SF1

Summary

SF1 (splicing factor 1, HGNC:12950) is a protein-coding gene on chromosome 11q13.1, encoding Splicing factor 1 (Q15637). Necessary for the ATP-dependent first step of spliceosome assembly.

This gene encodes a nuclear pre-mRNA splicing factor. The encoded protein specifically recognizes the intron branch point sequence at the 3’ splice site, together with the large subunit of U2 auxiliary factor (U2AF), and is required for the early stages of spliceosome assembly. It also plays a role in nuclear pre-mRNA retention and transcriptional repression. The encoded protein contains an N-terminal U2AF ligand motif, a central hnRNP K homology motif and quaking 2 region which bind a key branch-site adenosine within the branch point sequence, a zinc knuckles domain, and a C-terminal proline-rich domain. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7536 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 122 total — 2 likely-pathogenic
• Druggable target: yes
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_004630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12950
Approved symbol	SF1
Name	splicing factor 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	ZFM1, ZCCHC25, BBP
Ensembl gene	ENSG00000168066
Ensembl biotype	protein_coding
OMIM	601516
Entrez	7536

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 15 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000227503, ENST00000334944, ENST00000377387, ENST00000377390, ENST00000377394, ENST00000413725, ENST00000413951, ENST00000432725, ENST00000433274, ENST00000443908, ENST00000448404, ENST00000463343, ENST00000472725, ENST00000477596, ENST00000482693, ENST00000486867, ENST00000486960, ENST00000489544, ENST00000496969, ENST00000633899, ENST00000681407, ENST00000706684, ENST00000706685, ENST00000706686, ENST00000890453, ENST00000931519

RefSeq mRNA: 12 — MANE Select: NM_004630 NM_001178030, NM_001178031, NM_001346363, NM_001346364, NM_001346409, NM_001346410, NM_001378956, NM_001378957, NM_004630, NM_201995, NM_201997, NM_201998

CCDS: CCDS31599, CCDS44642, CCDS53660, CCDS53661, CCDS8080, CCDS8081, CCDS91502

Canonical transcript exons

ENST00000377390 — 13 exons

Exon	Start	End
ENSE00000863666	64767571	64767844
ENSE00001473768	64764606	64766155
ENSE00001875721	64778362	64778542
ENSE00003503698	64768106	64768286
ENSE00003527811	64776498	64776626
ENSE00003547307	64773430	64773505
ENSE00003565362	64769426	64769609
ENSE00003574050	64766900	64767079
ENSE00003589194	64770256	64770408
ENSE00003591764	64769223	64769338
ENSE00003605470	64769964	64770053
ENSE00003687094	64767192	64767251
ENSE00003692663	64769022	64769129

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 139.5460 / max 2781.5895, expressed in 1828 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120457	83.5189	1824
120458	45.5606	1819
120456	3.9909	1593
120459	2.8811	1436
120455	1.6674	926
120447	1.0620	670
120454	0.3839	133
120453	0.2110	83
120452	0.1564	49
120460	0.1138	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.61	gold quality
left ovary	UBERON:0002119	99.44	gold quality
mucosa of stomach	UBERON:0001199	99.41	gold quality
tibial nerve	UBERON:0001323	99.41	gold quality
right ovary	UBERON:0002118	99.40	gold quality
right lobe of thyroid gland	UBERON:0001119	99.38	gold quality
left uterine tube	UBERON:0001303	99.33	gold quality
endocervix	UBERON:0000458	99.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.32	gold quality
left lobe of thyroid gland	UBERON:0001120	99.31	gold quality
body of uterus	UBERON:0009853	99.31	gold quality
sural nerve	UBERON:0015488	99.30	gold quality
cerebellar hemisphere	UBERON:0002245	99.26	gold quality
left testis	UBERON:0004533	99.25	gold quality
body of pancreas	UBERON:0001150	99.24	gold quality
cerebellar cortex	UBERON:0002129	99.24	gold quality
right testis	UBERON:0004534	99.23	gold quality
metanephros cortex	UBERON:0010533	99.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.21	gold quality
thyroid gland	UBERON:0002046	99.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.17	gold quality
body of stomach	UBERON:0001161	99.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.15	gold quality
lower esophagus	UBERON:0013473	99.14	gold quality
skin of abdomen	UBERON:0001416	99.12	gold quality
minor salivary gland	UBERON:0001830	99.12	gold quality
right lung	UBERON:0002167	99.10	gold quality
ganglionic eminence	UBERON:0004023	99.10	gold quality
granulocyte	CL:0000094	99.09	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	24.16
E-ANND-3	yes	10.87
E-GEOD-137537	no	842.68
E-ENAD-20	no	162.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
AMH	Activation
CYP11A1	Activation
HSD3B2	Unknown
LHB	Unknown
MC2R	Activation
NR0B1	Unknown
SF3B1	Unknown
SOX9	Unknown
STAR	Unknown
SULT2A1	Activation
TCERG1	Repression
U2AF2	Unknown

Upstream regulators (CollecTRI, top): AR, EGR1, EWSR1, FOXC1, FOXL2, MBD2, NR0B1, NR4A1, NR5A1, NR5A2, RLF, SMAD7, SOX9, SP1, TCF21, TCF3, TCF4, USF1, USF2, WT1, ZNF461

miRNA regulators (miRDB)

38 targeting SF1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-4710	98.61	65.96	1048

Literature-anchored findings (GeneRIF, showing 17)

• The KH-QUA2 region of SF1 defines an enlarged KH (hn RNP K) fold which is necessary and sufficient for intron branched point sequence (BPS) binding. (PMID:11691992)
• SF3a60, 66, and 120, but not SF1, are essential for pre-mRNA splicing (PMID:15647371)
• SF1 was essential for the induction of alternative mRNA splicing by the beta-catenin/TCF4 complex. (PMID:17383426)
• SF1 and U2AF form extraspliceosomal complexes before and after taking part in the assembly of catalytic spliceosomes. (PMID:18285458)
• Puf60-UHM binds to ULM sequences in the splicing factors SF1, U2AF65, and SF3b155. (PMID:18974054)
• SF1 silencing affected alternative splicing of endogenous transcripts, establishing a previously unexpected role for SF1 and branch site-like sequences in splice site selection. (PMID:21062807)
• the conformational changes that are induced by assembly of the SF1/U2AF(65)/RNA complex serve to position the pre-mRNA splice site optimally for subsequent stages of splicing. (PMID:21146534)
• central ;mystery’ domain of SF1 crystals belonged to space group C2 and have most probable solvent contents of 64, 52 or 39% with three, four or five molecules per asymmetric unit, respectively (PMID:21505248)
• Findings suggest that Zinc finger motif-1 (ZFM1) is an important factor for the stabilization of a contractile SMC phenotype under basal or mildly activating conditions. (PMID:22906951)
• The conserved SPSP motif phosphorylation and the SF1/U2AF interface are essential in vivo. (PMID:23273425)
• Data suggest that post-translational processing of SF1 (phosphorylation of Ser20) down-regulates nuclear import of SF1 via alterations in kinetic interaction of SF1 nuclear localization signal (NLS) with NLS receptor isoforms. (PMID:25043850)
• Gomafu indirectly modulates the function of the splicing factors SF1 and Celf3 by sequestering these proteins into separate nuclear bodies. (PMID:25145264)
• We demonstrated that PRPF40B interacts directly with SF1 and associates with U2AF(65 (PMID:25605964)
• A novel function of SF1 in the initial recruitment of the U2 snRNP through direct interactions with two U2 snRNP-associated proteins. (PMID:26420826)
• SF1 Phosphorylation Enhances Specific Binding to U2AF(65) and Reduces Binding to 3’-Splice-Site RNA (PMID:28002734)
• Deoxynivalenol globally affects the selection of 3’ splice sites in human cells by suppressing the splicing factors, U2AF1 and SF1. (PMID:31992135)
• Structural basis for the interaction between the first SURP domain of the SF3A1 subunit in U2 snRNP and the human splicing factor SF1. (PMID:36173164)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sf1	ENSDARG00000008188
mus_musculus	Sf1	ENSMUSG00000024949
rattus_norvegicus	Sf1	ENSRNOG00000021085
drosophila_melanogaster	SF1	FBGN0025571
caenorhabditis_elegans		WBGENE00013808

Paralogs (4): KHDRBS2 (ENSG00000112232), QKI (ENSG00000112531), KHDRBS1 (ENSG00000121774), KHDRBS3 (ENSG00000131773)

Protein

Protein identifiers

Splicing factor 1 — Q15637 (reviewed: Q15637)

Alternative names: Mammalian branch point-binding protein, Transcription factor ZFM1, Zinc finger gene in MEN1 locus, Zinc finger protein 162

All UniProt accessions (11): A0A7P0T9U7, A0A9L9PXE4, A0A9L9PXR5, A0A9L9PXU0, C9J792, Q15637, F8WEG7, F8WEV5, H7BZT1, H7C0N4, H7C561

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5’-UACUAAC-3’ of the pre-mRNA. May act as transcription repressor.

Subunit / interactions. Binds U2AF2. Interacts with U1 snRNA. Binds EWSR1, FUS and TAF15. Interacts with RBM17.

Subcellular location. Nucleus.

Tissue specificity. Detected in lung, ovary, adrenal gland, colon, kidney, muscle, pancreas, thyroid, placenta, brain, liver and heart.

Post-translational modifications. Phosphorylation on Ser-20 interferes with U2AF2 binding and spliceosome assembly. Isoform 6 is phosphorylated on Ser-463.

Similarity. Belongs to the BBP/SF1 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q15637-1	1, SF1-HL1	yes
Q15637-2	2, SF1-Bo, Bone
Q15637-3	3, ZFM1-A, ZFM1-ABCDEF
Q15637-4	4, ZFM1-B, ZFM1-ABCDF
Q15637-5	5
Q15637-6	6, ZFM1-D, B6
Q15637-7	7

RefSeq proteins (12): NP_001171501, NP_001171502, NP_001333292, NP_001333293, NP_001333338, NP_001333339, NP_001365885, NP_001365886, NP_004621, NP_973724, NP_973726, NP_973727 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR004087	KH_dom	Domain
IPR032570	SF1-HH	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR045071	BBP-like	Family
IPR047086	SF1-HH_sf	Homologous_superfamily
IPR055256	KH_1_KHDC4/BBP-like	Domain

Pfam: PF00098, PF16275, PF22675

UniProt features (76 total): mutagenesis site 15, helix 12, compositionally biased region 10, modified residue 9, splice variant 8, sequence conflict 6, strand 5, region of interest 3, turn 2, initiator methionine 1, chain 1, domain 1, zinc finger region 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4FXW	X-RAY DIFFRACTION	2.29
4FXX	X-RAY DIFFRACTION	2.48
7VPX	ELECTRON MICROSCOPY	3
1K1G	SOLUTION NMR
1O0P	SOLUTION NMR
1OPI	SOLUTION NMR
2M09	SOLUTION NMR
2M0G	SOLUTION NMR
7VH9	SOLUTION NMR
8PXX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15637-F1	65.28	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 (9): 2, 14, 20, 80, 82, 87, 89, 463, 467

Mutagenesis-validated functional residues (15):

Position	Phenotype
15–17	abolishes interaction with u2af2.
16–18	abolishes interaction with u2af2.
20	strongly decreases interaction with u2af2 and spliceosome assembly.
20	decreases interaction with u2af2.
21	decreases interaction with u2af2 and spliceosome assembly.
21	no effect.
22	abolishes interaction with u2af2.
22	no effect.
151	decreases rna-binding.
160	strongly reduces rna-binding.
184	abolishes rna-binding.
244	decreases rna-binding.
247	decreases rna-binding.
254	slightly decreases rna-binding.
255	slightly decreases rna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 234 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, TGCGCANK_UNKNOWN, GCM_MSN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, HSIAO_HOUSEKEEPING_GENES, TATTATA_MIR374, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, AP2_Q3, BROWNE_HCMV_INFECTION_12HR_UP, chr11q13, BROWNE_HCMV_INFECTION_24HR_UP, GCM_RING1, GGAANCGGAANY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GNF2_FBL

GO Biological Process (9): spliceosomal complex assembly (GO:0000245), mRNA 3’-splice site recognition (GO:0000389), mRNA splicing, via spliceosome (GO:0000398), mRNA cis splicing, via spliceosome (GO:0045292), negative regulation of smooth muscle cell proliferation (GO:0048662), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of DNA-templated transcription (GO:0045892), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (9): transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515), pre-mRNA branch point binding (GO:0045131), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), ribosome (GO:0005840), U2AF complex (GO:0089701)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	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
mRNA splicing, via spliceosome	2
RNA processing	2
binding	2
nuclear protein-containing complex	2
protein-RNA complex assembly	1
mRNA splice site recognition	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
negative regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
mRNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of metabolic process	1
primary metabolic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
nucleic acid binding	1
RNA binding	1
transition metal ion binding	1
protein binding	1
pre-mRNA binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
ribonucleoprotein complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SF1	U2AF2	P26368	993
SF1	U2AF1	Q01081	912
SF1	PYGM	P11217	800
SF1	FKBP2	P26885	774
SF1	PLCB3	Q01970	774
SF1	COX8A	P10176	769
SF1	AHNAK	Q09666	769
SF1	SNRPC	P09234	768
SF1	FTH1	P02794	768
SF1	ROM1	Q03395	767
SF1	MAP3K11	Q16584	767
SF1	CHRM1	P11229	766
SF1	FOSL1	P15407	766
SF1	CAPN1	P07384	766
SF1	SCGB1A1	P11684	765

IntAct

321 interactions, top by confidence:

A	B	Type	Score
FAM168A	SF1	psi-mi:“MI:0915”(physical association)	0.670
CIAO1	SF1	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	SF1	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	SF1	psi-mi:“MI:0915”(physical association)	0.560
SF1	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.560
SF1	TRIM69	psi-mi:“MI:0915”(physical association)	0.560
SF1	CIAO1	psi-mi:“MI:0915”(physical association)	0.560
SF1	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
SF1	MKRN3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP26-1	SF1	psi-mi:“MI:0915”(physical association)	0.560
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
SF1	U2SURP	psi-mi:“MI:0914”(association)	0.350
SF1	KPNA4	psi-mi:“MI:0915”(physical association)	0.000
SF1	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.000
SF1	CEP104	psi-mi:“MI:0915”(physical association)	0.000
SF1	KPNA6	psi-mi:“MI:0915”(physical association)	0.000
U2AF2	SF1	psi-mi:“MI:0915”(physical association)	0.000
RBMS1	SF1	psi-mi:“MI:0915”(physical association)	0.000
SF1	ZFP36L2	psi-mi:“MI:0915”(physical association)	0.000
KPNA2	SF1	psi-mi:“MI:0915”(physical association)	0.000
SF1	KPNA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (460): SF1 (Affinity Capture-MS), SF1 (Two-hybrid), MKRN3 (Two-hybrid), CIAO1 (Two-hybrid), FAM168A (Two-hybrid), TRIM69 (Two-hybrid), KRTAP26-1 (Two-hybrid), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS), SF1 (Affinity Capture-MS)

ESM2 similar proteins: A7EYK3, A7SEP9, A8NYM5, A8XW44, B0JYS7, B7Q2M2, C0NN85, C3Z1P5, C5XYW4, C5XZK6, C7YRT4, D0NHA2, D3ZCL3, D5GDH4, E0VI98, E1C6F0, E2RGI3, E3X5D6, F6HQ26, F6TFD9, F7ARS3, O43670, P09234, P33240, P90815, Q03369, Q05856, Q15637, Q16IW3, Q1K7T5, Q1RLC9, Q298E0, Q32PA0, Q4WQM6, Q56XE4, Q5BBX9, Q5KC16, Q5R8K4, Q5RDA3, Q62241

Diamond homologs: G5EFF1, O01367, O74555, O75525, P0CO44, P0CO45, P13230, Q07666, Q08BJ2, Q0VFL3, Q0WLR1, Q12186, Q15637, Q17339, Q32NN2, Q4P0H7, Q4WXV6, Q54BM5, Q5AED9, Q5VWX1, Q5W9D5, Q5W9D6, Q5W9D7, Q60749, Q64213, Q6BSP4, Q6C187, Q6FW77, Q6IRN2, Q6P0D0, Q6P104, Q750X2, Q75GR5, Q7JJZ8, Q8GWR3, Q8GYR4, Q8NIW7, Q8UUW7, Q91V33, Q91XU1

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
UHMK1	up-regulates	SF1	phosphorylation
SF1	down-regulates	EWSR1	binding
SF1	down-regulates	FUS	binding
EGR1	“up-regulates activity”	SF1	binding
SF1	“up-regulates quantity by expression”	LHB	“transcriptional regulation”
PRKG1	“down-regulates activity”	SF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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
NS1 Mediated Effects on Host Pathways	7	41.6×	9e-08
Maturation of DENV proteins	5	22.0×	2e-04
ISG15 antiviral mechanism	7	21.9×	3e-06
Antimicrobial mechanism of IFN-stimulated genes	5	20.5×	2e-04
Influenza Infection	5	18.3×	4e-04
mRNA Polyadenylation	9	16.5×	5e-07
Interferon Signaling	5	12.5×	2e-03
mRNA Splicing - Major Pathway	9	10.2×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	6	80.2×	2e-08
RNA processing	9	32.8×	3e-09
regulation of alternative mRNA splicing, via spliceosome	7	28.5×	8e-07
protein import into nucleus	8	19.2×	1e-06
mRNA processing	6	7.9×	3e-03
mRNA splicing, via spliceosome	5	7.6×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	90
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1321942	NM_004630.4(SF1):c.221del (p.Pro74fs)	Likely pathogenic
4083510	NM_004630.4(SF1):c.1764_1776del (p.Pro590fs)	Likely pathogenic

SpliceAI

1775 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64766895:CTCA:C	donor_gain	1.0000
11:64766897:CACTT:C	donor_loss	1.0000
11:64766898:A:AC	donor_gain	1.0000
11:64766898:ACTTT:A	donor_loss	1.0000
11:64766899:C:CT	donor_gain	1.0000
11:64766899:CT:C	donor_gain	1.0000
11:64766899:CTT:C	donor_gain	1.0000
11:64766899:CTTT:C	donor_gain	1.0000
11:64766899:CTTTG:C	donor_gain	1.0000
11:64767075:CATAC:C	acceptor_gain	1.0000
11:64767076:ATAC:A	acceptor_gain	1.0000
11:64767077:TAC:T	acceptor_gain	1.0000
11:64767078:AC:A	acceptor_gain	1.0000
11:64767079:CC:C	acceptor_gain	1.0000
11:64767080:C:CC	acceptor_gain	1.0000
11:64767087:CAGG:C	acceptor_gain	1.0000
11:64767088:A:T	acceptor_gain	1.0000
11:64767090:G:C	acceptor_gain	1.0000
11:64767090:G:GC	acceptor_gain	1.0000
11:64767247:CTGAT:C	acceptor_gain	1.0000
11:64767253:T:C	acceptor_gain	1.0000
11:64767253:T:TC	acceptor_gain	1.0000
11:64767256:A:AC	acceptor_gain	1.0000
11:64767256:A:C	acceptor_gain	1.0000
11:64768282:CAGGC:C	acceptor_gain	1.0000
11:64768283:AGGC:A	acceptor_gain	1.0000
11:64768284:GGC:G	acceptor_gain	1.0000
11:64768285:GC:G	acceptor_gain	1.0000
11:64768286:CC:C	acceptor_gain	1.0000
11:64768287:C:CC	acceptor_gain	1.0000

AlphaMissense

4181 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64768212:C:A	G321V	1.000
11:64768213:C:G	G321R	1.000
11:64768215:A:C	L320R	1.000
11:64768215:A:G	L320P	1.000
11:64768215:A:T	L320Q	1.000
11:64768218:T:A	E319V	1.000
11:64768219:C:T	E319K	1.000
11:64768222:C:G	A318P	1.000
11:64768223:C:A	M317I	1.000
11:64768223:C:G	M317I	1.000
11:64768223:C:T	M317I	1.000
11:64768224:A:C	M317R	1.000
11:64768224:A:G	M317T	1.000
11:64768224:A:T	M317K	1.000
11:64768227:A:G	L316P	1.000
11:64768227:A:T	L316H	1.000
11:64768231:A:G	S315P	1.000
11:64768236:T:C	Y313C	1.000
11:64768236:T:G	Y313S	1.000
11:64768237:A:C	Y313D	1.000
11:64768237:A:G	Y313H	1.000
11:64768237:A:T	Y313N	1.000
11:64768239:T:A	E312V	1.000
11:64768239:T:C	E312G	1.000
11:64768240:C:T	E312K	1.000
11:64768245:T:A	D310V	1.000
11:64768245:T:G	D310A	1.000
11:64768246:C:A	D310Y	1.000
11:64768246:C:G	D310H	1.000
11:64768248:A:G	M309T	1.000

dbSNP variants (sampled 300 via entrez): RS1000026483 (11:64774376 G>A), RS1000204579 (11:64778827 C>T), RS1000209348 (11:64778350 G>A,C,T), RS1000260987 (11:64779050 A>G,T), RS1000356158 (11:64773301 C>A,T), RS1000538897 (11:64779754 A>G), RS1000592687 (11:64779963 C>T), RS1000747469 (11:64774849 T>C), RS1000755188 (11:64768527 A>G), RS1000849982 (11:64768905 C>A,G), RS1001096322 (11:64774738 T>A), RS1001333799 (11:64779089 T>G), RS1001591359 (11:64774412 G>C), RS1001627542 (11:64768385 T>C), RS1001701743 (11:64778566 GCGGGGGCGGGC>G,GCGGGGGCGGGCCGGGGGCGGGC)

Disease associations

OMIM: gene MIM:601516 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001163_5	Urate levels	6.000000e-11
GCST90002396_468	Mean reticulocyte volume	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725115 (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
7.09	Kd	81.17	nM	CHEMBL5653589
7.09	ED50	81.17	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	2149381: Binding affinity to human SF1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0812	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases methylation, increases expression, affects cotreatment, decreases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, affects expression (+1 more)	3
bisphenol A	affects expression, affects cotreatment, decreases expression	2
Cisplatin	increases reaction, decreases expression	2
Estradiol	affects binding, increases reaction, increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance, affects expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
hydroxyflutamide	decreases expression	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
triadimefon	increases expression	1
artenimol	affects binding	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
nutlin 3	affects cotreatment, increases secretion	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
jinfukang	decreases expression, increases reaction	1
2,3-dibromopropyl-2,4,6-tribromophenyl ether	decreases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	increases expression	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
CHEMBL5652423	Binding	Binding affinity to human SF1 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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice