SF3B2

Summary

SF3B2 (splicing factor 3b subunit 2, HGNC:10769) is a protein-coding gene on chromosome 11q13.1, encoding Splicing factor 3B subunit 2 (Q13435). Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes subunit 2 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. Subunit 2 associates with pre-mRNA upstream of the branch site at the anchoring site. Subunit 2 also interacts directly with subunit 4 of the splicing factor 3b complex. Subunit 2 is a highly hydrophilic protein with a proline-rich N-terminus and a glutamate-rich stretch in the C-terminus.

Source: NCBI Gene 10992 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 25
• Clinical variants (ClinVar): 231 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10769
Approved symbol	SF3B2
Name	splicing factor 3b subunit 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SAP145, SF3b1, Cus1, SF3b145
Ensembl gene	ENSG00000087365
Ensembl biotype	protein_coding
OMIM	605591
Entrez	10992

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 25 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000322535, ENST00000524475, ENST00000524627, ENST00000525207, ENST00000526653, ENST00000528302, ENST00000529577, ENST00000529994, ENST00000530322, ENST00000530981, ENST00000531041, ENST00000531589, ENST00000533421, ENST00000533595, ENST00000534307, ENST00000534765, ENST00000893571, ENST00000893572, ENST00000893573, ENST00000893574, ENST00000934115, ENST00000934116, ENST00000934117, ENST00000934118, ENST00000934119, ENST00000934120, ENST00000934121, ENST00000934122, ENST00000943470, ENST00000943471, ENST00000943472, ENST00000943473, ENST00000943474, ENST00000943475

RefSeq mRNA: 1 — MANE Select: NM_006842 NM_006842

CCDS: CCDS31612

Canonical transcript exons

ENST00000322535 — 22 exons

Exon	Start	End
ENSE00000734590	66055076	66055315
ENSE00000734592	66055535	66055585
ENSE00000734596	66057266	66057375
ENSE00000734599	66058314	66058405
ENSE00000734600	66058830	66059045
ENSE00000734605	66060582	66060731
ENSE00000734606	66061686	66061775
ENSE00000734607	66061891	66061998
ENSE00000734608	66063009	66063116
ENSE00000734609	66063400	66063542
ENSE00000734610	66063628	66063729
ENSE00000734611	66067946	66068045
ENSE00000734612	66068148	66068333
ENSE00000864187	66056838	66056955
ENSE00001292154	66052364	66052517
ENSE00002152522	66068674	66069308
ENSE00003470384	66058054	66058150
ENSE00003567128	66059201	66059338
ENSE00003576414	66059782	66060009
ENSE00003628106	66059515	66059595
ENSE00003636369	66053027	66053104
ENSE00003691548	66052673	66052719

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 154.1888 / max 850.2774, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115275	151.6619	1827
115276	0.9255	562
115279	0.7239	384
115277	0.3556	176
115280	0.2703	107
115278	0.2517	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.91	gold quality
left testis	UBERON:0004533	98.91	gold quality
right testis	UBERON:0004534	98.89	gold quality
adenohypophysis	UBERON:0002196	98.87	gold quality
right uterine tube	UBERON:0001302	98.82	gold quality
ganglionic eminence	UBERON:0004023	98.74	gold quality
right lobe of thyroid gland	UBERON:0001119	98.67	gold quality
left lobe of thyroid gland	UBERON:0001120	98.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.66	gold quality
pituitary gland	UBERON:0000007	98.64	gold quality
cerebellar hemisphere	UBERON:0002245	98.63	gold quality
cerebellar cortex	UBERON:0002129	98.60	gold quality
body of uterus	UBERON:0009853	98.56	gold quality
left ovary	UBERON:0002119	98.55	gold quality
cortical plate	UBERON:0005343	98.55	gold quality
right ovary	UBERON:0002118	98.48	gold quality
endocervix	UBERON:0000458	98.47	gold quality
tibial nerve	UBERON:0001323	98.43	gold quality
tendon of biceps brachii	UBERON:0008188	98.42	gold quality
sural nerve	UBERON:0015488	98.39	gold quality
popliteal artery	UBERON:0002250	98.37	gold quality
tibial artery	UBERON:0007610	98.37	gold quality
body of pancreas	UBERON:0001150	98.36	gold quality
thyroid gland	UBERON:0002046	98.36	gold quality
skin of leg	UBERON:0001511	98.35	gold quality
ectocervix	UBERON:0012249	98.35	gold quality
ascending aorta	UBERON:0001496	98.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.33	gold quality
aorta	UBERON:0000947	98.31	gold quality
thoracic aorta	UBERON:0001515	98.31	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting SF3B2, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-581	98.39	67.42	835
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-6895-5P	97.05	64.96	522
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-4512	95.26	63.08	371
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-1296-5P	93.94	67.71	305
HSA-MIR-4734	88.28	63.44	87

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 9)

• Data show that Vpr induces checkpoint activation and G(2) arrest by binding to the CUS1 domain of SAP145 and interfering with the functions of the SAP145 and SAP49 proteins, two subunits of the multimeric splicing factor 3b (SF3b). (PMID:16923959)
• Inhibiting the induction of two proteins involved in two of the most significantly upregulated cellular processes, ribosome biogenesis (eIF6) and hnRNA splicing (SF3B2/SF3B4), showed that human T cells can enter the cell cycle without growing in size. (PMID:22415777)
• High SF3B2 expression is associated with hepatocellular carcinoma. (PMID:25731616)
• Although amino acid substitutions of residues surrounding Arg-508 had no great effect on PRMT9 recognition of SF3B2, moving the arginine residue within this sequence abolished methylation. (PMID:25979344)
• a docking model based on NOESY measurements suggests that residues 607-616 of the SF3b145 fragment adopt a helical structure that binds to RRM1 predominantly via alpha1, consequently exhibiting a helix-helix interaction in almost antiparallel. (PMID:27862552)
• Splicing complex SF3B depletion impairs DNA end resection and hampers homologous recombination repair. SF3B controls CtIP function at, as least, two levels: by affecting CtIP mRNA levels and controlling CtIP recruitment to DNA breaks, in a way that requires ATM-mediated phosphorylation of SF3B2 at serine 289. (PMID:29705135)
• SF3B2 is a critical determinant of AR-V7 expression and is correlated with aggressive cancer phenotypes. Pladienolide B, an inhibitor of a splicing modulator of the SF3b complex, suppressed the growth of tumors addicted to high SF3B2 expression. SF3B2 is a critical determinant of RNA splicing and gene expression patterns and controls the expression of key genes associated with CRPC progression, such as AR-V7. (PMID:31431456)
• G-quadruplex-forming nucleic acids interact with splicing factor 3B subunit 2 and suppress innate immune gene expression. (PMID:33290632)
• Haploinsufficiency of SF3B2 causes craniofacial microsomia. (PMID:34344887)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sf3b2	ENSDARG00000018049
mus_musculus	Sf3b2	ENSMUSG00000024853
rattus_norvegicus	Sf3b2	ENSRNOG00000020412
caenorhabditis_elegans		WBGENE00021004

Protein

Protein identifiers

Splicing factor 3B subunit 2 — Q13435 (reviewed: Q13435)

Alternative names: Pre-mRNA-splicing factor SF3b 145 kDa subunit, Spliceosome-associated protein 145

All UniProt accessions (7): Q13435, E9PIL8, E9PJ04, E9PJT3, E9PPJ0, H0YCG1, H0YEX5

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, SF3B2 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.

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 with SF3B4. Found in a complex with PRMT9, SF3B2 and SF3B4. Interacts (Arg-508-methylated form) with SMN1 (via Tudor domain). Interacts with RBM7. Interacts with ERCC6. Component of the minor spliceosome. Within this complex, interacts with SCNM1 and CRIPT. (Microbial infection) Interacts with HIV-1 Vpr.

Subcellular location. Nucleus. Nucleus speckle.

Post-translational modifications. Methylation at Arg-508 by PRMT9 is required for the interaction with SMN1.

Disease relevance. Craniofacial microsomia 1 (CFM1) [MIM:164210] A form of craniofacial microsomia, a disorder characterized by a spectrum of craniofacial malformations ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. CFM1 is an autosomal dominant form characterized by mandibular hypoplasia, microtia, facial and preauricular skin tags, epibulbar dermoids, and lateral oral clefts. Affected individuals also present skeletal and cardiac abnormalities. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_006833* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR006568	PSP_pro-rich	Domain
IPR007180	DUF382	Domain
IPR052584	U2_snRNP_Complex_Component	Family

Pfam: PF02037, PF04037, PF04046

UniProt features (95 total): modified residue 20, helix 16, mutagenesis site 13, compositionally biased region 12, cross-link 10, region of interest 7, turn 7, strand 3, sequence variant 2, sequence conflict 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

50 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7Q4O	ELECTRON MICROSCOPY	2.1
7Q4P	ELECTRON MICROSCOPY	2.15
7Q3L	ELECTRON MICROSCOPY	2.21
7EVO	ELECTRON MICROSCOPY	2.5
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
8HK1	ELECTRON MICROSCOPY	2.7
7DVQ	ELECTRON MICROSCOPY	2.89
7VPX	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
7ONB	ELECTRON MICROSCOPY	3.1
7QTT	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
9ZE2	ELECTRON MICROSCOPY	3.26
6QX9	ELECTRON MICROSCOPY	3.28
8I0U	ELECTRON MICROSCOPY	3.3
6FF4	ELECTRON MICROSCOPY	3.4
8I0P	ELECTRON MICROSCOPY	3.4
9ZE0	ELECTRON MICROSCOPY	3.43
9ZEC	ELECTRON MICROSCOPY	3.61
6AHD	ELECTRON MICROSCOPY	3.8
9ZE3	ELECTRON MICROSCOPY	3.93
9ZED	ELECTRON MICROSCOPY	3.94
6Y50	ELECTRON MICROSCOPY	4.1
8QZS	ELECTRON MICROSCOPY	4.1
8I0S	ELECTRON MICROSCOPY	4.2
8R09	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13435-F1	66.49	0.14

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 (30): 222, 245, 247, 275, 289, 298, 307, 309, 311, 317, 360, 362, 431, 435, 436, 508, 508, 515, 780, 861 …

Mutagenesis-validated functional residues (13):

Position	Phenotype
471	does not affect methylation by prmt9.
495	does not affect methylation by prmt9.
502	does not affect methylation by prmt9.
506	does not affect methylation by prmt9; when associated with a-510.
507	moderately diminished formation of omega-n monomethylarginine but greatly reduced formation of symmetrical dimethylargin
508	abolishes interaction with smn1; abolishes methylation by prmt9. abolishes formation of omega-n monomethylarginine and f
509	moderately diminished formation of omega-n monomethylarginine but greatly reduced formation of symmetrical dimethylargin
510	does not affect methylation by prmt9; when associated with a-506.
515	does not affect methylation by prmt9.
530	does not affect methylation by prmt9.
537	does not affect methylation by prmt9.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
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-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 575 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, MORF_HDAC1, MORF_UBE2N, MORF_RAD21, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, HSIAO_HOUSEKEEPING_GENES, MITSIADES_RESPONSE_TO_APLIDIN_DN, chr11q13, ATGTTAA_MIR302C, MAHAJAN_RESPONSE_TO_IL1A_DN, MARTINEZ_RB1_TARGETS_UP, MORF_SKP1A, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380), U2-type prespliceosome assembly (GO:1903241)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (10): 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), nuclear speck (GO:0016607), U2-type precatalytic spliceosome (GO:0071005), precatalytic spliceosome (GO:0071011), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
mRNA Splicing	2
mRNA 3’-end processing	1
Dengue Virus Infection	1
CHD chromatin remodelers	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
spliceosomal complex	4
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
spliceosomal complex assembly	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
Prp19 complex	1
U5 snRNP	1
catalytic complex	1

Protein interactions and networks

STRING

2755 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SF3B2	SF3B4	Q15427	999
SF3B2	SF3B3	Q15393	999
SF3B2	PHF5A	Q7RTV0	996
SF3B2	SF3B1	O75533	996
SF3B2	SF3B5	Q9BWJ5	996
SF3B2	SF3B6	Q9Y3B4	992
SF3B2	SF3A3	Q12874	977
SF3B2	SF3A2	Q15428	951
SF3B2	SF3A1	Q15459	920
SF3B2	RBM7	Q9Y580	916
SF3B2	SRSF3	P23152	833
SF3B2	EFTUD2	Q15029	778
SF3B2	SNRNP200	O75643	761
SF3B2	U2AF2	P26368	735
SF3B2	SNRPA1	P09661	730

IntAct

352 interactions, top by confidence:

A	B	Type	Score
SF3B2	SF3B4	psi-mi:“MI:0915”(physical association)	0.910
SF3B2	SF3B4	psi-mi:“MI:0914”(association)	0.910
SF3B4	SF3B2	psi-mi:“MI:0915”(physical association)	0.910
RBM7	SF3B2	psi-mi:“MI:0915”(physical association)	0.780
RBM7	SF3B2	psi-mi:“MI:0914”(association)	0.780
PRMT9	SF3B2	psi-mi:“MI:0914”(association)	0.750
PRMT9	SF3B2	psi-mi:“MI:0915”(physical association)	0.750
PRMT9	SF3B2	psi-mi:“MI:0213”(methylation reaction)	0.750
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:0914”(association)	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
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	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

BioGRID (799): SF3B2 (Two-hybrid), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS), SF3B2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: Q02554, Q13435, Q3UJB0, Q9UUI3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SF3B2	“form complex”	SF3b	binding
SF3B2	“form complex”	“U2 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 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	10	47.0×	1e-13
mRNA Splicing	31	25.2×	9e-34
mRNA Splicing - Minor Pathway	15	24.9×	1e-15
mRNA Polyadenylation	35	22.8×	3e-36
SARS-CoV-2 modulates host translation machinery	13	21.6×	1e-12
Processing of Capped Intron-Containing Pre-mRNA	35	21.3×	2e-35
Transport of Mature Transcript to Cytoplasm	7	19.7×	2e-06
RNA Polymerase II Transcription Termination	12	19.5×	4e-11

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	18	66.1×	1e-27
spliceosomal complex assembly	11	38.9×	4e-13
spliceosomal snRNP assembly	11	37.6×	5e-13
mRNA cis splicing, via spliceosome	6	35.0×	1e-06
RNA splicing, via transesterification reactions	9	33.0×	5e-10
mRNA splicing, via spliceosome	40	21.6×	2e-39
RNA splicing	30	15.6×	7e-25
regulation of alternative mRNA splicing, via spliceosome	8	11.5×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	133
Likely benign	18
Benign	13

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1342661	NM_006842.3(SF3B2):c.1780-2del	Pathogenic
1342662	NM_006842.3(SF3B2):c.1912C>T (p.Arg638Ter)	Pathogenic
1342663	NM_006842.3(SF3B2):c.1A>T (p.Met1Leu)	Pathogenic
3254890	NM_006842.3(SF3B2):c.664C>T (p.Arg222Ter)	Pathogenic
3383153	NM_006842.3(SF3B2):c.180+2T>C	Pathogenic
376005	NM_012433.4(SF3B1):c.1998G>C (p.Lys666Asn)	Likely pathogenic
376534	NM_012433.4(SF3B1):c.1874G>A (p.Arg625His)	Likely pathogenic
4082047	NM_006842.3(SF3B2):c.1107dup (p.Glu370Ter)	Likely pathogenic
4278404	NM_012433.4(SF3B1):c.1866G>C (p.Glu622Asp)	Likely pathogenic
4292971	NM_006842.3(SF3B2):c.2101del (p.Glu701fs)	Likely pathogenic

SpliceAI

2733 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66052516:GG:G	donor_gain	1.0000
11:66052516:GGGTG:G	donor_loss	1.0000
11:66052517:GG:G	donor_gain	1.0000
11:66052518:G:GA	donor_loss	1.0000
11:66052531:G:GT	donor_gain	1.0000
11:66052715:GCCAG:G	donor_gain	1.0000
11:66052720:G:GG	donor_gain	1.0000
11:66052720:GT:G	donor_loss	1.0000
11:66053022:T:A	acceptor_gain	1.0000
11:66053022:TGCA:T	acceptor_loss	1.0000
11:66053023:GCA:G	acceptor_loss	1.0000
11:66053024:CA:C	acceptor_loss	1.0000
11:66053025:A:AG	acceptor_gain	1.0000
11:66053025:AGACT:A	acceptor_gain	1.0000
11:66053026:G:GA	acceptor_gain	1.0000
11:66053026:GA:G	acceptor_gain	1.0000
11:66053026:GAC:G	acceptor_gain	1.0000
11:66053026:GACT:G	acceptor_gain	1.0000
11:66053026:GACTG:G	acceptor_gain	1.0000
11:66053102:CAGGT:C	donor_loss	1.0000
11:66053105:G:C	donor_loss	1.0000
11:66053105:G:GG	donor_gain	1.0000
11:66053106:T:A	donor_loss	1.0000
11:66055582:GCGG:G	donor_gain	1.0000
11:66056834:GTA:G	acceptor_loss	1.0000
11:66056837:GGC:G	acceptor_gain	1.0000
11:66056837:GGCA:G	acceptor_gain	1.0000
11:66056952:CGAGG:C	donor_loss	1.0000
11:66056953:GAGG:G	donor_loss	1.0000
11:66056954:AG:A	donor_loss	1.0000

AlphaMissense

5847 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66058106:T:C	L277P	1.000
11:66059040:T:C	F393L	1.000
11:66059041:T:C	F393S	1.000
11:66059042:T:A	F393L	1.000
11:66059042:T:G	F393L	1.000
11:66059557:C:A	R455S	1.000
11:66059561:G:C	R456P	1.000
11:66059569:C:A	R459S	1.000
11:66059570:G:C	R459P	1.000
11:66059576:C:T	T461I	1.000
11:66059579:T:A	V462E	1.000
11:66059581:G:C	A463P	1.000
11:66059582:C:A	A463D	1.000
11:66059587:C:T	L465F	1.000
11:66059588:T:A	L465H	1.000
11:66059588:T:C	L465P	1.000
11:66059588:T:G	L465R	1.000
11:66059590:A:G	K466E	1.000
11:66059592:G:C	K466N	1.000
11:66059592:G:T	K466N	1.000
11:66059594:A:C	Q467P	1.000
11:66059783:T:C	L468P	1.000
11:66059786:T:A	V469E	1.000
11:66059792:G:C	R471P	1.000
11:66059795:C:A	P472H	1.000
11:66059797:G:C	D473H	1.000
11:66059801:T:A	V474D	1.000
11:66059803:G:A	V475M	1.000
11:66059803:G:C	V475L	1.000
11:66059803:G:T	V475L	1.000

dbSNP variants (sampled 300 via entrez): RS1000004252 (11:66065633 C>T), RS1000119972 (11:66065308 C>T), RS1000122418 (11:66054829 C>T), RS1001111307 (11:66051798 C>T), RS1001132754 (11:66066017 C>G,T), RS1001189898 (11:66066277 C>T), RS1001238629 (11:66057704 G>A), RS1001441504 (11:66057511 TTAAAC>T), RS1002167154 (11:66052077 C>A), RS1002283364 (11:66051871 A>C,G), RS1002653426 (11:66066415 A>G,T), RS1003244467 (11:66054442 A>C,G), RS1003394196 (11:66053146 C>A,G,T), RS1003411408 (11:66060551 G>A,C), RS1003478701 (11:66067416 C>T)

Disease associations

OMIM: gene MIM:605591 | disease phenotypes: MIM:164210, MIM:614286, MIM:608232, MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant
craniofacial microsomia 1	Strong	Autosomal dominant

Mondo (6): craniofacial microsomia 1 (MONDO:0958175), myelodysplastic syndrome (MONDO:0018881), neurodevelopmental disorder (MONDO:0700092), chronic myeloid leukemia (MONDO:0011996), acute myeloid leukemia (MONDO:0018874), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (4): Goldenhar syndrome (Orphanet:374), Myelodysplastic syndrome (Orphanet:52688), Chronic myeloid leukemia (Orphanet:521), Acute myeloid leukemia (Orphanet:519)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000074	Ureteropelvic junction obstruction
HP:0000076	Vesicoureteral reflux
HP:0000086	Ectopic kidney
HP:0000104	Renal agenesis
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000238	Hydrocephalus
HP:0000272	Malar flattening
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000528	Anophthalmia
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000636	Upper eyelid coloboma
HP:0000646	Amblyopia
HP:0000891	Cervical ribs
HP:0001140	Limbal dermoid
HP:0001249	Intellectual disability
HP:0001274	Agenesis of corpus callosum
HP:0001629	Ventricular septal defect

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST002481_8	Acne (severe)	3.000000e-11
GCST002539_41	Schizophrenia	2.000000e-11
GCST004521_180	Autism spectrum disorder or schizophrenia	3.000000e-11
GCST004521_275	Autism spectrum disorder or schizophrenia	7.000000e-09
GCST006041_36	Major depressive disorder	2.000000e-06
GCST006803_21	Schizophrenia	4.000000e-13
GCST007201_301	Schizophrenia	1.000000e-11
GCST007201_34	Schizophrenia	2.000000e-10
GCST007294_7	Body fat distribution (trunk fat ratio)	8.000000e-12
GCST007294_75	Body fat distribution (trunk fat ratio)	1.000000e-07
GCST007295_158	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_48	Body fat distribution (leg fat ratio)	3.000000e-09
GCST007565_1	Morning person	8.000000e-21
GCST007565_75	Morning person	3.000000e-23
GCST008103_21	Bipolar disorder	2.000000e-08
GCST008595_62	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-09
GCST009391_728	Metabolite levels	1.000000e-06
GCST010698_25	Subcortical volume (min-P)	2.000000e-08
GCST010699_24	Brain morphology (min-P)	1.000000e-09
GCST010700_25	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_25	Cortical surface area (MOSTest)	2.000000e-37
GCST010702_65	Subcortical volume (MOSTest)	1.000000e-11
GCST010703_197	Brain morphology (MOSTest)	1.000000e-11
GCST012226_192	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009774	serine measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0007789	BMI-adjusted waist circumference

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): CHEMBL1229011 (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

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	Kd	6.909	nM	CHEMBL3752910
8.16	ED50	6.909	nM	CHEMBL3752910
7.10	IC50	80	nM	MOLIBRESIB
7.09	Kd	82	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 22 total; 2 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	2149386: Binding affinity to human SF3B2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0069	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	2178498: Inhibition of SF3B2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
cobaltous chloride	decreases expression	1
coumarin	decreases phosphorylation	1
hinokiflavone	increases sumoylation	1
yessotoxin	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Glyphosate	affects methylation	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases phosphorylation	1
Ribonucleotides	affects binding	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1
T-2 Toxin	increases expression	1
Thiram	increases expression	1
Valproic Acid	increases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226391	Binding	Binding affinity to SAP145 in human HeLa cells at 2 uM by LC-MS/MS analysis	Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. — Nat Chem Biol

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
NCT00005863	PHASE3	COMPLETED	Combination Chemotherapy With or Without Filgrastim and/or Tretinoin in Treating Patients With Acute Myeloid Leukemia