SF3A1

Summary

SF3A1 (splicing factor 3a subunit 1, HGNC:10765) is a protein-coding gene on chromosome 22q12.2, encoding Splicing factor 3A subunit 1 (Q15459). 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 a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing.

Source: NCBI Gene 10291 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005877

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10765
Approved symbol	SF3A1
Name	splicing factor 3a subunit 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	SF3a120, SAP114, PRPF21, Prp21
Ensembl gene	ENSG00000099995
Ensembl biotype	protein_coding
OMIM	605595
Entrez	10291

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 retained_intron, 4 protein_coding, 2 nonsense_mediated_decay

ENST00000215793, ENST00000411423, ENST00000444440, ENST00000447376, ENST00000463818, ENST00000471037, ENST00000471342, ENST00000485618, ENST00000496189, ENST00000498259, ENST00000872796, ENST00000872797

RefSeq mRNA: 1 — MANE Select: NM_005877 NM_005877

CCDS: CCDS13875

Canonical transcript exons

ENST00000215793 — 16 exons

Exon	Start	End
ENSE00000652187	30335652	30335753
ENSE00000652188	30337026	30337180
ENSE00000652193	30340695	30340812
ENSE00000652194	30341692	30341885
ENSE00000652197	30344933	30345190
ENSE00000652198	30346312	30346519
ENSE00001332326	30337690	30337897
ENSE00001332335	30335467	30335538
ENSE00001332338	30340196	30340381
ENSE00001361929	30342200	30342350
ENSE00001701490	30331988	30334695
ENSE00001817075	30356730	30356894
ENSE00003472327	30342805	30342879
ENSE00003499675	30352951	30353072
ENSE00003519368	30339130	30339251
ENSE00003628671	30338789	30339034

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 142.9451 / max 1006.6605, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193623	140.5935	1828
193620	1.4059	950
193621	0.5234	293
193619	0.4222	200

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.76	gold quality
male germ cell	CL:0000015	98.23	gold quality
sural nerve	UBERON:0015488	97.06	gold quality
stromal cell of endometrium	CL:0002255	96.82	gold quality
ganglionic eminence	UBERON:0004023	96.66	gold quality
ventricular zone	UBERON:0003053	96.61	gold quality
colonic epithelium	UBERON:0000397	96.46	gold quality
bone marrow cell	CL:0002092	95.96	gold quality
cortical plate	UBERON:0005343	95.76	gold quality
left ovary	UBERON:0002119	95.51	gold quality
left testis	UBERON:0004533	95.51	gold quality
right testis	UBERON:0004534	95.47	gold quality
vermiform appendix	UBERON:0001154	95.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.34	gold quality
blood	UBERON:0000178	95.16	gold quality
right ovary	UBERON:0002118	95.05	gold quality
tonsil	UBERON:0002372	94.89	gold quality
lymph node	UBERON:0000029	94.85	gold quality
granulocyte	CL:0000094	94.82	gold quality
islet of Langerhans	UBERON:0000006	94.56	gold quality
body of uterus	UBERON:0009853	94.55	gold quality
caecum	UBERON:0001153	94.54	gold quality
embryo	UBERON:0000922	94.49	gold quality
leukocyte	CL:0000738	94.44	gold quality
nipple	UBERON:0002030	94.40	gold quality
right lung	UBERON:0002167	94.35	gold quality
testis	UBERON:0000473	94.34	gold quality
mononuclear cell	CL:0000842	94.24	gold quality
popliteal artery	UBERON:0002250	94.21	gold quality
tibial artery	UBERON:0007610	94.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

108 targeting SF3A1, 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-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 7)

• SF3a60, 66, and 120, but not SF1, are essential for pre-mRNA splicing (PMID:15647371)
• the SF3A mRNA splicing complex controls production of a negative regulator of TLR signaling that limits the extent of innate immune activation. (PMID:24204290)
• show that U1-SL4 interacts with the SF3A1 protein of the U2 snRNP (PMID:25403181)
• SF3A1 polymorphisms are not associated with Colorectal Cancer Risk. (PMID:26079486)
• Polymorphisms in SF3A1 gene is associated with pancreatic cancer. (PMID:26498691)
• data show that the UBL domain of SF3A1 can function as an RNA binding domain and that mutations in this region may interfere with U1-SL4 binding (PMID:31383795)
• Structural insights into recognition of SL4, the UUCG stem-loop, of human U1 snRNA by the ubiquitin-like domain, including the C-terminal tail in the SF3A1 subunit of U2 snRNP. (PMID:37094335)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sf3a1	ENSDARG00000041887
mus_musculus	Sf3a1	ENSMUSG00000002129
rattus_norvegicus	Sf3a1	ENSRNOG00000005218
drosophila_melanogaster	Sf3a1	FBGN0266917
caenorhabditis_elegans		WBGENE00004188

Protein

Protein identifiers

Splicing factor 3A subunit 1 — Q15459 (reviewed: Q15459)

Alternative names: SF3a120, Spliceosome-associated protein 114

All UniProt accessions (4): Q15459, F8WB66, F8WC79, H7C1L2

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, SF3A1 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome ‘E’ complex and the pre-catalytic spliceosome ‘A’ complex. Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome ‘B’ complexes.

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 SF3A subcomplex of the 17S U2 SnRNP complex which is composed of three subunits; SF3A3/SAP61, SF3A2/SAP62 and SF3A1/SAP114. SF3A associates with the splicing factor SF3B and a 12S RNA unit to form the mature 17S U2 small nuclear ribonucleoprotein complex (17S U2 snRNP). SF3A1 functions as a scaffold that interacts directly with both SF3A2 and SF3A3. Identified in the spliceosome ‘E’ complex, a precursor of the spliceosome ‘A’ complex. Identified in the spliceosome ‘A’ and ‘B’ complexes. Identified in the spliceosome ‘C’ complex. Interacts with P2RX6; resulting in a reduction of the splicing activity.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Ubiquitously expressed.

Domain organisation. SURP motif 2 mediates direct binding to SF3A3.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15459-1	1	yes
Q15459-2	2

RefSeq proteins (1): NP_005868* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000061	Surp	Domain
IPR000626	Ubiquitin-like_dom	Domain
IPR022030	SF3A1_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035563	SF3As1_ubi	Domain
IPR035967	SWAP/Surp_sf	Homologous_superfamily
IPR045146	SF3A1	Family

Pfam: PF00240, PF01805, PF12230

UniProt features (74 total): helix 18, strand 12, compositionally biased region 9, modified residue 9, region of interest 6, cross-link 6, mutagenesis site 4, repeat 2, turn 2, initiator methionine 1, chain 1, site 1, splice variant 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7P0V	X-RAY DIFFRACTION	1.56
8ID2	X-RAY DIFFRACTION	1.8
7EVO	ELECTRON MICROSCOPY	2.5
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
8HK1	ELECTRON MICROSCOPY	2.7
7VPX	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8Q7N	ELECTRON MICROSCOPY	3.1
8QOZ	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
6QX9	ELECTRON MICROSCOPY	3.28
8I0P	ELECTRON MICROSCOPY	3.4
9ZE0	ELECTRON MICROSCOPY	3.43
8QP8	ELECTRON MICROSCOPY	3.5
9ZEC	ELECTRON MICROSCOPY	3.61
8QPA	ELECTRON MICROSCOPY	3.7
8QPB	ELECTRON MICROSCOPY	3.7
6AHD	ELECTRON MICROSCOPY	3.8
9ZE3	ELECTRON MICROSCOPY	3.93
9ZED	ELECTRON MICROSCOPY	3.94
8QP9	ELECTRON MICROSCOPY	4.1
8QZS	ELECTRON MICROSCOPY	4.1
8I0S	ELECTRON MICROSCOPY	4.2
8QPK	ELECTRON MICROSCOPY	4.2
8R09	ELECTRON MICROSCOPY	4.3
8R0B	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15459-F1	67.76	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.

Catalytic / active sites (1): 169 (critical for binding to sf3a3)

Post-translational modifications (15): 55, 320, 329, 359, 413, 451, 456, 508, 759, 20, 131, 424, 499, 542, 686

Mutagenesis-validated functional residues (4):

Position	Phenotype
48	slurp 1 motif acquires binding to sf3a3; when associated with leu-55.
55	slurp 1 motif acquires binding to sf3a3; when associated with phe-48.
162	no effect on binding to sf3a3.
169	abolishes binding to sf3a3.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major 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: 197 (showing top): TSENG_IRS1_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MORF_HDAC1, MORF_UBE2N, GGAMTNNNNNTCCY_UNKNOWN, YY1_Q6, MORF_CCNI, REACTOME_MRNA_3_END_PROCESSING, GROSS_HYPOXIA_VIA_ELK3_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, GOBP_MRNA_SPLICE_SITE_RECOGNITION

GO Biological Process (7): mRNA 3’-splice site recognition (GO:0000389), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), mRNA cis splicing, via spliceosome (GO:0045292), U2-type prespliceosome assembly (GO:1903241), RNA processing (GO:0006396), RNA splicing (GO:0008380)

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

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U2-type spliceosomal complex (GO:0005684), U2 snRNP (GO:0005686), nuclear speck (GO:0016607), U2-type prespliceosome (GO:0071004), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
mRNA Splicing	1
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
RNA processing	2
spliceosomal complex	2
U2-type spliceosomal complex	2
U1 snRNP	2
U2 snRNP	2
mRNA splice site recognition	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
mRNA splicing, via spliceosome	1
spliceosomal complex assembly	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	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
prespliceosome	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

3057 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SF3A1	SF3A3	Q12874	999
SF3A1	SF3A2	Q15428	999
SF3A1	SF3B2	Q13435	920
SF3A1	SF3B3	Q15393	877
SF3A1	U2AF1	Q01081	848
SF3A1	SF3B1	O75533	826
SF3A1	U2AF2	P26368	801
SF3A1	DDX46	Q7L014	788
SF3A1	SNRPA1	P09661	783
SF3A1	PRPF40B	Q6NWY9	783
SF3A1	SF3B4	Q15427	782
SF3A1	PHF5A	Q7RTV0	780
SF3A1	SF3B5	Q9BWJ5	778
SF3A1	SF3B6	Q9Y3B4	751
SF3A1	SNRNP200	O75643	723

IntAct

246 interactions, top by confidence:

A	B	Type	Score
SF1	U2AF2	psi-mi:“MI:0914”(association)	0.950
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SF3A3	SF3A1	psi-mi:“MI:0407”(direct interaction)	0.900
SF3A3	SF3A1	psi-mi:“MI:0915”(physical association)	0.900
SF3A2	SF3A1	psi-mi:“MI:0915”(physical association)	0.800
SMNDC1	SF3B1	psi-mi:“MI:0914”(association)	0.790
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
RBM17	U2SURP	psi-mi:“MI:0914”(association)	0.740
CCDC97	SF3B1	psi-mi:“MI:0914”(association)	0.730
PHF5A	SF3B1	psi-mi:“MI:0914”(association)	0.730
SF3A1	SF1	psi-mi:“MI:0407”(direct interaction)	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
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	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
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640

BioGRID (735): SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-RNA), SF3A1 (Affinity Capture-RNA), SF3A1 (Affinity Capture-RNA), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A2J9B3, A0A0K0QSV4, A0A9P4XWM4, A1CT57, A1DMG9, A7E8B6, A8JPF9, A8NYG2, A9LNK9, E5AD52, E7F1H9, G4MRQ6, G4NF05, M2SQ20, N1PJ97, O42632, P0C5H8, P0DPB0, P38093, P59326, P87253, Q05534, Q0U086, Q15459, Q1K6U0, Q2UNX4, Q2UPS5, Q4R1B9, Q4WN42, Q4WVG0, Q4WXX4, Q4X228, Q5B3I8, Q5RFL8, Q6DDU9, Q6L612, Q7RZQ3, Q7Z739, Q8BYK6, Q8K4Z5

Diamond homologs: A2VDN6, B9DHA6, G1SK22, O13900, O14399, O15042, P05759, P0C016, P0C030, P0C031, P0C032, P0C073, P0C8R3, P0CG71, P0CG73, P0CG81, P0CG82, P0CG83, P0CG84, P0CG85, P0CG86, P0CG87, P0CH04, P0CH05, P0CH10, P0CH11, P0CH27, P0CH32, P0CH33, P0CH34, P0CH35, P0DJ25, P12297, P14795, P14799, P15357, P19848, P23324, P23398, P27923

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SF3A1	“form complex”	SF3a	binding
SF3A1	“form complex”	“U2 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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	7	27.9×	2e-07
mRNA Splicing - Minor Pathway	16	22.5×	4e-16
mRNA Splicing	29	20.0×	5e-28
mRNA Polyadenylation	34	18.8×	6e-32
Processing of Capped Intron-Containing Pre-mRNA	31	16.0×	7e-27
mRNA Splicing - Major Pathway	46	15.8×	2e-40
CHD1 and CHD2 subfamily	23	15.7×	2e-19
RNA Polymerase II Transcription Termination	10	13.8×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	17	57.7×	1e-24
spliceosomal complex assembly	10	32.7×	6e-11
spliceosomal snRNP assembly	9	28.4×	4e-09
regulation of mRNA splicing, via spliceosome	5	24.1×	2e-04
RNA splicing, via transesterification reactions	7	23.7×	2e-06
mRNA splicing, via spliceosome	40	19.9×	6e-38
RNA splicing	24	11.5×	3e-16
mRNA processing	18	7.7×	4e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2671887	NM_005877.6(SF3A1):c.1641del (p.Ser548fs)	Pathogenic

SpliceAI

1952 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30334692:TACC:T	acceptor_gain	1.0000
22:30334693:ACC:A	acceptor_gain	1.0000
22:30334694:CC:C	acceptor_gain	1.0000
22:30334694:CCC:C	acceptor_gain	1.0000
22:30334695:CC:C	acceptor_gain	1.0000
22:30334696:C:A	acceptor_loss	1.0000
22:30334696:C:CC	acceptor_gain	1.0000
22:30334696:C:T	acceptor_gain	1.0000
22:30334697:T:A	acceptor_loss	1.0000
22:30335463:TCA:T	donor_loss	1.0000
22:30335464:CAC:C	donor_loss	1.0000
22:30335465:A:AC	donor_gain	1.0000
22:30335465:ACC:A	donor_loss	1.0000
22:30335466:C:CC	donor_gain	1.0000
22:30335466:C:T	donor_loss	1.0000
22:30335466:CCT:C	donor_gain	1.0000
22:30335539:C:CG	acceptor_loss	1.0000
22:30335540:T:A	acceptor_loss	1.0000
22:30335648:ATACC:A	donor_loss	1.0000
22:30335650:A:T	donor_loss	1.0000
22:30335651:C:CA	donor_loss	1.0000
22:30335752:CC:C	acceptor_gain	1.0000
22:30335753:CC:C	acceptor_gain	1.0000
22:30335754:C:CC	acceptor_gain	1.0000
22:30337021:CATA:C	donor_gain	1.0000
22:30337024:A:AC	donor_gain	1.0000
22:30337024:AC:A	donor_gain	1.0000
22:30337024:ACC:A	donor_loss	1.0000
22:30337025:C:CA	donor_gain	1.0000
22:30337025:CC:C	donor_gain	1.0000

AlphaMissense

5226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30334607:C:T	G790E	1.000
22:30334610:C:T	G789D	1.000
22:30334611:C:G	G789R	1.000
22:30334612:T:A	R788S	1.000
22:30334612:T:G	R788S	1.000
22:30334613:C:A	R788I	1.000
22:30334613:C:G	R788T	1.000
22:30334618:C:A	K786N	1.000
22:30334618:C:G	K786N	1.000
22:30334620:T:C	K786E	1.000
22:30334628:A:G	L783P	1.000
22:30334664:G:T	A771D	1.000
22:30334679:T:A	D766V	1.000
22:30334679:T:G	D766A	1.000
22:30334680:C:G	D766H	1.000
22:30334681:T:A	K765N	1.000
22:30334681:T:G	K765N	1.000
22:30334682:T:A	K765I	1.000
22:30334683:T:C	K765E	1.000
22:30334687:G:C	F763L	1.000
22:30334687:G:T	F763L	1.000
22:30334689:A:G	F763L	1.000
22:30335477:A:C	L757R	1.000
22:30335477:A:G	L757P	1.000
22:30335477:A:T	L757Q	1.000
22:30335479:C:A	K756N	1.000
22:30335479:C:G	K756N	1.000
22:30335481:T:C	K756E	1.000
22:30335482:C:A	Q755H	1.000
22:30335482:C:G	Q755H	1.000

dbSNP variants (sampled 300 via entrez): RS1000043391 (22:30345911 G>A), RS1000053334 (22:30346149 G>A,C), RS1000137910 (22:30346214 T>C), RS1000177740 (22:30339837 G>C), RS1000224841 (22:30332834 G>A,C), RS1000360049 (22:30333192 G>C), RS1000361607 (22:30333674 A>G), RS1000613153 (22:30339529 G>A), RS1000637672 (22:30339796 G>A,T), RS1000937942 (22:30356181 C>T), RS1000992619 (22:30350808 G>T), RS1001048914 (22:30344548 T>C), RS1001377847 (22:30358647 C>T), RS1001411936 (22:30358411 C>T), RS1001435280 (22:30350965 G>A,C)

Disease associations

OMIM: gene MIM:605595 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): diffuse large B-cell lymphoma (MONDO:0018905)

Orphanet (1): Diffuse large B-cell lymphoma (Orphanet:544)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005851_15	Delirium	1.000000e-06
GCST008794_13	Urinary albumin-to-creatinine ratio	2.000000e-08
GCST90002382_502	Eosinophil percentage of white cells	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725108 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.57	Kd	26.84	nM	CHEMBL5653589
7.57	ED50	26.84	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149382: Binding affinity to human SF3A1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0268	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
sodium arsenite	increases abundance, increases expression	3
Cyclosporine	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
butyraldehyde	decreases expression	1
coumarin	increases phosphorylation	1
yessotoxin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	increases secretion, affects cotreatment	1
abrine	increases expression	1
bromovanin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
10-(octyloxy)decyl-2-(trimethylammonium)ethyl phosphate	decreases expression	1
PP242	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652424	Binding	Binding affinity to human SF3A1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00466258	PHASE4	COMPLETED	LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)
NCT01949818	PHASE4	UNKNOWN	Treatment of Diffuse Large B Cell Lymphoma
NCT02752815	PHASE4	UNKNOWN	Reduced Chemotherapy in Low Risk DLBCL
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03513601	PHASE4	UNKNOWN	Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma
NCT03579082	PHASE4	UNKNOWN	A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma
NCT05108805	PHASE4	COMPLETED	Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting
NCT05518383	PHASE4	RECRUITING	B-cell Mature Non-Hodgkin’s Lymphoma Treatment Protocol in Children and Adolescents 2021
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
NCT00355199	PHASE3	COMPLETED	Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.
NCT00400478	PHASE3	COMPLETED	A Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment Versus Observation in Patients With Aggressive B-cell Lymphoma: NHL-13
NCT00499018	PHASE3	UNKNOWN	Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
NCT00790036	PHASE3	COMPLETED	Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy
NCT00846157	PHASE3	UNKNOWN	Biocell Natural Killer Mixture in Diffuse Large B Cell Lymphoma (DLBCL) Patients
NCT01122472	PHASE3	COMPLETED	Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
NCT01148446	PHASE3	COMPLETED	R-CHOP Versus R-mini-CEOP in Elderly Patients(>65)With DLBCL
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01285765	PHASE3	COMPLETED	Evaluate a Treatment Adapted to the PET Response Compared to a Standard Treatment, for Low Risk DLBCL CD 20+ Patients
NCT01287741	PHASE3	TERMINATED	A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)
NCT01321541	PHASE3	COMPLETED	Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant
NCT01459887	PHASE3	COMPLETED	Study of Recombinant Human-Mouse Chimeric Anti-CD20 Monoclonal Antibody to Treat Non-hodgkin’s Lymphoma
NCT01510184	PHASE3	TERMINATED	Study of Zevalin Versus Observation in Participants at Least 60 Years Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in Positron Emission Tomography (PET)-Negative Complete Remission After Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) or R-CHOP-like Therapy
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT01852435	PHASE3	UNKNOWN	R-CEOP-90/R-CEOP-70 Versus R-CHOP-50 in the Treatment of Diffuse Large B-cell Lymphoma and Follicular Lymphoma Grade 3B
NCT02054559	PHASE3	WITHDRAWN	R-CHOP Alone vs. R-CHOP Plus Radiotherapy for Localized CD20+ DLBCL
NCT02128061	PHASE3	COMPLETED	Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
NCT02268045	PHASE3	COMPLETED	Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin’s Lymphoma
NCT02366663	PHASE3	TERMINATED	BEAM vs. 90-Yttrium Ibritumomab Tiuxetan (Zevalin®)/BEAM With ASCT for Relapsed DLBCL
NCT02449265	PHASE3	UNKNOWN	Efficacy of Consolidative Involved-site Radiotherapy for Patients With Limited-stage Diffuse Large B-cell Lymphoma
NCT02449278	PHASE3	UNKNOWN	The Palliative Benefit of Involved-site Radiotherapy for Patients With Advanced-stage Diffuse Large B-cell Lymphoma
NCT02531841	PHASE3	UNKNOWN	High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma
NCT02617485	PHASE3	COMPLETED	MabionCD20 Compared to MabThera in Lymphoma Patients
NCT02767674	PHASE3	UNKNOWN	Trial of R-GemOx Versus R-miniCHOP Regimen in First-line Treatment of Elderly Diffuse Large B Cell Lymphoma
NCT02772822	PHASE3	UNKNOWN	A Study Comparing the Efficiency and Safety of S-CHOP(Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone) Versus R-CHOP in Untreated CD20(Cluster of Differentiation Antigen 20)-Positive DLBCL Patients
NCT02777736	PHASE3	UNKNOWN	CNS Prophylaxis in Diffuse Large B-cell Lymphoma
NCT02842931	PHASE3	UNKNOWN	R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis
NCT02951156	PHASE3	TERMINATED	Avelumab In Combination Regimens That Include An Immune Agonist, Epigenetic Modulator, CD20 Antagonist and/or Conventional Chemotherapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)
NCT03123718	PHASE3	UNKNOWN	High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for Central Nervous System Prophylaxis in DLBCL
NCT03151044	PHASE3	UNKNOWN	R±CEOP90 Versus R±CEOP75 in Newly Diagnosed Young Patients With Medium/High-risk DLBCL
NCT03213977	PHASE3	UNKNOWN	R-DA-EDOCH Versus R-CEOP90, With/Without Upfront Auto-HSCT in Young Patients With High-risk DLBCL