Table 1.
Known bone marrow failure and/or hematological malignancy predisposition transcription factors.
| TF Groups | Gene symbol |
Germline HM gene |
Germline blood disorder gene | Canonical Transcript Coding size (aa) |
TF Family | DNA binding motif | Human phenotype | Role in hematopoiesis (downstream differentiation) | Target genes | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| OMIM | Mondo | ENCODE and ChEA Consensus TFs from ChIP-X | |||||||||
| Reported phenotype | Zygosity | Reported Phenotype # | |||||||||
| Best characterized BMF/HM genes | RUNX1 | Yes | Yes | 480 | RUNX | TGTGG | AML Platelet disorder |
AD | AML hereditary thrombocytopenia B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1) |
HSC, CMP, Megakaryocyte, Platelet, B-cell, T-cell | GATA2, GATA1, MAX, BRCA1, TCF3, CREB1, UBTF, TAF1, ZBTB7A |
| CEBPA | Yes | No | 358 | bZIP | CCAAT T(T/G)NNGNAA(T/G) |
AML | AD | AML | Granulocyte, Eosinophil, Monocyte, Neutrophil | ATF2, CREB1, CIN3A, CEBPD, NFYA, CREB1, NFYB, SIX5, GABPA | |
| GATA2 | Yes | Yes | 480 | GATA | (A/T)GATA(A/G) | Emberger syndrome Immunodeficiency 21 AML MDS |
AD | MDS/AML deafness-lymphedema-leukemia syndrome monocytopenia with susceptibility to infections |
HSC, Mast cell, Erythrocyte, Basophil, Megakaryocyte | GATA1, RUNX1, SMAD4, TP63, NFE2L2, PPARG, UBTF, SPI1, RCOR1 | |
| PAX5, MECOM, GATA1 and STAT3 BMF/HM genes | PAX5 | Yes | No | 391 | PAX | GGCTGAG | ALL | AD | ALL | Myeloid/lymphoid progenitor), B-cell | Not included in dataset |
|
MECOM
(MDS1/ EVI1) |
Yes | Yes | 1239 | ZF | AAGA(C/T)AAGATAA | Radioulnar synostosis with amegakaryoctiyc thrombocytopenia | AD | AML MECOM-associated syndrome radioulnar synostosis with amegakaryyocytic thrombocytopenia |
HSC | SPI1, RUNX1, GATA1, GATA2, FLI1, ZNF384, FOS, RCOR1, TCF3 | |
| STAT3 | Yes | Yes | 770 | STAT | TTCC(C/G)GGAA | Autoimmune disease Hyper-IgE recurrent infection syndrome |
AD AR |
STAT3-related early-onset multisystem autoimmune disease hyper-IgE recurrent infection syndrome 1 |
HSC HPC |
AR, SMAD4, SUZ12, REST, TCF3, SOX2, POU5F1, NFE2L2, NANOG | |
| GATA1 | Yes | Yes | 413 | GATA | (A/T)GATA(A/G) | Anemia Hemolytic anemia Leukemia Thrombocytopenia with beta-thalassemia Thrombocytopenia with/without dyserythropoeitic anemia |
XLR | GATA1-Related X-Linked Cytopenia AML thrombocytopenia transient myeloproliferative syndrome |
Eosinophil, Platelet, RBC Basophil, Mast-cell, Erythrocytes, Dendritic cell, Megakaryocyte, Macrophage, MPC |
GATA2, RUNX1, SMAD4, AR, ZBTB7A, SPI1, UBTF, ESR1, STAT3 | |
|
ETS BMF/HM
genes |
ETV6
(TEL) |
Yes | Yes | 452 | ETS | (G/C)CGGAAGT(G/A) | AML Thrombocytopenia |
AD | Otosclerosis | HSC Megakaryocyte |
Not included in dataset |
| FLI1 | No | Yes | 452 | ETS | AGGAA(G/A) | Bleeding disorder | AR AD |
Nephronophthisis, Thrombocytopenia, Otosclerosis, paragangliomas, anencephaly, odontochondrodysplasia, schizophrenia, trigonocephaly, thrombocythemia, chondrocalcinosis | Platelet | FLI1, ELF1, SPI1, TAF1, ATF2, RUNX1, BRCA1, CREB1, NRF1 | |
|
IKAROS
BMF/HM genes |
IKZF1 | Yes | Yes | 519 | IKAROS | GGAAA | Immunodeficiency | AD | No Phenotypes reported | T-cell, HSC, CLP | ZKSCAN1, VDR, RCOR1, REST, SUZ12, NFE2L2, SPI1, UBTF |
| IKZF3 | Yes | Yes | 509 | IKAROS | (T/G)GGAA | Immunodeficiency | AD | No Phenotypes reported | B-cell, T-cell | Not included in data set | |
| IKZF5 | No | Yes | 419 | IKAROS | GNNTGTNG | Thrombocytopenia | AD | No Phenotypes reported | HSC | Not included in data set | |
Germline HM and/or blood disorder predisposition genes, found in high evidence Genomics England PanelApp panels: Hematological malignancies cancer susceptibility [Version 3.3] and/or Bleeding and Platelet Disorders [Version 1.16] as well as Cytopenias and congenital anemias [Version 1.111]. Known interacting partners were collated through STRING (12), target genes through ChEA from Chip-X (13), and roles in hematopoiesis literature (14–24). Autosomal dominant, AD; Autosomal recessive, AR.