SF3A3

Summary

SF3A3 (splicing factor 3a subunit 3, HGNC:10767) is a protein-coding gene on chromosome 1p34.3, encoding Splicing factor 3A subunit 3 (Q12874). 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 99.9% of cancer cell lines).

This gene encodes subunit 3 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 3 interacts with subunit 1 through its amino-terminus while the zinc finger domain of subunit 3 plays a role in its binding to the 15S U2 snRNP. This gene has a pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10946 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_006802

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10767
Approved symbol	SF3A3
Name	splicing factor 3a subunit 3
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	SF3a60, SAP61, PRP9, PRPF9
Ensembl gene	ENSG00000183431
Ensembl biotype	protein_coding
OMIM	605596
Entrez	10946

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000373019, ENST00000460925, ENST00000461869, ENST00000462258, ENST00000470585, ENST00000487062, ENST00000488934, ENST00000489537, ENST00000896912, ENST00000896913, ENST00000896914, ENST00000896915, ENST00000896916, ENST00000931598, ENST00000931599, ENST00000931600, ENST00000931601, ENST00000931602, ENST00000931603, ENST00000931604, ENST00000931605, ENST00000963484, ENST00000963485, ENST00000963486

RefSeq mRNA: 2 — MANE Select: NM_006802 NM_001320830, NM_006802

CCDS: CCDS428

Canonical transcript exons

ENST00000373019 — 17 exons

Exon	Start	End
ENSE00001297977	37978720	37978827
ENSE00001305949	37960120	37960175
ENSE00001309816	37968044	37968134
ENSE00001323678	37969354	37969464
ENSE00001459316	37956975	37958263
ENSE00001809460	37989870	37990022
ENSE00003470568	37987784	37987836
ENSE00003478911	37984707	37984779
ENSE00003505647	37976884	37976953
ENSE00003517198	37979465	37979533
ENSE00003525478	37984169	37984260
ENSE00003572596	37980586	37980724
ENSE00003574509	37989548	37989595
ENSE00003581862	37981729	37981811
ENSE00003599837	37978988	37979055
ENSE00003649850	37969571	37969735
ENSE00003653365	37987573	37987678

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.7956 / max 1551.1857, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11819	46.9602	1816
11820	7.1584	1740
11821	0.6769	424

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.67	gold quality
calcaneal tendon	UBERON:0003701	96.14	gold quality
colonic epithelium	UBERON:0000397	95.86	gold quality
ganglionic eminence	UBERON:0004023	95.47	gold quality
tendon	UBERON:0000043	95.20	gold quality
ventricular zone	UBERON:0003053	95.12	gold quality
monocyte	CL:0000576	94.65	gold quality
leukocyte	CL:0000738	94.34	gold quality
mononuclear cell	CL:0000842	94.32	gold quality
rectum	UBERON:0001052	94.30	gold quality
muscle of leg	UBERON:0001383	93.90	gold quality
gastrocnemius	UBERON:0001388	93.79	gold quality
islet of Langerhans	UBERON:0000006	93.75	gold quality
stromal cell of endometrium	CL:0002255	93.72	gold quality
granulocyte	CL:0000094	93.69	gold quality
tendon of biceps brachii	UBERON:0008188	93.60	gold quality
cortical plate	UBERON:0005343	93.33	gold quality
body of uterus	UBERON:0009853	93.28	gold quality
mucosa of stomach	UBERON:0001199	93.21	gold quality
embryo	UBERON:0000922	93.19	gold quality
tibial artery	UBERON:0007610	93.15	gold quality
popliteal artery	UBERON:0002250	93.14	gold quality
right ovary	UBERON:0002118	93.07	gold quality
descending thoracic aorta	UBERON:0002345	93.03	gold quality
left uterine tube	UBERON:0001303	92.98	gold quality
right coronary artery	UBERON:0001625	92.86	gold quality
aorta	UBERON:0000947	92.77	gold quality
tibial nerve	UBERON:0001323	92.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.48	gold quality
lower esophagus	UBERON:0013473	92.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting SF3A3, 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-3163	100.00	77.23	8605
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-30C-1-3P	97.80	66.36	1499

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• SF3a60, 66, and 120, but not SF1, are essential for pre-mRNA splicing (PMID:15647371)
• SF3a3 functions as a co-repressor of Constitutive Androstane Receptor transcriptional activity, in addition to its canonical function. (PMID:18713018)
• The interaction between CSR1 and SF3A3 led to migration of SF3A3 from nucleus to cytoplasm. The cytoplasmic redistribution of SF3A3 significantly reduced the splicing efficiency of epidermal growth factor receptor and platelet-derived growth factor receptor. (PMID:27148859)
• Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer. (PMID:33662273)
• CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling. (PMID:35365208)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sf3a3	ENSDARG00000100114
mus_musculus	Sf3a3	ENSMUSG00000028902
rattus_norvegicus	Sf3a3	ENSRNOG00000007629
drosophila_melanogaster	noi	FBGN0014366
caenorhabditis_elegans		WBGENE00011758

Paralogs (1): SDE2 (ENSG00000143751)

Protein

Protein identifiers

Splicing factor 3A subunit 3 — Q12874 (reviewed: Q12874)

Alternative names: SF3a60, Spliceosome-associated protein 61

All UniProt accessions (1): Q12874

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, SF3A3 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). 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.

Subcellular location. Nucleus speckle. Nucleus.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the SF3A3 family.

RefSeq proteins (2): NP_001307759, NP_006793* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000690	Matrin/U1-C_Znf_C2H2	Domain
IPR021966	SF3a60_bindingd	Domain
IPR024598	SF3a60/Prp9_C	Domain
IPR025086	SDE2/SF3A3_SAP	Domain
IPR031774	SF3A3_dom	Domain
IPR051421	RNA_Proc_DNA_Dmg_Regulator	Family

Pfam: PF11931, PF12108, PF13297, PF16837

UniProt features (59 total): helix 23, strand 10, modified residue 9, turn 9, compositionally biased region 2, chain 1, zinc finger region 1, mutagenesis site 1, sequence conflict 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

46 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
7VPX	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	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
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
8R0B	ELECTRON MICROSCOPY	4.4
6FF7	ELECTRON MICROSCOPY	4.5
7ABH	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12874-F1	86.68	0.56

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 (9): 299, 365, 367, 369, 475, 1, 54, 121, 295

Mutagenesis-validated functional residues (1):

Position	Phenotype
174–180	loss of nuclear location.

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: 241 (showing top): MORF_DNMT1, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, PAL_PRMT5_TARGETS_UP, MODULE_388, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, chr1p34, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, GOBP_MRNA_SPLICE_SITE_RECOGNITION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (6): RNA splicing, via transesterification reactions (GO:0000375), mRNA 3’-splice site recognition (GO:0000389), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), U2-type prespliceosome assembly (GO:1903241), RNA splicing (GO:0008380)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): 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 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
binding	2
spliceosomal complex	2
RNA splicing	1
mRNA splice site recognition	1
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
transition metal ion binding	1
cation 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

3371 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SF3A3	SF3A1	Q15459	999
SF3A3	SF3A2	Q15428	999
SF3A3	SF3B2	Q13435	977
SF3A3	SF3B3	Q15393	969
SF3A3	SF3B4	Q15427	931
SF3A3	SFSWAP	Q12872	898
SF3A3	SNRPA1	P09661	853
SF3A3	SF3B1	O75533	829
SF3A3	EFTUD2	Q15029	810
SF3A3	SF3B5	Q9BWJ5	801
SF3A3	DDX46	Q7L014	797
SF3A3	PHF5A	Q7RTV0	785
SF3A3	SF3B6	Q9Y3B4	764
SF3A3	SNRNP200	O75643	750
SF3A3	U2AF1	Q01081	738

IntAct

208 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
SMNDC1	SF3B1	psi-mi:“MI:0914”(association)	0.790
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
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
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
ZNF212	SF3A3	psi-mi:“MI:0915”(physical association)	0.670
SF3A3	ZNF212	psi-mi:“MI:0915”(physical association)	0.670
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
NCBP2	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

BioGRID (462): SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Two-hybrid), SF3A3 (Two-hybrid), TRIM69 (Two-hybrid), SF3A3 (Two-hybrid), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS), SF3A3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P5, A1L1R0, A8E7C5, A8PJX4, A9UZS7, B3MG50, B3N9E4, B4GDK5, B4HR78, B4KSY3, B4P238, E7EXT2, E7F187, F7AEX0, O43076, O80452, O88379, P0CU29, P40486, P41229, P41230, P69735, P83093, P91133, Q05B18, Q09305, Q0E9G3, Q12874, Q14738, Q17N71, Q292G3, Q2PE14, Q38JA7, Q58CP9, Q7PTC5, Q7Q9F6, Q7Z3E5, Q80Y84, Q851S7, Q8R2R3

Diamond homologs: O46106, O59706, Q07G43, Q12874, Q5BJN8, Q5RET9, Q6IQ49, Q6NRI5, Q7T293, Q8K1J5, Q9D554, Q9FG01, O14113, P19736

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SF3A3	“form complex”	SF3a	binding
SF3A3	“form complex”	“U2 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 183 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	31.7×	7e-08
mRNA Splicing	31	24.3×	4e-33
mRNA Polyadenylation	37	23.2×	7e-39
mRNA Splicing - Minor Pathway	14	22.4×	7e-14
Processing of Capped Intron-Containing Pre-mRNA	35	20.5×	1e-34
mRNA Splicing - Major Pathway	46	17.9×	3e-43
CHD1 and CHD2 subfamily	23	17.9×	7e-21
Transport of Mature Transcript to Cytoplasm	6	16.3×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	17	62.4×	2e-25
spliceosomal complex assembly	10	35.4×	3e-11
spliceosomal snRNP assembly	8	27.4×	6e-08
negative regulation of mRNA splicing, via spliceosome	6	27.0×	9e-06
RNA splicing, via transesterification reactions	6	22.0×	3e-05
mRNA splicing, via spliceosome	37	19.9×	7e-35
RNA splicing	25	13.0×	2e-18
regulation of alternative mRNA splicing, via spliceosome	8	11.5×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1888 predictions. Top by Δscore:

Variant	Effect	Δscore
1:37968038:A:AC	donor_gain	1.0000
1:37968039:C:CC	donor_gain	1.0000
1:37968039:CTTA:C	donor_gain	1.0000
1:37968042:A:AC	donor_gain	1.0000
1:37968043:C:CT	donor_gain	1.0000
1:37968043:CAGG:C	donor_gain	1.0000
1:37968130:CATTC:C	acceptor_gain	1.0000
1:37968132:TTC:T	acceptor_gain	1.0000
1:37968133:TC:T	acceptor_gain	1.0000
1:37968134:CC:C	acceptor_gain	1.0000
1:37968135:C:CC	acceptor_gain	1.0000
1:37968135:C:CG	acceptor_loss	1.0000
1:37968136:T:A	acceptor_loss	1.0000
1:37969344:AATT:A	donor_gain	1.0000
1:37969347:T:TA	donor_gain	1.0000
1:37969352:A:AC	donor_gain	1.0000
1:37969353:C:CC	donor_gain	1.0000
1:37969353:CAG:C	donor_gain	1.0000
1:37969461:TAGG:T	acceptor_gain	1.0000
1:37969465:C:CC	acceptor_gain	1.0000
1:37969566:CTTA:C	donor_gain	1.0000
1:37969567:TTACT:T	donor_loss	1.0000
1:37969568:TA:T	donor_loss	1.0000
1:37969569:A:AC	donor_gain	1.0000
1:37969569:AC:A	donor_loss	1.0000
1:37969570:C:CG	donor_gain	1.0000
1:37969570:CT:C	donor_gain	1.0000
1:37969570:CTT:C	donor_gain	1.0000
1:37969570:CTTT:C	donor_gain	1.0000
1:37969570:CTTTG:C	donor_gain	1.0000

AlphaMissense

3314 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:37958193:A:G	L500P	1.000
1:37958199:T:G	Q498P	1.000
1:37958201:T:A	R497S	1.000
1:37958201:T:G	R497S	1.000
1:37958202:C:A	R497I	1.000
1:37958202:C:G	R497T	1.000
1:37958208:A:G	L495P	1.000
1:37958208:A:T	L495Q	1.000
1:37958212:C:G	D494H	1.000
1:37958235:A:T	V486D	1.000
1:37958241:C:A	G484V	1.000
1:37958241:C:T	G484E	1.000
1:37958242:C:A	G484W	1.000
1:37958242:C:G	G484R	1.000
1:37958242:C:T	G484R	1.000
1:37958249:G:C	D481E	1.000
1:37958249:G:T	D481E	1.000
1:37958250:T:A	D481V	1.000
1:37958250:T:G	D481A	1.000
1:37958251:C:G	D481H	1.000
1:37958252:T:A	E480D	1.000
1:37958252:T:G	E480D	1.000
1:37960135:C:A	W471C	1.000
1:37960135:C:G	W471C	1.000
1:37960137:A:G	W471R	1.000
1:37960137:A:T	W471R	1.000
1:37960163:A:G	L462P	1.000
1:37960173:A:G	W459R	1.000
1:37960173:A:T	W459R	1.000
1:37960175:A:G	L458S	1.000

dbSNP variants (sampled 300 via entrez): RS1000079417 (1:37991482 T>A,C), RS1000129607 (1:37985121 T>C), RS1000169830 (1:37962987 C>A), RS1000238447 (1:37966172 C>A,T), RS1000295215 (1:37960093 C>A), RS1000366997 (1:37961242 C>T), RS1000431854 (1:37959880 C>T), RS1000481002 (1:37980149 G>A,T), RS1000616099 (1:37961504 A>T), RS1000754505 (1:37959899 A>G), RS1000879361 (1:37986246 C>T), RS1000993622 (1:37985903 T>C), RS1001012294 (1:37979308 AT>A,ATT), RS1001245515 (1:37972836 C>T), RS1001294177 (1:37965714 A>G)

Disease associations

OMIM: gene MIM:605596 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004278_3	Pulse pressure	4.000000e-16
GCST005194_115	Coronary artery disease	1.000000e-09
GCST005195_64	Coronary artery disease	4.000000e-10
GCST005196_180	Coronary artery disease	7.000000e-10
GCST006288_601	Heel bone mineral density	8.000000e-10
GCST006979_872	Heel bone mineral density	4.000000e-29
GCST007267_171	Systolic blood pressure	2.000000e-08
GCST008163_379	Height	2.000000e-06
GCST010866_13	Coronary artery disease	9.000000e-14
GCST90000025_915	Appendicular lean mass	8.000000e-26

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465304 (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
8.01	Kd	9.697	nM	CHEMBL5653589
8.01	ED50	9.697	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 9 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	2149384: Binding affinity to human SF3A3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0097	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression, increases abundance	1
nivalenol	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
phenethyl isothiocyanate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
PP242	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338457	Binding	Binding affinity to Sf3a3 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — 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_D8V1	Ubigene HCT 116 SF3A3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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