SF3B1

Summary

SF3B1 (splicing factor 3b subunit 1, HGNC:10768) is a protein-coding gene on chromosome 2q33.1, encoding Splicing factor 3B subunit 1 (O75533). Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. In precision oncology, SF3B1 K666N confers sensitivity to Spliceostatin A in Breast Cancer (CIViC Level D); 2 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron’s branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 23451 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC)
• Clinical variants (ClinVar): 98 total — 3 likely-pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 14 cancer types
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_012433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10768
Approved symbol	SF3B1
Name	splicing factor 3b subunit 1
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	SAP155, SF3b155, PRPF10, Prp10, Hsh155
Ensembl gene	ENSG00000115524
Ensembl biotype	protein_coding
OMIM	605590
Entrez	23451

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000335508, ENST00000409915, ENST00000414174, ENST00000414963, ENST00000424674, ENST00000462613, ENST00000468925, ENST00000470268, ENST00000479532, ENST00000482158, ENST00000487698, ENST00000496458, ENST00000652026, ENST00000652738, ENST00000929354, ENST00000929355, ENST00000929356, ENST00000963257, ENST00000963258, ENST00000963259

RefSeq mRNA: 3 — MANE Select: NM_012433 NM_001005526, NM_001308824, NM_012433

CCDS: CCDS33356, CCDS46479, CCDS82550

Canonical transcript exons

ENST00000335508 — 25 exons

Exon	Start	End
ENSE00000784174	197396056	197396328
ENSE00000784199	197420428	197420542
ENSE00000964860	197409770	197410007
ENSE00000964861	197408369	197408581
ENSE00000964862	197407998	197408119
ENSE00000964863	197405275	197405472
ENSE00000964864	197405076	197405177
ENSE00000964865	197403585	197403764
ENSE00000964866	197402949	197403035
ENSE00000964867	197402556	197402826
ENSE00000964868	197401985	197402130
ENSE00000964869	197401742	197401888
ENSE00000964870	197401400	197401525
ENSE00000964871	197400715	197400936
ENSE00000964872	197400252	197400434
ENSE00000964873	197400055	197400166
ENSE00000964874	197398461	197398581
ENSE00000964875	197397985	197398116
ENSE00000964876	197392972	197393188
ENSE00001005134	197423808	197423974
ENSE00001337127	197389784	197392461
ENSE00001858642	197434972	197435028
ENSE00003467095	197418509	197418588
ENSE00003491824	197421029	197421133
ENSE00003518074	197416741	197416911

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 138.0552 / max 2735.9771, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33075	138.0552	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.48	gold quality
ventricular zone	UBERON:0003053	99.43	gold quality
epithelium of nasopharynx	UBERON:0001951	99.38	gold quality
right uterine tube	UBERON:0001302	99.32	gold quality
skin of hip	UBERON:0001554	99.31	gold quality
upper leg skin	UBERON:0004262	99.31	gold quality
superficial temporal artery	UBERON:0001614	99.30	gold quality
left ovary	UBERON:0002119	99.30	gold quality
granulocyte	CL:0000094	99.29	gold quality
body of uterus	UBERON:0009853	99.28	gold quality
right ovary	UBERON:0002118	99.27	gold quality
endocervix	UBERON:0000458	99.25	gold quality
body of pancreas	UBERON:0001150	99.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.25	gold quality
stromal cell of endometrium	CL:0002255	99.22	gold quality
ganglionic eminence	UBERON:0004023	99.22	gold quality
tongue squamous epithelium	UBERON:0006919	99.22	gold quality
calcaneal tendon	UBERON:0003701	99.21	gold quality
mucosa of stomach	UBERON:0001199	99.20	gold quality
tibial nerve	UBERON:0001323	99.20	gold quality
lymph node	UBERON:0000029	99.18	gold quality
left lobe of thyroid gland	UBERON:0001120	99.18	gold quality
spleen	UBERON:0002106	99.17	gold quality
embryo	UBERON:0000922	99.16	gold quality
right lobe of thyroid gland	UBERON:0001119	99.16	gold quality
right lung	UBERON:0002167	99.16	gold quality
parietal pleura	UBERON:0002400	99.16	gold quality
pleura	UBERON:0000977	99.15	gold quality
adenohypophysis	UBERON:0002196	99.15	gold quality
left uterine tube	UBERON:0001303	99.13	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	3.97
E-MTAB-6058	no	691.30
E-MTAB-8559	no	414.79
E-MTAB-8205	no	337.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting SF3B1, 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-23B-5P	99.98	66.07	587
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-5007-5P	97.95	64.71	614
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-924	97.78	66.21	681
HSA-MIR-2277-3P	91.94	62.27	299

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• determined the three-dimensional structure of the human SF3b complex by single-particle electron cryomicroscopy at a resolution of less than 10 angstroms, allowing identification of protein domains with known structural folds (PMID:12738865)
• Multiple U2AF65 binding sites within SF3b155 regulate conformational rearrangements during spliceosome assembly. (PMID:16376933)
• identified SAP155 as an RNA trans-acting factor that binds to CRCE 1, functions to regulate the alternative 5’ splice site selection of Bcl-x pre-mRNA, and is required for ceramide to induce the activation of the Bcl-x(s) 5’ splice site (PMID:16790528)
• We demonstrate that the T. cruzi SF3b155 interface is larger and contains more complex elements than its human counterpart. (PMID:17931603)
• Complex assembly mechanism and an RNA-binding mode of p14-SF3b155 spliceosomal protein complex is identified by NMR solution structure and functional analyses. (PMID:18076038)
• NIPP1 works as a molecular sensor for PP1 to recognize phosphorylated Sap155. (PMID:18842582)
• Puf60-UHM binds to ULM sequences in the splicing factors SF1, U2AF65, and SF3b155. (PMID:18974054)
• SF3B1 may be a potential novel marker in the diagnosis of RARS and in the prediction of SF3B1 may be a potential novel marker in the diagnosis of RARS and in the prediction of thrombotic events in patients with RARS-T. (PMID:21886174)
• Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (PMID:21995386)
• international genetic association studies: Mutations in SF3B1 are strongly associated with a specific disease phenotype (i.e., ring sideroblasts) in myelodysplastic syndromes. SF3B1 mutations are independent predictors of favorable clinical outcome. (PMID:21998214)
• Data indicate that the identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in chronic lymphocytic leukemia (CLL). (PMID:22039264)
• it is conceivable that SF3B1 mutations induce RS formation by downregulating ABCB7 expression (PMID:22064353)
• in a series of MDS patients, the SF3B1 mutation status was not associated with time to AML progression or overall survival (PMID:22064355)
• SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts. (PMID:22096241)
• SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. (PMID:22158541)
• SF3B1 mutations are prevalent in low-risk MDS with ring sideroblasts, SF3B1 mutations are associated with a favorable prognosis. (PMID:22323480)
• Of 63 monoclonal B-cell lymphocytosis patients, only 1 had a SF3B1 K666N mutation. This low prevalence of SF3B1 mutations is consistent with the rarity in this indolent condition of other genetic lesions associated with high-risk CLL. (PMID:22461140)
• Data indicate that altered FIR and c-myc pre-mRNA splicing, in addition to c-Myc expression by augmented FIR/FIRDeltaexon2-SAP155 complex, potentially contribute to colorectal cancer development. (PMID:22496461)
• mutational status of SF3B1 had a prognostic value for CLL that was independent of clinical stage or espression of ZAP70 or CD38 (PMID:22738114)
• Mutations in SF3B1 is associated with myelodysplastic syndromes. (PMID:22826563)
• These data increase our knowledge of the impact of SF3B1 mutations in persons with myelodysplastic syndromes (PMID:22921018)
• results show that refractory anemia with ring sideroblasts and marked thrombocytosis is characterized by high frequencies of SF3B1mut associated with percentages of ring sideroblasts and JAK2V617F correlated with platelet counts (PMID:22929973)
• Novel splicing variants of FIR, Delta3 and Delta4, were also generated by SAP155 siRNA. (PMID:23113893)
• SF3B1 mutations are associated with chronic lymphocytic leukemia. (PMID:23138133)
• biologic and clinical significance of mutations in SF3B1 in myeloid and lymphoid neoplasms (PMID:23160465)
• Clonal evolution from lower to higher risk implicated the emergence of NOTCH1, SF3B1, and BIRC3 abnormalities in addition to TP53 and 11q22-q23 lesions in chronic lymphocytic leukemia. (PMID:23243274)
• data suggest that SF3B1, U2AF1 and SRSF2 mutations occur not only in myeloid lineage tumors but also in lymphoid lineage tumors; data suggest that the splicing gene mutations play important roles in the pathogenesis of hematologic tumors, but rarely in solid tumors (PMID:23280334)
• MDS patients carrying a somatic mutation of SF3B1 have inappropriately low hepcidin levels which may cause excessive reticuloendothelial iron release and parenchymal iron loading. (PMID:23300182)
• Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. (PMID:23313955)
• SRSF2 is the most frequently mutated spliceosome gene in chronic myelomonocytic leukemia, but neither it nor SF3B1 or U2AF35 mutations are prognostically relevant. (PMID:23335386)
• this study reveals subclonal evolution involving cells with SF3B1 mutations in chronic lymphocytic leukemia; the proportionate representation of cells harboring SF3B1 mutations can increase independent of therapy or loss of functional p53 (PMID:23337928)
• SF3B1 mutation is a rare molecular event in Chinese AML and CML patients (PMID:23395771)
• Allogeneic hematopoietic stem cell transplantation can provide long-term disease control in patients with poor-risk chronic lymphocytic leukemia independent of the presence of TP53, SF3B1, and NOTCH1 mutations. (PMID:23435461)
• Studies indicate that NOTCH1 and SF3B1 are the most frequently mutated genes in chronic lymphocytic leukemia (CLL). (PMID:23531595)
• SF3B1 gene mutation is associated with chronic lymphocytic leukemia. (PMID:23558524)
• SF3B1 mutations are associated with chronic lymphocytic leukemia. (PMID:23568491)
• Age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis. (PMID:23594705)
• The interaction between SAP155 and FIR/FIRDeltaexon2 not only integrates cell-cycle progression and c-Myc transcription by modifying P27 and P89 expression. (PMID:23594796)
• Short telomeres were particularly associated with high-risk genetic markers, such as NOTCH1, SF3B1, or TP53 aberrations, and predicted a short time to treatment (TTT) and overall survival (OS) (both P < 0.0001). TL was an independent prognostic factor (PMID:23620080)
• SF3B1 mutations are associated with chronic lymphocytic leukemia. (PMID:23685408)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sf3b1	ENSDARG00000056138
mus_musculus	Sf3b1	ENSMUSG00000025982
rattus_norvegicus	Sf3b1	ENSRNOG00000013516
drosophila_melanogaster	Sf3b1	FBGN0031266
caenorhabditis_elegans		WBGENE00011605

Protein

Protein identifiers

Splicing factor 3B subunit 1 — O75533 (reviewed: O75533)

Alternative names: Pre-mRNA-splicing factor SF3b 155 kDa subunit, Spliceosome-associated protein 155

All UniProt accessions (5): A0A494C1M2, B4DGZ4, O75533, F8WC19, H7C341

UniProt curated annotations — full annotation on UniProt →

Function. Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing. Within the 17S U2 SnRNP complex, SF3B1 is part of the SF3B subcomplex, which is required for ‘A’ complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA. Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the ‘E’ complex. Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs. Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92.

Subunit / interactions. Component of the 17S U2 SnRNP complex, a ribonucleoprotein complex that contains small nuclear RNA (snRNA) U2 and a number of specific proteins. Part of the SF3B subcomplex of the 17S U2 SnRNP complex. SF3B associates with the splicing subcomplex SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Within the SF3B complex, interacts directly (via HEAT domain) with SF3B3, SF3B5, SF3B6 and (via HEAT domain) with PHF5A (PubMed:16432215, PubMed:21062891, PubMed:27720643, Ref.41). The SF3B subcomplex interacts with U2AF2. Identified in the spliceosome C complex. Component of the minor (U12-type spliceosome) spliceosome. Within the minor spliceosome complex, interacts with SCNM1 and CRIPT. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Phosphorylated form interacts with PPP1R8. Interacts with PQBP1. Interacts with RBM17. Interacts with RBM39. Interacts with SETX. Interacts with RBM15. Interacts with USH1G. Interacts with SDE2. Interacts with U2AF1. Interacts with CACTIN. Interacts with ZRSR1. Interacts with CYREN.

Subcellular location. Nucleus. Nucleus speckle.

Post-translational modifications. Phosphorylation occurs concomitantly with the splicing catalytic steps. Phosphorylation on Thr-244, Thr-248 and Thr-313 by cyclin-dependent kinases promotes interaction with PPP1R8 during mitosis. Phosphorylation by CDK11 enables the association between SF3B1 and U5 and U6 snRNAs in the activated spliceosome, thereby promoting spliceosome assembly. Citrullinated by PADI4.

Similarity. Belongs to the SF3B1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75533-1	1	yes
O75533-2	2

RefSeq proteins (3): NP_001005526, NP_001295753, NP_036565* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR015016	SF3b_su1	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR038737	SF3b_su1-like	Family
IPR054573	PP2A/SF3B1-like_HEAT	Domain

Pfam: PF08920, PF22646

UniProt features (190 total): helix 71, modified residue 42, mutagenesis site 21, repeat 11, strand 10, region of interest 9, site 9, turn 4, compositionally biased region 4, cross-link 4, sequence conflict 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

74 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4OZ1	X-RAY DIFFRACTION	1.74
7SN6	X-RAY DIFFRACTION	1.8
6N3E	X-RAY DIFFRACTION	1.89
6N3F	X-RAY DIFFRACTION	2.1
7Q4O	ELECTRON MICROSCOPY	2.1
2PEH	X-RAY DIFFRACTION	2.11
7Q4P	ELECTRON MICROSCOPY	2.15
7Q3L	ELECTRON MICROSCOPY	2.21
3LQV	X-RAY DIFFRACTION	2.38
7B9C	X-RAY DIFFRACTION	2.4
2F9D	X-RAY DIFFRACTION	2.5
7EVO	ELECTRON MICROSCOPY	2.5
7EVN	ELECTRON MICROSCOPY	2.6
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
8HK1	ELECTRON MICROSCOPY	2.7
7DVQ	ELECTRON MICROSCOPY	2.89
2F9J	X-RAY DIFFRACTION	3
7B0I	X-RAY DIFFRACTION	3
7B91	X-RAY DIFFRACTION	3
7B92	X-RAY DIFFRACTION	3
7OMF	X-RAY DIFFRACTION	3
7VPX	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
6EN4	X-RAY DIFFRACTION	3.08
5IFE	X-RAY DIFFRACTION	3.1
7ONB	ELECTRON MICROSCOPY	3.1
7OPI	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75533-F1	75.53	0.45

Functional residue map

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

Catalytic / active sites (9): 469 (interaction with rna); 587 (interaction with rna); 592 (interaction with phf5a); 602 (interaction with sf3b3); 677 (interaction with sf3b3); 1035 (interaction with rna); 1049 (interaction with rna); 1141 (interaction with rna); 1205 (interaction with sf3b3)

Post-translational modifications (46): 125, 129, 141, 142, 157, 194, 203, 207, 211, 214, 223, 227, 229, 235, 244, 248, 257, 261, 267, 273 …

Mutagenesis-validated functional residues (21):

Position	Phenotype
313	no effect on interaction with ppp1r8.
338	abolishes interaction with rbm39; when associated with a-200; a-218; a-232; a-254; a-293 and a-310.
700	does not affect the stability of the sf3b complex interaction with u2af65. does not decrease the affinity to rna.
200	abolishes interaction with rbm39; when associated with a-218; a-232; a-254; a-293; a-310 and a-338.
218	abolishes interaction with rbm39; when associated with a-200; a-232; a-254; a-293; a-310 and a-338.
223	no effect on interaction with ppp1r8.
227	no effect on interaction with ppp1r8.
232	abolishes interaction with rbm39; when associated with a-200; a-218; a-254; a-293; a-310 and a-338.
235	no effect on interaction with ppp1r8.
244	slight inhibition of interaction with ppp1r8.
248	slight inhibition of interaction with ppp1r8.
254	abolishes interaction with rbm39; when associated with a-200; a-218; a-232; a-293; a-310 and a-338.
257	no effect on interaction with ppp1r8.
261	slight inhibition of interaction with ppp1r8.
267	no effect on interaction with ppp1r8.
273	no effect on interaction with ppp1r8.
278	no effect on interaction with ppp1r8.
293	abolishes interaction with rbm39; when associated with a-200; a-218; a-232; a-254; a-310 and a-338.
296	no effect on interaction with ppp1r8.
303	no effect on interaction with ppp1r8.
310	abolishes interaction with rbm39; when associated with a-200; a-218; a-232; a-254; a-293 and a-338.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 324 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, MITSIADES_RESPONSE_TO_APLIDIN_DN, ATGTTAA_MIR302C, MAHAJAN_RESPONSE_TO_IL1A_DN, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, MODULE_239, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GRE_C, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING

GO Biological Process (10): spliceosomal complex assembly (GO:0000245), RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), chromatin remodeling (GO:0006338), RNA splicing (GO:0008380), positive regulation of transcription by RNA polymerase I (GO:0045943), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription by RNA polymerase III (GO:0045945), U2-type prespliceosome assembly (GO:1903241), mRNA processing (GO:0006397)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), splicing factor binding (GO:1990935), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U2-type spliceosomal complex (GO:0005684), U2 snRNP (GO:0005686), U12-type spliceosomal complex (GO:0005689), nucleolus (GO:0005730), nuclear speck (GO:0016607), U11/U12 snRNP (GO:0034693), U2-type prespliceosome (GO:0071004), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013), B-WICH complex (GO:0110016), chromatin (GO:0000785), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
mRNA Splicing	2
Positive epigenetic regulation of rRNA expression	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
CHD chromatin remodelers	1
Gene expression (Transcription)	1
Epigenetic regulation of gene expression	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	3
spliceosomal complex	3
RNA processing	2
nuclear lumen	2
cellular anatomical structure	2
spliceosomal snRNP complex	2
U2-type spliceosomal complex	2
U1 snRNP	2
U2 snRNP	2
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
chromatin organization	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of transcription by RNA polymerase III	1
transcription by RNA polymerase III	1
spliceosomal complex assembly	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
prespliceosome	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
Prp19 complex	1
U5 snRNP	1
catalytic complex	1
nucleolus	1
SWI/SNF superfamily-type complex	1

Protein interactions and networks

STRING

3371 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SF3B1	SF3B2	Q13435	996
SF3B1	SF3B4	Q15427	995
SF3B1	PHF5A	Q7RTV0	994
SF3B1	SF3B3	Q15393	994
SF3B1	SF3B6	Q9Y3B4	981
SF3B1	U2AF2	P26368	980
SF3B1	SF3A2	Q15428	974
SF3B1	SF3B5	Q9BWJ5	973
SF3B1	RBM17	Q96I25	957
SF3B1	PPP6R1	Q9UPN7	924
SF3B1	PPP6R2	O75170	923
SF3B1	PPP1R8	Q12972	913
SF3B1	PPP6R3	Q5H9R7	882
SF3B1	PUF60	Q9UHX1	879
SF3B1	U2AF1	Q01081	843

IntAct

332 interactions, top by confidence:

A	B	Type	Score
RBM17	SF3B1	psi-mi:“MI:0407”(direct interaction)	0.910
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
PIGS	GPAA1	psi-mi:“MI:0914”(association)	0.760
CCDC97	SF3B1	psi-mi:“MI:0914”(association)	0.730
PHF5A	SF3B1	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
COMMD6	VPS26C	psi-mi:“MI:0914”(association)	0.640
DNAJC8	SF3B1	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SF3B4	SF3B1	psi-mi:“MI:0914”(association)	0.610
DDX41	SF3B1	psi-mi:“MI:0914”(association)	0.600
PPP4R2	SF3B1	psi-mi:“MI:0914”(association)	0.570
PPP4R2	SF3B1	psi-mi:“MI:2364”(proximity)	0.570
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
SF3B1	RPL23A	psi-mi:“MI:0915”(physical association)	0.560
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530

BioGRID (879): SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS), SF3B1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA8, A1A535, A1A5P5, E7F187, O14617, O17237, O18178, O54774, O57683, O75533, P54362, Q08951, Q10178, Q10428, Q13362, Q13367, Q14738, Q14D04, Q28651, Q28653, Q2KI89, Q32PG1, Q4FZZ1, Q54WN0, Q5PQS3, Q5R629, Q5TYV4, Q5U245, Q5VZ89, Q60996, Q61QK6, Q755A1, Q759E2, Q7Z3E5, Q7ZYV9, Q80X82, Q865S1, Q8CIM8, Q8L7A9, Q8MSU4

Diamond homologs: O57683, O75533, P49955, Q10178, Q99NB9

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
DYRK1A	unknown	SF3B1	phosphorylation
CyclinE/CDK2	up-regulates	SF3B1	phosphorylation
CyclinE/CDK2	unknown	SF3B1	phosphorylation
SF3B1	up-regulates	Proliferation
SF3B1	up-regulates	Differentiation
SF3B1	“form complex”	SF3b	binding
SF3B1	“form complex”	“B-WICH complex”	binding
SF3B1	“form complex”	“U2 snRNP complex”	binding
CDK2	up-regulates	SF3B1	phosphorylation
CDK2	unknown	SF3B1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 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
Metabolism of non-coding RNA	8	33.8×	2e-09
mRNA Splicing - Minor Pathway	15	22.4×	6e-15
mRNA Splicing	29	21.2×	7e-29
mRNA Polyadenylation	32	18.7×	6e-30
CHD1 and CHD2 subfamily	24	17.4×	1e-21
Processing of Capped Intron-Containing Pre-mRNA	30	16.4×	2e-26
SARS-CoV-2 modulates host translation machinery	11	16.4×	3e-09
mRNA Splicing - Major Pathway	42	15.3×	6e-36

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	17	56.7×	1e-24
spliceosomal complex assembly	9	29.0×	4e-09
regulation of mRNA splicing, via spliceosome	6	28.5×	6e-06
RNA splicing, via transesterification reactions	8	26.7×	7e-08
mRNA cis splicing, via spliceosome	5	26.5×	9e-05
spliceosomal snRNP assembly	8	24.9×	1e-07
mRNA splicing, via spliceosome	35	17.1×	2e-30
RNA splicing	28	13.2×	6e-21

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

SF3B1 mutations have been described in several myeloid malignancies, predominantly myelodysplastic syndromes (MDS), as well as other hematologic malignancies, breast cancer, and uveal melanoma (UM). SF3B1 is one of several genes involved in RNA splicing that has been identified as recurrently mutated in MDS and other malignanices. The mutations affecting SF3B1 are typically heterozygous, point mutations suspected to be functionally deleterious with R625 and K700E described as a major mutation hotspots. MDS patients with SF3B1 mutations have been reported to have better overall and event-free survival than their wildtype counterparts. Additionally, these mutations are highly associated with subtypes of MDS characterized by ringed sideroblasts (refractory anemia with ringed sideroblasts and refractory cytopenia with multilineage dysplasia and ring sideroblasts). In UM patients, SF3B1 mutations have been reported to be associated with chromosome 3 disomy, which defines a subgroup with low risk of metastasis.

From intOGen — cancer-driver classification: activating (oncogene-like) across 14 cancer types — AML, BLCA, BRCA, CHOL, CLLSLL, HCC, LUNG, MBL, MEL, PAAD, PCM, PRAD…(+2 more).

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	47
Likely benign	6
Benign	12

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
376005	NM_012433.4(SF3B1):c.1998G>C (p.Lys666Asn)	Likely pathogenic
376534	NM_012433.4(SF3B1):c.1874G>A (p.Arg625His)	Likely pathogenic
4278404	NM_012433.4(SF3B1):c.1866G>C (p.Glu622Asp)	Likely pathogenic

SpliceAI

3583 predictions. Top by Δscore:

Variant	Effect	Δscore
2:197393187:CT:C	acceptor_gain	1.0000
2:197393188:TC:T	acceptor_loss	1.0000
2:197393189:C:CA	acceptor_loss	1.0000
2:197393189:C:CC	acceptor_gain	1.0000
2:197393190:T:A	acceptor_loss	1.0000
2:197396051:CTTA:C	donor_loss	1.0000
2:197396052:TTACC:T	donor_loss	1.0000
2:197396053:TAC:T	donor_loss	1.0000
2:197396054:A:AC	donor_gain	1.0000
2:197396055:C:CC	donor_gain	1.0000
2:197396055:C:G	donor_loss	1.0000
2:197396055:CCT:C	donor_gain	1.0000
2:197396055:CCTA:C	donor_gain	1.0000
2:197396055:CCTAT:C	donor_gain	1.0000
2:197396324:GAGGG:G	acceptor_gain	1.0000
2:197396326:GGG:G	acceptor_gain	1.0000
2:197396327:GG:G	acceptor_gain	1.0000
2:197396328:GCTGA:G	acceptor_loss	1.0000
2:197396329:C:CC	acceptor_gain	1.0000
2:197396329:C:T	acceptor_loss	1.0000
2:197396330:T:G	acceptor_loss	1.0000
2:197397987:AATGG:A	donor_gain	1.0000
2:197398455:GCTTA:G	donor_loss	1.0000
2:197398456:CTTAC:C	donor_loss	1.0000
2:197398457:TTA:T	donor_loss	1.0000
2:197398458:TA:T	donor_loss	1.0000
2:197398459:A:AC	donor_gain	1.0000
2:197398460:C:CC	donor_gain	1.0000
2:197398460:C:CT	donor_loss	1.0000
2:197398460:CCTGT:C	donor_gain	1.0000

AlphaMissense

8531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:197392408:G:C	N1270K	1.000
2:197392408:G:T	N1270K	1.000
2:197392432:T:A	R1262S	1.000
2:197392432:T:G	R1262S	1.000
2:197392433:C:A	R1262I	1.000
2:197392433:C:G	R1262T	1.000
2:197392436:A:T	V1261D	1.000
2:197392445:G:T	A1258D	1.000
2:197392451:T:C	H1256R	1.000
2:197392452:G:C	H1256D	1.000
2:197392460:C:T	G1253D	1.000
2:197392461:C:G	G1253R	1.000
2:197393021:C:T	G1236D	1.000
2:197393022:C:G	G1236R	1.000
2:197393053:A:C	H1225Q	1.000
2:197393053:A:T	H1225Q	1.000
2:197393054:T:C	H1225R	1.000
2:197393055:G:C	H1225D	1.000
2:197393055:G:T	H1225N	1.000
2:197393060:G:A	S1223F	1.000
2:197393074:A:C	N1218K	1.000
2:197393074:A:T	N1218K	1.000
2:197393082:A:G	W1216R	1.000
2:197393082:A:T	W1216R	1.000
2:197393089:G:C	N1213K	1.000
2:197393089:G:T	N1213K	1.000
2:197393135:C:T	G1198E	1.000
2:197393136:C:A	G1198W	1.000
2:197393136:C:G	G1198R	1.000
2:197393136:C:T	G1198R	1.000

dbSNP variants (sampled 300 via entrez): RS1000022158 (2:197428301 T>A), RS1000031555 (2:197390201 A>G), RS1000044158 (2:197395206 A>G,T), RS1000083472 (2:197389861 A>G), RS1000117267 (2:197433602 T>C), RS1000460254 (2:197403472 A>G,T), RS1000470217 (2:197426636 A>G), RS1000489502 (2:197433919 T>A,C), RS1000520425 (2:197423295 G>A), RS1000533965 (2:197400246 G>A), RS1000564107 (2:197411043 T>A), RS1000622759 (2:197416689 A>C,G), RS1000650074 (2:197399979 G>C), RS1000655389 (2:197416417 G>A), RS1000721294 (2:197407770 T>A,C)

Disease associations

OMIM: gene MIM:605590 | disease phenotypes: MIM:614286, MIM:608232, MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (5): myelodysplastic syndrome (MONDO:0018881), neurodevelopmental disorder (MONDO:0700092), chronic myeloid leukemia (MONDO:0011996), acute myeloid leukemia (MONDO:0018874), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): Myelodysplastic syndrome (Orphanet:52688), Chronic myeloid leukemia (Orphanet:521), Acute myeloid leukemia (Orphanet:519)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000539	Abnormality of refraction
HP:0000541	Retinal detachment
HP:0000572	Visual loss
HP:0000980	Pallor
HP:0001098	Abnormal fundus morphology
HP:0001231	Abnormal fingernail morphology
HP:0001442	Typified by somatic mosaicism
HP:0001635	Congestive heart failure
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001892	Abnormal bleeding
HP:0001894	Thrombocytosis
HP:0001895	Normochromic anemia
HP:0001897	Normocytic anemia
HP:0001913	Decreased total granulocyte count
HP:0001931	Hypochromic anemia
HP:0001974	Increased total leukocyte count
HP:0002240	Hepatomegaly
HP:0002863	Myelodysplasia
HP:0004808	Acute myeloid leukemia
HP:0004828	Refractory anemia with ringed sideroblasts
HP:0005513	Increased megakaryocyte count
HP:0005528	Bone marrow hypocellularity
HP:0007902	Vitreous hemorrhage
HP:0007906	Ocular hypertension
HP:0008494	Inferior lens subluxation
HP:0010920	Zonular cataract
HP:0010972	Anemia of inadequate production

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1229013 (SINGLE PROTEIN), CHEMBL3885592 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items; also 7 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
SF3B1 K666N	Spliceostatin A	Breast Cancer	Sensitivity/Response	CIViC D	EID1418
SF3B1 K700E	Etoposide + Olaparib	Leukemia	Sensitivity/Response	CIViC D	EID10139
SF3B1 K700E	Spliceostatin A	Breast Cancer	Sensitivity/Response	CIViC D	EID1417

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.55	Kd	2847	nM	CHEMBL3752910
5.55	ED50	2847	nM	CHEMBL3752910
5.52	Kd	3001	nM	CHEMBL5653589
5.52	ED50	3001	nM	CHEMBL5653589
5.12	Kd	7501	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 33 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149385: Binding affinity to human SF3B1 incubated for 45 mins by Kinobead based pull down assay	kd	2.8474	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149385: Binding affinity to human SF3B1 incubated for 45 mins by Kinobead based pull down assay	kd	3.0008	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179101: Binding affinity against SF3B1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	7.5010	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects splicing, decreases expression, affects cotreatment, increases abundance	3
trichostatin A	affects cotreatment, decreases expression	2
Arsenic	increases expression, affects splicing, affects cotreatment, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
quercitrin	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	affects phosphorylation	1
hinokiflavone	increases sumoylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
qinghuang	affects response to substance	1
bisphenol AF	increases expression	1
Acetaminophen	decreases expression	1
Arbutin	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4201370	Binding	Binding affinity to SAP155 in human GM18453 cells harboring NPC1 mutant assessed as restoration of cholesterol trafficking at 50 nM after 48 hrs by filipin-staining based fluorescence microscopic analysis	GEX1A, a Polyketide from Streptomyces chromofuscus, Corrects the Cellular Defects Associated with Niemann-Pick Type C1 in Human Fibroblasts. — J Nat Prod

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C301	Mel202	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00117507	PHASE4	COMPLETED	Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients
NCT00202371	PHASE4	WITHDRAWN	Transfusion Effects in Myelodysplastic Patients: Limiting Exposure
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00452660	PHASE4	COMPLETED	Evaluation the Effect of Exjade on Oxidative Stress in Low Risk Myelodysplastic Syndrome Patients With Iron Over Load
NCT00481143	PHASE4	COMPLETED	Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndrome and Transfusion-dependent Iron Overload
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488436	PHASE4	COMPLETED	Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome
NCT00564941	PHASE4	COMPLETED	Evaluating the Efficacy of Deferasirox in Transfusion Dependent Chronic Anaemias (Myelodysplastic Syndrome, Beta-thalassaemia Patients) With Chronic Iron Overload
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT01011283	PHASE4	TERMINATED	To Demonstrate Superiority of Decitabine Over Azacitidine in Subjects With Intermediate- or High-risk MDS.
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01201811	PHASE4	COMPLETED	Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)
NCT01250951	PHASE4	COMPLETED	This Study Will Evaluate Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndromes (MDS), Thalassemia and Rare Anemia Types Having Transfusion-induced Iron Overload.
NCT01326845	PHASE4	TERMINATED	Myelodysplastic Syndrome (MDS) Gastrointestinal (GI) Tolerability Study
NCT01339988	PHASE4	UNKNOWN	Busulfan and Cyclophosphamide Instead of Total Boby Irradiation (TBI) and Cyclophosphamide for Hematological Malignancies Hematocrit (HCT)
NCT02013102	PHASE4	UNKNOWN	A Phase Ⅳ Study of Decitabine in Myelodysplastic Syndrome
NCT02145026	PHASE4	COMPLETED	A Study of Epoetin Beta Treatment in Anemic Participants With Myelodysplastic Syndrome (MDS)
NCT02875743	PHASE4	COMPLETED	King’s Invasive Aspergillosis Study II
NCT03176849	PHASE4	COMPLETED	A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT
NCT03335943	PHASE4	UNKNOWN	Myelodysplastic Syndrome–CDA-2 Hematological Improvement National Affirmation Study
NCT03598582	PHASE4	COMPLETED	Biological Predictive Factors of Response to ESA in Low Risk MDS Patients
NCT06004765	PHASE4	UNKNOWN	Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS
NCT06006949	PHASE4	UNKNOWN	Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory MDS-RS
NCT00000591	PHASE3	COMPLETED	T-Cell Depletion in Unrelated Donor Marrow Transplantation
NCT00002517	PHASE3	COMPLETED	Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00002742	PHASE3	COMPLETED	Antifungal Therapy for Fever and Neutropenia in Patients Receiving Treatment for Hematologic Cancer
NCT00002798	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
NCT00002926	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00002989	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Idarubicin and Peripheral Stem Cell Transplantation in Treating Patients With Leukemia or Myelodysplastic Syndrome
NCT00003138	PHASE3	COMPLETED	Erythropoietin (EPO)+/- Filgrastim (G-CSF) vs. Supportive Therapy Alone for Patients With Myelodysplastic Syndromes
NCT00003436	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia
NCT00003593	PHASE3	COMPLETED	Chemotherapy in Treating Children With Down Syndrome and Myeloproliferative Disorder, Acute Myelogenous Leukemia, or Myelodysplastic Syndrome
NCT00003602	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
NCT00003687	PHASE3	COMPLETED	Treatment for Chronic Pain in Patients With Advanced Cancer
NCT00003805	PHASE3	COMPLETED	Prevention of Infection in Patients With Hematologic Cancer and Persistent Fever Caused by a Low White Blood Cell Count
NCT00004208	PHASE3	COMPLETED	Antithymocyte Globulin and Cyclosporine in Treating Patients With Myelodysplastic Syndrome
NCT00005805	PHASE3	COMPLETED	St. John’s Wort in Relieving Fatigue in Patients Undergoing Chemotherapy or Hormone Therapy for Cancer
NCT00005823	PHASE3	COMPLETED	Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
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