.000000e-12
GCST004623_128	Neutrophil percentage of granulocytes	3.000000e-12
GCST004624_137	Sum eosinophil basophil counts	7.000000e-11
GCST004624_138	Sum eosinophil basophil counts	7.000000e-26
GCST004626_73	Myeloid white cell count	7.000000e-11
GCST004628_105	Immature fraction of reticulocytes	3.000000e-13
GCST004628_106	Immature fraction of reticulocytes	4.000000e-11
GCST004630_231	Mean corpuscular hemoglobin	1.000000e-12

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0007984	platelet component distribution width
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0009188	Red cell distribution width
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0007992	basophil percentage of leukocytes
EFO:0004251	myeloproliferative disorder
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010981	Platelet Storage Pool Deficiency	C15.378.100.685; C15.378.140.735; C15.378.463.735
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C566060	Thrombasthenia-Thrombocytopenia, Hereditary (supp.)
C565346	Tuberous Sclerosis 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation	2
triphenyl phosphate	affects expression	1
titanium dioxide	decreases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
pomalidomide	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Doxorubicin	decreases response to substance	1
Tretinoin	increases expression	1
Zinc	decreases expression	1
Aflatoxin B1	increases methylation	1
Gold Compounds	increases expression	1
Palmitic Acid	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_HC74	HEK293 eGFP-GFI1B	Transformed cell line	Female
CVCL_QY84	SANi005-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

276 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT