SFSWAP

Summary

SFSWAP (splicing factor SWAP, HGNC:10790) is a protein-coding gene on chromosome 12q24.33, encoding Splicing factor, suppressor of white-apricot homolog (Q12872). Plays a role as an alternative splicing regulator. It is a selective cancer dependency (DepMap: 85.7% of cell lines).

This gene encodes a human homolog of Drosophila splicing regulatory protein. This gene autoregulates its expression by control of splicing of its first two introns. In addition, it also regulates the splicing of fibronectin and CD45 genes. Two transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 6433 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 153 total
• Cancer dependency (DepMap): dependent in 85.7% of screened cell lines
• MANE Select transcript: NM_004592

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10790
Approved symbol	SFSWAP
Name	splicing factor SWAP
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	SWAP
Ensembl gene	ENSG00000061936
Ensembl biotype	protein_coding
OMIM	601945
Entrez	6433

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261674, ENST00000535202, ENST00000535236, ENST00000535399, ENST00000537164, ENST00000537582, ENST00000538548, ENST00000539506, ENST00000540469, ENST00000541286, ENST00000542813, ENST00000874197, ENST00000938425, ENST00000938426

RefSeq mRNA: 2 — MANE Select: NM_004592 NM_001261411, NM_004592

CCDS: CCDS58290, CCDS9273

Canonical transcript exons

ENST00000261674 — 18 exons

Exon	Start	End
ENSE00000757545	131714071	131714240
ENSE00001192361	131711090	131711447
ENSE00003478178	131755386	131755479
ENSE00003478347	131728293	131728428
ENSE00003480331	131719454	131719539
ENSE00003488332	131754368	131754499
ENSE00003544771	131766118	131766308
ENSE00003545593	131799423	131799738
ENSE00003547248	131756473	131756644
ENSE00003547411	131725405	131725630
ENSE00003579522	131753123	131753363
ENSE00003591589	131726940	131727052
ENSE00003596023	131797178	131797360
ENSE00003602742	131764456	131764686
ENSE00003632685	131714822	131714953
ENSE00003671685	131786463	131786588
ENSE00003686552	131778065	131778330
ENSE00003690728	131799037	131799109

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0584 / max 330.1331, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128757	27.9681	1819
128760	0.0904	35

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	97.30	gold quality
tendon of biceps brachii	UBERON:0008188	96.19	gold quality
olfactory bulb	UBERON:0002264	95.76	gold quality
medial globus pallidus	UBERON:0002477	94.64	gold quality
globus pallidus	UBERON:0001875	94.16	gold quality
lateral globus pallidus	UBERON:0002476	94.06	gold quality
tibial nerve	UBERON:0001323	93.62	gold quality
type B pancreatic cell	CL:0000169	93.55	silver quality
right hemisphere of cerebellum	UBERON:0014890	93.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.39	gold quality
cerebellar hemisphere	UBERON:0002245	93.11	gold quality
cardia of stomach	UBERON:0001162	93.01	gold quality
cerebellar cortex	UBERON:0002129	92.95	gold quality
left ovary	UBERON:0002119	92.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.61	gold quality
metanephros cortex	UBERON:0010533	92.59	gold quality
skin of leg	UBERON:0001511	92.51	gold quality
right ovary	UBERON:0002118	92.39	gold quality
skin of abdomen	UBERON:0001416	92.20	gold quality
mucosa of stomach	UBERON:0001199	92.08	gold quality
granulocyte	CL:0000094	92.06	gold quality
cerebellum	UBERON:0002037	92.00	gold quality
spinal cord	UBERON:0002240	91.91	gold quality
body of uterus	UBERON:0009853	91.84	gold quality
secondary oocyte	CL:0000655	91.83	gold quality
pylorus	UBERON:0001166	91.83	gold quality
endocervix	UBERON:0000458	91.76	gold quality
nipple	UBERON:0002030	91.75	gold quality
lower esophagus mucosa	UBERON:0035834	91.61	gold quality
tendon	UBERON:0000043	91.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.97
E-GEOD-124858	no	66.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting SFSWAP, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-552-3P	96.68	64.12	1026

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 85.7% of screened cell lines.

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sfswap	ENSDARG00000005980
mus_musculus	Sfswap	ENSMUSG00000029439
rattus_norvegicus	Sfswap	ENSRNOG00000000931
drosophila_melanogaster	su(w[a])	FBGN0003638

Paralogs (1): CLASRP (ENSG00000104859)

Protein

Protein identifiers

Splicing factor, suppressor of white-apricot homolog — Q12872 (reviewed: Q12872)

Alternative names: Splicing factor, arginine/serine-rich 8, Suppressor of white apricot protein homolog

All UniProt accessions (3): Q12872, F5H1A5, H0YFR9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as an alternative splicing regulator. Regulate its own expression at the level of RNA processing. Also regulates the splicing of fibronectin and CD45 genes. May act, at least in part, by interaction with other R/S-containing splicing factors. Represses the splicing of MAPT/Tau exon 10.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12872-1	1	yes
Q12872-2	2

RefSeq proteins (2): NP_001248340, NP_004583* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000061	Surp	Domain
IPR019147	SWAP_N_domain	Domain
IPR035967	SWAP/Surp_sf	Homologous_superfamily
IPR040397	SWAP	Family

Pfam: PF01805, PF09750

UniProt features (58 total): compositionally biased region 18, modified residue 8, helix 8, region of interest 7, sequence variant 7, strand 3, repeat 2, sequence conflict 2, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2E5Z	SOLUTION NMR
2E60	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12872-F1	61.71	0.15

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 (8): 283, 315, 604, 642, 832, 834, 905, 909

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 191 (showing top): GGGACCA_MIR133A_MIR133B, ACTACCT_MIR196A_MIR196B, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, AAGCCAT_MIR135A_MIR135B, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GGGTGGRR_PAX4_03, MORF_RAF1, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_FANCG, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, AGGAGTG_MIR483, MORF_RAP1A, GOBP_MRNA_SPLICE_SITE_RECOGNITION

GO Biological Process (6): alternative mRNA splicing, via spliceosome (GO:0000380), mRNA 5’-splice site recognition (GO:0000395), negative regulation of mRNA splicing, via spliceosome (GO:0048025), RNA processing (GO:0006396), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA splicing, via spliceosome	2
RNA processing	2
mRNA splice site recognition	1
mRNA cis splicing, via spliceosome	1
negative regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
negative regulation of mRNA processing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFSWAP	SF3A3	Q12874	898
SFSWAP	SF3A2	Q15428	871
SFSWAP	SRRM4	A7MD48	542
SFSWAP	PRP4K	Q13523	502
SFSWAP	SUGP2	Q8IX01	479
SFSWAP	BORCS8	Q96FH0	472
SFSWAP	SRSF11	Q05519	461
SFSWAP	SREK1	Q8WXA9	448
SFSWAP	SF3A1	Q15459	441
SFSWAP	PTPRC	P08575	441
SFSWAP	SRSF5	Q13243	432
SFSWAP	SRRM1	Q8IYB3	430
SFSWAP	SRSF7	Q16629	422
SFSWAP	SRSF12	Q8WXF0	389
SFSWAP	ZNF705A	Q6ZN79	380

IntAct

69 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
RBM17	U2SURP	psi-mi:“MI:0914”(association)	0.740
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
CFAP20	SFSWAP	psi-mi:“MI:0914”(association)	0.620
SFSWAP	CFAP20	psi-mi:“MI:0915”(physical association)	0.620
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
CAPN13	SFSWAP	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
SFSWAP	SF1	psi-mi:“MI:0407”(direct interaction)	0.440
Nfya	NFYB	psi-mi:“MI:0914”(association)	0.350
NEIL3	SF3B2	psi-mi:“MI:0914”(association)	0.350
Cdkn2aip	SF1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
JMJD6	U2SURP	psi-mi:“MI:0914”(association)	0.350
RBM17	U2SURP	psi-mi:“MI:0914”(association)	0.350
CAPN13	EIF4E2	psi-mi:“MI:0914”(association)	0.350
CFAP20	PRPF40A	psi-mi:“MI:0914”(association)	0.350
TSEN2	XPC	psi-mi:“MI:0914”(association)	0.350
SRPK2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (122): SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Proximity Label-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS), SFSWAP (Affinity Capture-MS)

ESM2 similar proteins: A0JM64, A4IHD9, B5DF93, D3ZTQ1, E7F1H9, O70305, P70501, Q12872, Q13625, Q2NLB0, Q2T9I5, Q32SG5, Q3TC46, Q3TCX3, Q3USH5, Q498K9, Q566L7, Q5R413, Q5R8Q4, Q5SFM8, Q5T8P6, Q5ZL54, Q62415, Q66IJ0, Q68FI1, Q6DDU9, Q6GP15, Q6NXI6, Q6NZ18, Q6NZN0, Q6PEH8, Q7Z7F0, Q86TB9, Q8BG81, Q8CG79, Q8CGC4, Q8IZD4, Q8K2F8, Q8ND56, Q8R205

Diamond homologs: A0JNI5, D3ZTQ1, P12297, Q12872, Q3USH5, Q5HZB6, Q8CFC7, Q8N2M8, Q10580, A2VDN6, O13900, Q15459, Q8IWX8, Q8K4Z5, Q8RXF1, Q94C11

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
mRNA Splicing	9	19.0×	6e-08
mRNA 3’-end processing	5	18.9×	3e-04
mRNA Polyadenylation	10	16.9×	4e-08
Processing of Capped Intron-Containing Pre-mRNA	10	15.8×	5e-08
Transport of Mature mRNA derived from an Intron-Containing Transcript	5	14.6×	7e-04
mRNA Splicing - Major Pathway	12	12.6×	3e-08
CHD1 and CHD2 subfamily	6	12.6×	3e-04
Metabolism of RNA	12	9.6×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	11	14.1×	1e-07
mRNA splicing, via spliceosome	9	11.9×	1e-05
mRNA processing	9	10.3×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3333 predictions. Top by Δscore:

Variant	Effect	Δscore
12:131711444:ACAGG:A	donor_loss	1.0000
12:131711445:CAGGT:C	donor_loss	1.0000
12:131711446:AGGT:A	donor_loss	1.0000
12:131711448:G:GA	donor_loss	1.0000
12:131713649:GA:G	donor_gain	1.0000
12:131714068:CAGA:C	acceptor_loss	1.0000
12:131714069:A:AG	acceptor_gain	1.0000
12:131714070:G:GG	acceptor_gain	1.0000
12:131714070:GAT:G	acceptor_gain	1.0000
12:131714801:A:G	acceptor_gain	1.0000
12:131714809:A:AG	acceptor_gain	1.0000
12:131714810:T:G	acceptor_gain	1.0000
12:131714815:A:AG	acceptor_gain	1.0000
12:131714816:T:G	acceptor_gain	1.0000
12:131714817:TCAAG:T	acceptor_loss	1.0000
12:131714818:CAA:C	acceptor_loss	1.0000
12:131714819:A:AG	acceptor_gain	1.0000
12:131714819:AAGAG:A	acceptor_gain	1.0000
12:131714820:A:C	acceptor_loss	1.0000
12:131714820:A:G	acceptor_gain	1.0000
12:131714820:AGAG:A	acceptor_gain	1.0000
12:131714821:G:A	acceptor_loss	1.0000
12:131714821:G:GA	acceptor_gain	1.0000
12:131714821:GA:G	acceptor_gain	1.0000
12:131714821:GAGG:G	acceptor_gain	1.0000
12:131714821:GAGGA:G	acceptor_gain	1.0000
12:131714949:GAGAG:G	donor_gain	1.0000
12:131714951:GAG:G	donor_gain	1.0000
12:131714952:AGGTG:A	donor_loss	1.0000
12:131714954:G:GG	donor_gain	1.0000

AlphaMissense

6197 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:131711344:G:C	G39R	1.000
12:131711345:G:A	G39D	1.000
12:131725406:C:A	P203Q	1.000
12:131725406:C:G	P203R	1.000
12:131725433:T:A	I212N	1.000
12:131725439:G:C	R214P	1.000
12:131725444:G:C	A216P	1.000
12:131725445:C:A	A216D	1.000
12:131725450:T:C	F218L	1.000
12:131725451:T:C	F218S	1.000
12:131725452:C:A	F218L	1.000
12:131725452:C:G	F218L	1.000
12:131725481:T:A	I228N	1.000
12:131725481:T:C	I228T	1.000
12:131725481:T:G	I228S	1.000
12:131725487:T:C	L230P	1.000
12:131725516:T:C	F240L	1.000
12:131725517:T:C	F240S	1.000
12:131725517:T:G	F240C	1.000
12:131725518:T:A	F240L	1.000
12:131725518:T:G	F240L	1.000
12:131725522:T:C	F242L	1.000
12:131725523:T:C	F242S	1.000
12:131725523:T:G	F242C	1.000
12:131725524:T:A	F242L	1.000
12:131725524:T:G	F242L	1.000
12:131725526:T:C	L243P	1.000
12:131725544:T:C	L249P	1.000
12:131725552:T:G	Y252D	1.000
12:131725555:T:G	Y253D	1.000

dbSNP variants (sampled 300 via entrez): RS1000013530 (12:131795017 G>A), RS1000017790 (12:131725749 C>G), RS1000018015 (12:131759521 C>A,T), RS1000031607 (12:131754300 C>T), RS1000032574 (12:131762244 CAAAA>C,CAAA,CAAAAA), RS1000043878 (12:131746996 C>A,G,T), RS1000063880 (12:131716972 T>A), RS1000080367 (12:131731629 C>A), RS1000083283 (12:131751875 G>C,T), RS1000094235 (12:131767917 T>G), RS1000111038 (12:131712542 T>G), RS1000118086 (12:131710456 G>A,C), RS1000172305 (12:131710730 G>C), RS1000173356 (12:131785932 C>T), RS1000186007 (12:131789764 T>C)

Disease associations

OMIM: gene MIM:601945 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_3	Body mass index	6.000000e-09
GCST007600_89	Alzheimer’s disease	3.000000e-06
GCST009959_7	Retinal detachment or retinal break	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010698	retinal break

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	affects methylation	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Phenobarbital	affects expression	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1
Thiram	increases expression	1
Vitamin E	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Serpentine	decreases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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