SRSF12

Summary

SRSF12 (serine and arginine rich splicing factor 12, HGNC:21220) is a protein-coding gene on chromosome 6q15, encoding Serine/arginine-rich splicing factor 12 (Q8WXF0). Splicing factor that seems to antagonize SR proteins in pre-mRNA splicing regulation.

Enables RNA binding activity. Involved in mRNA 5’-splice site recognition and regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in nuclear speck.

Source: NCBI Gene 135295 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• MANE Select transcript: NM_080743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21220
Approved symbol	SRSF12
Name	serine and arginine rich splicing factor 12
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	SRrp35, SFRS19
Ensembl gene	ENSG00000154548
Ensembl biotype	protein_coding
Entrez	135295

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 nonsense_mediated_decay, 2 protein_coding, 2 retained_intron

ENST00000452027, ENST00000475068, ENST00000488604, ENST00000517387, ENST00000524221, ENST00000850585, ENST00000850586

RefSeq mRNA: 4 — MANE Select: NM_080743 NM_001376896, NM_001376897, NM_001376898, NM_080743

CCDS: CCDS47459

Canonical transcript exons

ENST00000452027 — 5 exons

Exon	Start	End
ENSE00001826444	89107154	89107258
ENSE00004282225	89095959	89098947
ENSE00004282227	89105119	89105260
ENSE00004282230	89117823	89118071
ENSE00004282231	89105427	89105530

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 87.79.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9305 / max 37.1872, expressed in 551 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74678	0.9858	402
74679	0.9446	472

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.79	gold quality
cortical plate	UBERON:0005343	87.10	gold quality
oocyte	CL:0000023	86.87	gold quality
sperm	CL:0000019	85.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.75	gold quality
left testis	UBERON:0004533	84.51	gold quality
right testis	UBERON:0004534	84.02	gold quality
testis	UBERON:0000473	83.91	gold quality
ganglionic eminence	UBERON:0004023	83.77	gold quality
ventricular zone	UBERON:0003053	83.35	gold quality
cartilage tissue	UBERON:0002418	78.91	gold quality
secondary oocyte	CL:0000655	77.73	gold quality
prefrontal cortex	UBERON:0000451	77.18	gold quality
anterior cingulate cortex	UBERON:0009835	76.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.43	gold quality
islet of Langerhans	UBERON:0000006	75.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.87	gold quality
right frontal lobe	UBERON:0002810	75.77	gold quality
neocortex	UBERON:0001950	75.17	gold quality
pancreatic ductal cell	CL:0002079	75.11	gold quality
cerebellar cortex	UBERON:0002129	74.53	gold quality
cerebellar hemisphere	UBERON:0002245	74.53	gold quality
frontal cortex	UBERON:0001870	74.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.79	gold quality
amygdala	UBERON:0001876	73.66	gold quality
cerebral cortex	UBERON:0000956	73.65	gold quality
cerebellum	UBERON:0002037	73.40	gold quality
hypothalamus	UBERON:0001898	73.21	gold quality
buccal mucosa cell	CL:0002336	72.76	silver quality
primary visual cortex	UBERON:0002436	72.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting SRSF12, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-7153-5P	99.94	68.89	1006

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srsf10a	ENSDARG00000112572
mus_musculus	Srsf12	ENSMUSG00000054679
rattus_norvegicus	Srsf12	ENSRNOG00000069984

Paralogs (3): SRSF2 (ENSG00000161547), SRSF10 (ENSG00000188529), SRSF8 (ENSG00000263465)

Protein

Protein identifiers

Serine/arginine-rich splicing factor 12 — Q8WXF0 (reviewed: Q8WXF0)

Alternative names: 35 kDa SR repressor protein, Splicing factor, arginine/serine-rich 13B, Splicing factor, arginine/serine-rich 19

All UniProt accessions (3): Q8WXF0, E5RFT0, E5RJS0

UniProt curated annotations — full annotation on UniProt →

Function. Splicing factor that seems to antagonize SR proteins in pre-mRNA splicing regulation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis.

Similarity. Belongs to the splicing factor SR family.

RefSeq proteins (4): NP_001363825, NP_001363826, NP_001363827, NP_542781* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050441	RBM	Family

Pfam: PF00076

UniProt features (11 total): compositionally biased region 6, sequence conflict 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXF0-F1	63.01	0.25

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9770562	mRNA Polyadenylation
R-HSA-72172	mRNA Splicing
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 110 (showing top): chr6q15, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, MODULE_511, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, GOBP_MRNA_SPLICE_SITE_RECOGNITION, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_MRNA_CIS_SPLICING_VIA_SPLICEOSOME, BIDUS_METASTASIS_UP, LIEN_BREAST_CARCINOMA_METAPLASTIC_VS_DUCTAL_UP

GO Biological Process (6): spliceosomal tri-snRNP complex assembly (GO:0000244), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA 5’-splice site recognition (GO:0000395), negative regulation of mRNA splicing, via spliceosome (GO:0048025), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), RS domain binding (GO:0050733), obsolete unfolded protein binding (GO:0051082), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Processing of Capped Intron-Containing Pre-mRNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of mRNA splicing, via spliceosome	2
RNA processing	2
binding	2
spliceosomal snRNP assembly	1
alternative mRNA splicing, via spliceosome	1
mRNA splice site recognition	1
mRNA cis splicing, via spliceosome	1
mRNA splicing, via spliceosome	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
protein domain specific binding	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRSF12	FUS	P35637	654
SRSF12	SRSF11	Q05519	644
SRSF12	SRSF9	Q13242	588
SRSF12	SRSF1	Q07955	496
SRSF12	CD44	P16070	436
SRSF12	RBM47	A0AV96	405
SRSF12	ESRP2	Q9H6T0	398
SRSF12	PPP1R14C	Q8TAE6	392
SRSF12	SFSWAP	Q12872	389
SRSF12	PSIP1	O75475	386
SRSF12	ZCCHC24	Q8N2G6	380
SRSF12	USP49	Q70CQ1	374
SRSF12	SON	P18583	371
SRSF12	ESRP1	Q6NXG1	362
SRSF12	CT83	Q5H943	348

IntAct

153 interactions, top by confidence:

A	B	Type	Score
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SRPK2	SRSF12	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
RPL7	ZBTB24	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ZNF689	ZNF593	psi-mi:“MI:0914”(association)	0.530
LUC7L2	CASC3	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
U2AF2	U2SURP	psi-mi:“MI:0914”(association)	0.480
SRSF12	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (156): SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS)

ESM2 similar proteins: A2AR02, O02008, O13845, O35986, O55035, O75494, P0C196, P11596, P19018, P30352, P30415, P62995, P62996, P62997, P92965, Q05AT9, Q10193, Q10B98, Q13595, Q19QU3, Q1ECZ9, Q1MTR2, Q1PDV2, Q23935, Q24669, Q24761, Q3UC65, Q3ZBT6, Q4P4G8, Q4R626, Q5R1W5, Q5U2S0, Q62504, Q6C0M9, Q6PFR5, Q84TH4, Q8R0F5, Q8VY74, Q8W4D8, Q8WXF0

Diamond homologs: A2Y0J7, A5A6M3, A6NDE4, A6NEQ0, B8AM21, O22922, O74968, O75494, P08579, P09012, P0C7P1, P0DJD3, P0DJD4, P38159, P40567, P43332, P45429, P59708, Q06AA4, Q0DKM4, Q10MR0, Q15415, Q2KIR1, Q39244, Q4R7F0, Q4V898, Q54J05, Q62189, Q6IRQ4, Q7LL14, Q7ZWA3, Q8H1S6, Q8ITY4, Q8WXF0, Q91VM5, Q9CQI7, Q9FMP4, Q9R0U0, Q9WV02, Q9Y3B4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	34.3×	8e-06
Transport of Mature Transcript to Cytoplasm	7	27.2×	3e-07
mRNA 3’-end processing	10	20.1×	4e-09
Transport of Mature mRNA derived from an Intron-Containing Transcript	11	17.1×	3e-09
RHO GTPases activate PKNs	5	16.2×	2e-04
RNA Polymerase II Transcription Termination	7	15.7×	8e-06
mRNA Splicing	13	14.6×	6e-10
SARS-CoV-1-host interactions	8	14.3×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	31.3×	9e-06
regulation of mRNA splicing, via spliceosome	5	30.2×	7e-05
spliceosomal complex assembly	5	20.5×	4e-04
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	15.9×	1e-03
regulation of alternative mRNA splicing, via spliceosome	8	13.3×	2e-05
mRNA export from nucleus	6	12.1×	8e-04
mRNA splicing, via spliceosome	17	10.6×	3e-10
rRNA processing	8	7.7×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1054 predictions. Top by Δscore:

Variant	Effect	Δscore
6:89105111:ATACT:A	donor_gain	1.0000
6:89105113:A:AC	donor_gain	1.0000
6:89105114:C:CC	donor_gain	1.0000
6:89105114:CTCA:C	donor_gain	1.0000
6:89105115:TCA:T	donor_loss	1.0000
6:89105116:CACT:C	donor_loss	1.0000
6:89105117:A:AC	donor_gain	1.0000
6:89105117:ACT:A	donor_gain	1.0000
6:89105118:C:CG	donor_gain	1.0000
6:89105118:CT:C	donor_gain	1.0000
6:89105118:CTC:C	donor_gain	1.0000
6:89105118:CTCT:C	donor_gain	1.0000
6:89105118:CTCTT:C	donor_gain	1.0000
6:89105256:TGGTG:T	acceptor_gain	1.0000
6:89105258:GTG:G	acceptor_gain	1.0000
6:89105259:TG:T	acceptor_gain	1.0000
6:89105261:C:CC	acceptor_gain	1.0000
6:89105425:A:AC	donor_gain	1.0000
6:89105426:C:CC	donor_gain	1.0000
6:89105888:A:AC	donor_gain	1.0000
6:89105888:ACTC:A	donor_gain	1.0000
6:89105889:C:CC	donor_gain	1.0000
6:89105889:CTCC:C	donor_gain	1.0000
6:89105891:C:CA	donor_gain	1.0000
6:89107269:T:C	acceptor_gain	1.0000
6:89117842:T:A	donor_gain	1.0000
6:89105151:T:TA	donor_gain	0.9900
6:89105152:C:A	donor_gain	0.9900
6:89105254:CCTGG:C	acceptor_gain	0.9900
6:89105257:GGTG:G	acceptor_gain	0.9900

AlphaMissense

1664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:89105248:A:G	M96T	1.000
6:89105428:T:A	K91N	1.000
6:89105428:T:G	K91N	1.000
6:89105433:G:T	R90S	1.000
6:89105446:A:C	F85L	1.000
6:89105446:A:T	F85L	1.000
6:89105447:A:G	F85S	1.000
6:89105448:A:G	F85L	1.000
6:89105453:A:C	I83R	1.000
6:89105453:A:T	I83K	1.000
6:89105465:C:G	R79P	1.000
6:89105489:A:G	L71P	1.000
6:89105501:G:T	A67D	1.000
6:89105510:G:T	A64D	1.000
6:89105511:C:G	A64P	1.000
6:89105527:A:C	F58L	1.000
6:89105527:A:T	F58L	1.000
6:89105528:A:G	F58S	1.000
6:89105529:A:G	F58L	1.000
6:89107157:A:T	V56D	1.000
6:89107163:G:T	A54D	1.000
6:89107165:A:C	F53L	1.000
6:89107165:A:T	F53L	1.000
6:89107166:A:G	F53S	1.000
6:89107167:A:G	F53L	1.000
6:89107169:C:T	G52E	1.000
6:89107171:T:A	R51S	1.000
6:89107171:T:G	R51S	1.000
6:89107199:G:T	P42Q	1.000
6:89107208:A:T	V39D	1.000

dbSNP variants (sampled 300 via entrez): RS1000106183 (6:89115385 C>A,T), RS1000507272 (6:89105718 T>C,G), RS1000613820 (6:89106262 G>A), RS1000833986 (6:89117563 C>T), RS1001155068 (6:89116487 A>C,G), RS1001222837 (6:89106107 A>G), RS1001284477 (6:89117334 G>C,T), RS1001399799 (6:89099940 T>G), RS1001445534 (6:89115837 G>A), RS1001808722 (6:89118099 C>A,G,T), RS1001952655 (6:89111883 T>G), RS1002052941 (6:89111466 TAATA>T), RS1002092251 (6:89106025 A>C), RS1002499619 (6:89116814 G>A), RS1002549449 (6:89105656 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012020_120	Serum metabolite levels	7.000000e-23

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Lipopolysaccharides	increases expression, affects response to substance	1
Ribonucleotides	affects binding	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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