SRSF8

Summary

SRSF8 (serine and arginine rich splicing factor 8, HGNC:16988) is a protein-coding gene on chromosome 11q21, encoding Serine/arginine-rich splicing factor 8 (Q9BRL6). Involved in pre-mRNA alternative splicing.

This gene encodes a member of a family of proteins containing a ribonucleoprotein (RNP)-type RNA binding motif and a carboxyl-terminal arginine-serine-rich (RS) domain. The encoded protein functions as a pre-mRNA splicing factor. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10929 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_032102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16988
Approved symbol	SRSF8
Name	serine and arginine rich splicing factor 8
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	SRP46
Ensembl gene	ENSG00000263465
Ensembl biotype	protein_coding
OMIM	603269
Entrez	10929

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000587424, ENST00000638426

RefSeq mRNA: 1 — MANE Select: NM_032102 NM_032102

CCDS: CCDS73370

Canonical transcript exons

ENST00000587424 — 1 exons

Exon	Start	End
ENSE00002942501	95066919	95071225

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0483 / max 178.8464, expressed in 1780 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116300	7.6180	1682
116299	3.7267	1567
116301	1.7244	751
206422	0.9792	650

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.67	gold quality
medial globus pallidus	UBERON:0002477	96.41	gold quality
upper leg skin	UBERON:0004262	96.36	gold quality
middle temporal gyrus	UBERON:0002771	95.90	gold quality
globus pallidus	UBERON:0001875	95.72	gold quality
superficial temporal artery	UBERON:0001614	95.65	gold quality
mammary duct	UBERON:0001765	95.44	gold quality
endothelial cell	CL:0000115	95.35	gold quality
tendon	UBERON:0000043	95.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.26	gold quality
germinal epithelium of ovary	UBERON:0001304	95.12	gold quality
epithelium of mammary gland	UBERON:0003244	95.04	gold quality
gingival epithelium	UBERON:0001949	95.00	gold quality
epithelium of nasopharynx	UBERON:0001951	94.94	gold quality
esophagus squamous epithelium	UBERON:0006920	94.79	gold quality
right coronary artery	UBERON:0001625	94.56	gold quality
gingiva	UBERON:0001828	94.53	gold quality
corpus epididymis	UBERON:0004359	94.52	gold quality
amniotic fluid	UBERON:0000173	94.50	gold quality
penis	UBERON:0000989	94.45	gold quality
adult organism	UBERON:0007023	94.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.35	gold quality
trabecular bone tissue	UBERON:0002483	94.23	gold quality
colonic mucosa	UBERON:0000317	94.08	gold quality
calcaneal tendon	UBERON:0003701	94.08	gold quality
descending thoracic aorta	UBERON:0002345	94.04	gold quality
epithelium of esophagus	UBERON:0001976	94.01	gold quality
caput epididymis	UBERON:0004358	93.92	gold quality
parietal pleura	UBERON:0002400	93.88	gold quality
nephron tubule	UBERON:0001231	93.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

132 targeting SRSF8, 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-8485	100.00	77.57	4731
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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srsf2a	ENSDARG00000057484
danio_rerio	srsf2b	ENSDARG00000103893
drosophila_melanogaster	SC35	FBGN0265298
caenorhabditis_elegans		WBGENE00004701

Paralogs (3): SRSF12 (ENSG00000154548), SRSF2 (ENSG00000161547), SRSF10 (ENSG00000188529)

Protein

Protein identifiers

Serine/arginine-rich splicing factor 8 — Q9BRL6 (reviewed: Q9BRL6)

Alternative names: Pre-mRNA-splicing factor SRP46, Splicing factor, arginine/serine-rich 2B

All UniProt accessions (1): Q9BRL6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA alternative splicing.

Subcellular location. Nucleus.

Tissue specificity. Strongly expressed in pancreas, spleen and prostate. Weakly expressed in lung, liver and thymus.

Similarity. Belongs to the splicing factor SR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BRL6-1	1	yes
Q9BRL6-2	2

RefSeq proteins (1): NP_115285* (*=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 (32 total): compositionally biased region 9, modified residue 9, strand 5, helix 2, initiator methionine 1, chain 1, domain 1, splice variant 1, sequence conflict 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DNM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRL6-F1	57.85	0.09

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, 2, 26, 156, 158, 171, 173, 196, 273

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: 133 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, AAAYRNCTG_UNKNOWN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, WTGAAAT_UNKNOWN, GOBP_RNA_SPLICING, GARY_CD5_TARGETS_DN, ATGCTGG_MIR338

GO Biological Process (3): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), 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
RNA processing	2
binding	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRSF8	SRSF9	Q13242	626
SRSF8	SRSF11	Q05519	618
SRSF8	JMJD4	Q9H9V9	475
SRSF8	USP39	Q53GS9	431
SRSF8	DDX5	P17844	414
SRSF8	SRRM1	Q8IYB3	398
SRSF8	SF3B1	O75533	367
SRSF8	RBM41	Q96IZ5	364
SRSF8	OR8B12	Q8NGG6	357
SRSF8	SMIM19	Q96E16	353
SRSF8	WHRN	Q9P202	349
SRSF8	SNRPA	P09012	345
SRSF8	RBM25	P49756	330
SRSF8	SRSF4	Q08170	330
SRSF8	OR8B3	Q8NGG8	321

IntAct

63 interactions, top by confidence:

A	B	Type	Score
SRPK2	SRSF8	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
LUC7L2	CASC3	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
IL36RN	UBB	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SRSF8	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.520
THRAP3	HNRNPC	psi-mi:“MI:0914”(association)	0.480
U2AF2	U2SURP	psi-mi:“MI:0914”(association)	0.480
Srek1	SRSF8	psi-mi:“MI:0915”(physical association)	0.370
DDX41	DDX39A	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
DOCK8	IPO5	psi-mi:“MI:0914”(association)	0.350
SMIM26	METTL15	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
ERH	BCLAF3	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF320	psi-mi:“MI:0914”(association)	0.350
NXF2B	MEIOC	psi-mi:“MI:0914”(association)	0.350
ADARB1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
FAM120A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PRR3	ZNF316	psi-mi:“MI:0914”(association)	0.350

BioGRID (150): SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Reconstituted Complex), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS), SRSF8 (Affinity Capture-MS)

ESM2 similar proteins: A2RVS6, A6QR16, O02008, O22315, O75494, P19018, P26686, P30352, P62995, P62996, P62997, Q01130, Q06A98, Q08170, Q10021, Q13595, Q15287, Q16629, Q1PDV2, Q28E41, Q3KPW1, Q3MHR5, Q3T106, Q3ZBT6, Q4R5N1, Q52KI8, Q5NVM8, Q5R1W5, Q5R5Q2, Q5XG24, Q5ZMJ9, Q62093, Q6AYK1, Q6PDU1, Q6PFR5, Q6PG31, Q84TH4, Q8BL97, Q8IYB3, Q8RWY7

Diamond homologs: A1C646, A1DGS2, A2R7Z2, A3GGU2, A4QUF0, A4RHN3, A5A6M3, A5DNX9, A5E1Z4, A6SGN8, A6ZZ25, A7EWN6, A7SKE9, A7TFW4, A8NS61, A8WLV5, B0VZS1, B0XS28, B3MSP2, B3MYX2, B3NYY7, B3P935, B4G3E2, B4GUY6, B4I9X1, B4IIC7, B4J4G8, B4JXU2, B4K7S5, B4L710, B4LVR8, B4MA85, B4N1L0, B4NFY1, B4NTY9, B4PP90, B4Q0Y7, B4QS37, C8V330, O35698

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Transport of Mature Transcript to Cytoplasm	6	43.9×	2e-07
mRNA 3’-end processing	10	37.9×	4e-12
Transport of Mature mRNA derived from an Intron-Containing Transcript	11	32.2×	2e-12
mRNA Splicing	14	29.6×	2e-15
RNA Polymerase II Transcription Termination	6	25.3×	4e-06
Processing of Capped Intron-Containing Pre-mRNA	16	25.3×	1e-16
mRNA Polyadenylation	14	23.6×	4e-14
mRNA Splicing - Major Pathway	21	22.1×	5e-21

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	73.5×	6e-10
mRNA splice site recognition	5	55.0×	2e-06
regulation of alternative mRNA splicing, via spliceosome	9	30.1×	2e-09
mRNA splicing, via spliceosome	17	21.3×	7e-16
mRNA export from nucleus	5	20.2×	2e-04
RNA splicing	11	13.3×	5e-08
mRNA processing	9	9.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

108 predictions. Top by Δscore:

Variant	Effect	Δscore
11:95068744:T:TA	acceptor_gain	0.8000
11:95068185:T:TA	donor_gain	0.7100
11:95068186:T:TA	donor_gain	0.6900
11:95067492:T:TA	donor_gain	0.6600
11:95067493:G:GA	donor_gain	0.6400
11:95068187:GT:G	donor_gain	0.6200
11:95068092:G:GT	donor_gain	0.5800
11:95068184:GT:G	donor_gain	0.5600
11:95068648:GCAC:G	acceptor_gain	0.4900
11:95068649:CACC:C	acceptor_gain	0.4900
11:95068650:ACCA:A	acceptor_gain	0.4900
11:95068651:C:G	acceptor_gain	0.4900
11:95067486:TGC:T	donor_gain	0.4700
11:95068144:G:GT	donor_gain	0.4200
11:95068235:G:GA	donor_gain	0.4200
11:95068685:GTT:G	acceptor_gain	0.4200
11:95068651:CC:C	acceptor_gain	0.4100
11:95068650:ACCAG:A	acceptor_gain	0.3900
11:95068655:G:GT	acceptor_gain	0.3900
11:95068656:C:T	acceptor_gain	0.3900
11:95068513:G:GA	donor_gain	0.3800
11:95068645:TGTG:T	acceptor_gain	0.3800
11:95068687:T:TC	acceptor_gain	0.3500
11:95068647:TG:T	acceptor_gain	0.3400
11:95068650:A:AG	acceptor_gain	0.3300
11:95068209:TGCCA:T	donor_gain	0.3200
11:95068210:GCCAG:G	donor_gain	0.3200
11:95068234:TGGCA:T	donor_gain	0.3200
11:95068684:GGTTA:G	acceptor_gain	0.3200
11:95068686:TTA:T	acceptor_gain	0.3200

AlphaMissense

1776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:95067339:G:A	G38E	1.000
11:95067339:G:T	G38V	1.000
11:95067395:T:C	F57L	1.000
11:95067396:T:C	F57S	1.000
11:95067397:C:A	F57L	1.000
11:95067397:C:G	F57L	1.000
11:95067401:T:C	F59L	1.000
11:95067402:T:C	F59S	1.000
11:95067402:T:G	F59C	1.000
11:95067403:C:A	F59L	1.000
11:95067403:C:G	F59L	1.000
11:95067405:T:A	V60D	1.000
11:95067410:T:C	F62L	1.000
11:95067411:T:C	F62S	1.000
11:95067412:T:A	F62L	1.000
11:95067412:T:G	F62L	1.000
11:95067273:T:A	L16H	0.999
11:95067277:G:C	K17N	0.999
11:95067277:G:T	K17N	0.999
11:95067315:T:C	L30S	0.999
11:95067326:T:A	F34I	0.999
11:95067326:T:C	F34L	0.999
11:95067327:T:C	F34S	0.999
11:95067328:C:A	F34L	0.999
11:95067328:C:G	F34L	0.999
11:95067338:G:T	G38W	0.999
11:95067393:G:A	G56D	0.999
11:95067399:C:A	A58D	0.999
11:95067401:T:A	F59I	0.999
11:95067411:T:G	F62C	0.999

dbSNP variants (sampled 300 via entrez): RS1000083272 (11:95070262 G>A), RS1002448043 (11:95065282 T>A,C), RS1004931293 (11:95067753 G>C,T), RS1005344586 (11:95071609 T>C), RS1006201696 (11:95066090 G>T), RS1006578306 (11:95066698 C>A), RS1006900199 (11:95070224 C>A,T), RS1007014948 (11:95069920 G>C,T), RS1007047610 (11:95069778 A>G), RS1009346479 (11:95065229 T>C), RS1009728129 (11:95065475 G>A), RS1010240471 (11:95067384 C>A,T), RS1011151923 (11:95070405 A>C), RS1012706162 (11:95069298 C>T), RS1013491202 (11:95065623 C>A,T)

Disease associations

OMIM: gene MIM:603269 | 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
GCST90025872_11	Chronic widespread musculoskeletal pain	9.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010099	chronic widespread pain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	3
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
Formaldehyde	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Vanadates	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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