SRSF6

Summary

SRSF6 (serine and arginine rich splicing factor 6, HGNC:10788) is a protein-coding gene on chromosome 20q13.11, encoding Serine/arginine-rich splicing factor 6 (Q13247). Plays a role in constitutive splicing and modulates the selection of alternative splice sites. It is a selective cancer dependency (DepMap: 78.1% of cell lines).

The protein encoded by this gene is involved in mRNA splicing and may play a role in the determination of alternative splicing. The encoded nuclear protein belongs to the splicing factor SR family and has been shown to bind with and modulate another member of the family, SFRS12. Alternative splicing results in multiple transcript variants. In addition, two pseudogenes, one on chromosome 17 and the other on the X chromosome, have been found for this gene.

Source: NCBI Gene 6431 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 78.1% of screened cell lines
• MANE Select transcript: NM_006275

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10788
Approved symbol	SRSF6
Name	serine and arginine rich splicing factor 6
Location	20q13.11
Locus type	gene with protein product
Status	Approved
Aliases	SRP55, B52
Ensembl gene	ENSG00000124193
Ensembl biotype	protein_coding
OMIM	601944
Entrez	6431

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000244020, ENST00000483871, ENST00000662078, ENST00000668808, ENST00000670741, ENST00000671022, ENST00000945325

RefSeq mRNA: 1 — MANE Select: NM_006275 NM_006275

CCDS: CCDS13318

Canonical transcript exons

ENST00000244020 — 6 exons

Exon	Start	End
ENSE00000844820	43458361	43458509
ENSE00003460251	43460515	43460598
ENSE00003564571	43459771	43459895
ENSE00003600529	43460033	43460241
ENSE00003606849	43460703	43464243
ENSE00003845404	43457896	43458140

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 128.4620 / max 2378.6710, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184657	103.3142	1825
184659	23.0298	1756
184655	1.5962	1069
184656	0.5218	284

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.16	gold quality
body of pancreas	UBERON:0001150	98.90	gold quality
right lobe of thyroid gland	UBERON:0001119	98.77	gold quality
right adrenal gland cortex	UBERON:0035827	98.75	gold quality
right ovary	UBERON:0002118	98.72	gold quality
left lobe of thyroid gland	UBERON:0001120	98.71	gold quality
right adrenal gland	UBERON:0001233	98.67	gold quality
left ovary	UBERON:0002119	98.66	gold quality
thyroid gland	UBERON:0002046	98.59	gold quality
germinal epithelium of ovary	UBERON:0001304	98.58	gold quality
ventricular zone	UBERON:0003053	98.54	gold quality
metanephros cortex	UBERON:0010533	98.54	gold quality
ovary	UBERON:0000992	98.45	gold quality
tibia	UBERON:0000979	98.41	gold quality
left adrenal gland	UBERON:0001234	98.41	gold quality
minor salivary gland	UBERON:0001830	98.41	gold quality
gall bladder	UBERON:0002110	98.39	gold quality
parietal pleura	UBERON:0002400	98.37	gold quality
endocervix	UBERON:0000458	98.34	gold quality
left adrenal gland cortex	UBERON:0035825	98.33	gold quality
right lobe of liver	UBERON:0001114	98.29	gold quality
pituitary gland	UBERON:0000007	98.28	gold quality
calcaneal tendon	UBERON:0003701	98.28	gold quality
rectum	UBERON:0001052	98.26	gold quality
body of uterus	UBERON:0009853	98.22	gold quality
adrenal cortex	UBERON:0001235	98.19	gold quality
body of stomach	UBERON:0001161	98.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.18	gold quality
monocyte	CL:0000576	98.12	gold quality
pleura	UBERON:0000977	98.11	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	4.77
E-MTAB-7249	no	4868.37
E-GEOD-98556	no	4774.09
E-MTAB-6819	no	1928.46
E-MTAB-10137	no	979.27
E-GEOD-93593	no	6.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting SRSF6, 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-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-7153-5P	99.94	68.89	1006

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 32)

• interacts with calcitonin/CGRP exon 4 exonic splice enhancer(ESE); binding of SRp55 to an ESE required for calcitonin mRNA splicing suggests that the different levels of SRp55 in different cell types may regulate calcitonin/CGRP alternative splicing (PMID:12531473)
• SRp55 binding to a suboptimal RNA binding site in the calcitonin/CGRP pre-mRNA exonic splice enhancer, or increasing the amount of SRp55 in cells, is required for calcitonin mRNA production. (PMID:12549914)
• Higher relative expression of SR55 protein in breast tumors was associated with altered pattern of CD44 variants incorporating exon v7 (PMID:12779084)
• ASF/SF2 and SRp55 appear to interact with the variable TF exon 5 through exonic splicing enhancers at bases 39 and 87-117. Weakening of the above ESE modulates splicing of TF exon 5. (PMID:18315555)
• These findings show that modulation of splicing activity in p53-deficient cells during the early response to sub-lethal DNA damage results in a change in the splicing of target genes, thus modifying the cellular response to genotoxic agents. (PMID:18571879)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Here, the authors report that specific SR proteins, particularly SRp40 and SRp55, promote human immunodeficiency virus type 1 (HIV-1) Gag translation from unspliced (intron-containing) viral RNA. (PMID:20427542)
• Serine- and arginine-rich proteins 55 and 75 (SRp55 and SRp75) induce production of HIV-1 vpr mRNA by inhibiting the 5’-splice site of exon 3. (PMID:20685659)
• SRp55 aids in the generation of partially spliced and unspliced HIV-1 mRNAs. (PMID:21345357)
• Report upregulation of Bim and the splicing factor SRp55 in melanoma cells from patients treated with selective BRAF inhibitors. (PMID:22516966)
• Phosphorylation of SRp55 by Dyrk1A suppressed its ability to promote Tau exon 10 inclusion. (PMID:22767602)
• The splicing factor SRSF6 is an oncoprotein that regulates the proliferation and survival of lung and colon cancer cells. (PMID:23132731)
• Zinc inhibits the activity of SRSF6 and promotes elimination of exon 4, leading to preferential generation of BimS. (PMID:23648111)
• SRSF6 is a regulator of wound healing and tissue homeostasis in skin. (PMID:24440982)
• The authors propose that splicing at 3’ss A3 is dependent on binding of the enhancing SR proteins SRSF2 and SRSF6 to the HIV-1 tat ESE and ESE2 sequence. (PMID:25889056)
• LINC01133 inhibits epithelial mesenchymal transformation and metastasis in colorectal neoplasms by directly binding to SRSF6 as a target mimic. (PMID:27443606)
• The recent studies suggest that correcting the SRSF6-driven missplicing and/or microtubule-associated imbalance might be of therapeutic value in Huntington’s disease. (PMID:27529534)
• SRSF6 functions the important roles in mediating CRC progression through regulating AS, and indacaterol is repositioned as an antitumour drug through targeting SRSF6. (PMID:29114070)
• Data suggest that regulation of pancreatic beta-cell function and survival/apoptosis involves alternative splicing modulated by key splicing regulator SRP55; SRP55-regulated alternative splicing includes modulation of function of pro-apoptotic proteins (BIM, BAX), JNK signaling, and endoplasmic reticulum stress. (BIM = BCL-2 interacting protein BIM; BAX = apoptosis regulator BAX) (PMID:29246973)
• Results identified SRSF6 protein as one of the factors involved in modulating the splicing of the DDC mutated (c.714+4A>T) transcript. (PMID:30260058)
• Data indicate the extent of inter-individual variation in myocardial dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A)-serine and arginine rich splicing factor 6 (SRSF6)-troponin T2, cardiac type protein (TNNT2) expression in the context of Down syndrome. (PMID:31201803)
• Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia. (PMID:32444465)
• Silencing Srsf6 does not modulate incomplete splicing of the huntingtin gene in Huntington’s disease models. (PMID:32820193)
• SRSF6 regulates alternative splicing of genes involved in DNA damage response and DNA repair in HeLa cells. (PMID:32901876)
• Relative strength of 5’ splice-site strength defines functions of SRSF2 and SRSF6 in alternative splicing of Bcl-x pre-mRNA. (PMID:33050987)
• The RNA-binding profile of the splicing factor SRSF6 in immortalized human pancreatic beta-cells. (PMID:33376132)
• LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM. (PMID:33397371)
• Splicing factor SRSF6 mediates pleural fibrosis. (PMID:33905374)
• DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing. (PMID:34614409)
• A candidate gene study reveals association between a variant of the SRp55 splicing factor gene and systemic sclerosis. (PMID:34665708)
• Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia. (PMID:36620874)
• Genetic compensation response could exist in colorectal cancer: UPF3A upregulates the oncogenic homologue gene SRSF3 expression corresponding to SRSF6 to promote colorectal cancer metastasis. (PMID:36807382)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srsf6a	ENSDARG00000013729
danio_rerio	srsf6b	ENSDARG00000016783
mus_musculus	Srsf6	ENSMUSG00000016921
rattus_norvegicus	Srsf6	ENSRNOG00000006380

Paralogs (8): SRSF5 (ENSG00000100650), RSRC2 (ENSG00000111011), SRSF9 (ENSG00000111786), SRSF3 (ENSG00000112081), SRSF7 (ENSG00000115875), SRSF4 (ENSG00000116350), RSRP1 (ENSG00000117616), SRSF1 (ENSG00000136450)

Protein

Protein identifiers

Serine/arginine-rich splicing factor 6 — Q13247 (reviewed: Q13247)

Alternative names: Pre-mRNA-splicing factor SRP55, Splicing factor, arginine/serine-rich 6

All UniProt accessions (4): A0A590UJK4, A0A590UJP7, A0A590UK01, Q13247

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in constitutive splicing and modulates the selection of alternative splice sites. Plays a role in the alternative splicing of MAPT/Tau exon 10. Binds to alternative exons of TNC pre-mRNA and promotes the expression of alternatively spliced TNC. Plays a role in wound healing and in the regulation of keratinocyte differentiation and proliferation via its role in alternative splicing.

Subunit / interactions. Binds SREK1/SFRS12. Interacts with DYRK1A.

Subcellular location. Nucleus. Nucleus speckle.

Post-translational modifications. Extensively phosphorylated on serine residues in the RS domain. Phosphorylated by DYRK1A, probably in the RS domain. Phosphorylation by DYRK1A modulates alternative splice site selection and inhibits the expression of MAPT/Tau exon 10.

Similarity. Belongs to the splicing factor SR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13247-1	SRP55-1	yes
Q13247-2	SRP55-2
Q13247-3	SRP55-3

RefSeq proteins (1): NP_006266* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034511	SRSF6_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR047190	RRM2_SRSF4/6	Domain
IPR050374	RRT5_SRSF_SR	Family

Pfam: PF00076

UniProt features (27 total): modified residue 9, compositionally biased region 4, splice variant 3, mutagenesis site 3, domain 2, region of interest 2, chain 1, cross-link 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9HX8	X-RAY DIFFRACTION	2
9HX5	X-RAY DIFFRACTION	2.1
9HX7	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13247-F1	62.62	0.00

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 (10): 81, 84, 165, 297, 299, 303, 314, 316, 182, 45

Mutagenesis-validated functional residues (3):

Position	Phenotype
280	no effect on regulation of alternative splicing of mapt/tau exon 10 by dyrk1a.
303	abolishes regulatory effect of dyrk1a on alternative splicing of mapt/tau exon 10.
316	no effect on regulation of alternative splicing of mapt/tau exon 10 by dyrk1a.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-72172	mRNA Splicing
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 426 (showing top): MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, JI_RESPONSE_TO_FSH_UP, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, PAL_PRMT5_TARGETS_UP, GOBP_KERATINOCYTE_PROLIFERATION, TTTGTAG_MIR520D, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING

GO Biological Process (14): alternative mRNA splicing, via spliceosome (GO:0000380), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splice site recognition (GO:0006376), regulation of keratinocyte proliferation (GO:0010837), response to insulin (GO:0032868), negative regulation of keratinocyte differentiation (GO:0045617), negative regulation of mRNA splicing, via spliceosome (GO:0048025), positive regulation of epithelial cell proliferation involved in lung morphogenesis (GO:0060501), regulation of wound healing (GO:0061041), negative regulation of type B pancreatic cell apoptotic process (GO:2000675), RNA splicing, via transesterification reactions (GO:0000375), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of gene expression (GO:0010629)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), pre-mRNA binding (GO:0036002), 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-8 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	3
mRNA Splicing	2
Transport of Mature Transcript to Cytoplasm	1
Metabolism of RNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA splicing, via spliceosome	2
regulation of mRNA splicing, via spliceosome	2
RNA processing	2
RNA binding	2
binding	2
alternative mRNA splicing, via spliceosome	1
spliceosomal complex assembly	1
protein-RNA complex assembly	1
keratinocyte proliferation	1
regulation of epithelial cell proliferation	1
response to peptide hormone	1
keratinocyte differentiation	1
negative regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
negative regulation of multicellular organismal process	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
positive regulation of epithelial cell proliferation	1
epithelial cell proliferation involved in lung morphogenesis	1
regulation of epithelial cell proliferation involved in lung morphogenesis	1
wound healing	1
regulation of response to wounding	1
type B pancreatic cell apoptotic process	1
negative regulation of epithelial cell apoptotic process	1
regulation of type B pancreatic cell apoptotic process	1
RNA splicing	1
mRNA metabolic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
nucleic acid binding	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRSF6	U2AF2	P26368	789
SRSF6	TRA2B	P62995	707
SRSF6	SRPK1	Q96SB4	685
SRSF6	SRSF11	Q05519	672
SRSF6	HNRNPK	P61978	658
SRSF6	SREK1	Q8WXA9	650
SRSF6	HLA-B	P01889	648
SRSF6	HNRNPA1	P09651	640
SRSF6	MAPT	P10636	617
SRSF6	SRSF3	P23152	599
SRSF6	HNRNPDL	O14979	598
SRSF6	HNRNPC	P07910	584
SRSF6	SRRM1	Q8IYB3	584
SRSF6	HNRNPH1	P31943	575
SRSF6	SRSF4	Q08170	575

IntAct

261 interactions, top by confidence:

A	B	Type	Score
CDKN2A	CDK4	psi-mi:“MI:0914”(association)	0.960
LUC7L2	SRSF6	psi-mi:“MI:0915”(physical association)	0.780
SRSF6	LUC7L2	psi-mi:“MI:0915”(physical association)	0.780
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
NHP2	DKC1	psi-mi:“MI:0914”(association)	0.730
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
SRSF6	SRSF4	psi-mi:“MI:0915”(physical association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
COMMD6	VPS26C	psi-mi:“MI:0914”(association)	0.640
DHX8	AHCYL1	psi-mi:“MI:0914”(association)	0.640
PNN	SAP18	psi-mi:“MI:0914”(association)	0.620
SRSF6	LUC7L	psi-mi:“MI:0915”(physical association)	0.560
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
HP1BP3	IPO8	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
RBM7	HTATSF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (646): SRSF6 (Affinity Capture-MS), LUC7L2 (Two-hybrid), SRSF6 (Affinity Capture-MS), SRSF6 (Affinity Capture-MS), SRSF6 (Affinity Capture-MS), SRSF6 (Affinity Capture-MS), SRSF6 (Affinity Capture-MS), SRSF6 (Affinity Capture-MS), RNPS1 (Two-hybrid), SRSF6 (Two-hybrid), SRSF6 (Affinity Capture-MS), ATL3 (Co-fractionation), RBBP4 (Co-fractionation), RNPS1 (Co-fractionation), SRSF1 (Co-fractionation)

ESM2 similar proteins: A2RVS6, A6QR16, G3V6S8, O22315, O35326, P08621, P09406, P26686, P30352, P62995, P62996, P62997, P84104, Q01130, Q06A98, Q08170, Q09167, Q10021, Q13243, Q13247, Q13595, Q15287, Q16629, Q18409, Q1RMR2, Q23120, Q23121, Q28E41, Q3B7L6, Q3KPW1, Q3MHR5, Q3T106, Q3TWW8, Q3ZBT6, Q4R5N1, Q5NVM8, Q5R1W5, Q5XG24, Q62093, Q62376

Diamond homologs: A0A0D1C8Z4, A0A0D1DZT6, A2RVS6, A5DM21, A5DW14, B5FXN8, F1QB54, F4HT49, F4I3B3, F4JHI7, G3V6S8, O08583, O13845, O22315, O35326, O59670, O74400, P04147, P19682, P19683, P19684, P20965, P49313, P49314, P78814, P82277, P97855, Q04836, Q08170, Q08935, Q08937, Q09167, Q13242, Q13243, Q13247, Q13283, Q14498, Q1ZXC2, Q28FB9, Q32LC7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DYRK1A	“up-regulates activity”	SRSF6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 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	10	25.6×	9e-11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	18.2×	1e-20
Peptide chain elongation	21	17.9×	5e-19
Viral mRNA Translation	21	17.9×	5e-19
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	21	17.7×	6e-19
Nonsense-Mediated Decay (NMD)	11	17.2×	7e-10
Selenocysteine synthesis	21	16.9×	1e-18
Eukaryotic Translation Termination	21	16.9×	1e-18

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription by RNA polymerase III	5	24.5×	1e-04
cytoplasmic translation	22	21.3×	2e-20
negative regulation of mRNA splicing, via spliceosome	5	20.1×	3e-04
ribosomal large subunit biogenesis	8	18.6×	1e-06
ribosome biogenesis	5	16.3×	6e-04
regulation of alternative mRNA splicing, via spliceosome	12	15.3×	5e-09
translation	25	13.4×	1e-18
mRNA export from nucleus	8	12.4×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

654 predictions. Top by Δscore:

Variant	Effect	Δscore
20:43458121:G:GT	donor_gain	1.0000
20:43458138:TGG:T	donor_gain	1.0000
20:43458139:GG:G	donor_gain	1.0000
20:43458139:GGG:G	donor_gain	1.0000
20:43458140:GG:G	donor_gain	1.0000
20:43458496:C:G	donor_gain	1.0000
20:43458501:G:GT	donor_gain	1.0000
20:43458505:CCGCA:C	donor_gain	1.0000
20:43458506:CGCA:C	donor_gain	1.0000
20:43458507:GCA:G	donor_gain	1.0000
20:43458507:GCAG:G	donor_gain	1.0000
20:43458508:CA:C	donor_gain	1.0000
20:43458510:G:GG	donor_gain	1.0000
20:43459760:ATGT:A	acceptor_gain	1.0000
20:43459761:T:G	acceptor_gain	1.0000
20:43459763:T:TA	acceptor_gain	1.0000
20:43459768:AAGGT:A	acceptor_gain	1.0000
20:43459769:AGGT:A	acceptor_gain	1.0000
20:43459770:GGTG:G	acceptor_gain	1.0000
20:43459891:TAAAG:T	donor_loss	1.0000
20:43459893:AAGG:A	donor_loss	1.0000
20:43459896:GT:G	donor_loss	1.0000
20:43460028:TTCA:T	acceptor_loss	1.0000
20:43460031:A:AG	acceptor_gain	1.0000
20:43460031:AG:A	acceptor_gain	1.0000
20:43460032:G:GG	acceptor_gain	1.0000
20:43460032:GG:G	acceptor_gain	1.0000
20:43460032:GGA:G	acceptor_gain	1.0000
20:43460032:GGAT:G	acceptor_gain	1.0000
20:43460032:GGATT:G	acceptor_gain	1.0000

AlphaMissense

2195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:43458044:T:A	V4D	1.000
20:43458046:T:C	Y5H	1.000
20:43458050:T:A	I6K	1.000
20:43458052:G:A	G7R	1.000
20:43458052:G:C	G7R	1.000
20:43458053:G:A	G7E	1.000
20:43458053:G:T	G7V	1.000
20:43458059:T:A	L9Q	1.000
20:43458059:T:C	L9P	1.000
20:43458109:G:C	G26R	1.000
20:43458110:G:A	G26D	1.000
20:43458110:G:T	G26V	1.000
20:43458131:T:C	L33P	1.000
20:43458133:A:G	K34E	1.000
20:43458134:A:C	K34T	1.000
20:43458134:A:T	K34I	1.000
20:43458135:A:C	K34N	1.000
20:43458135:A:T	K34N	1.000
20:43458139:G:T	G36W	1.000
20:43458140:G:A	G36E	1.000
20:43458362:T:C	Y37H	1.000
20:43458362:T:G	Y37D	1.000
20:43458365:G:C	G38R	1.000
20:43458366:G:A	G38D	1.000
20:43458368:T:A	F39I	1.000
20:43458368:T:C	F39L	1.000
20:43458368:T:G	F39V	1.000
20:43458369:T:C	F39S	1.000
20:43458369:T:G	F39C	1.000
20:43458370:C:A	F39L	1.000

dbSNP variants (sampled 300 via entrez): RS1000085717 (20:43463716 A>G), RS1000471190 (20:43458550 T>TGGGGGC), RS1000484137 (20:43457892 C>A,G,T), RS1000495369 (20:43462034 T>C), RS1000601922 (20:43456966 A>C), RS1001002035 (20:43460414 T>C), RS1001152301 (20:43464269 GATT>G), RS1001437410 (20:43459293 T>C), RS1001644992 (20:43457629 A>C,G), RS1001709099 (20:43457514 G>C), RS1002942801 (20:43457243 T>C), RS1003234011 (20:43461287 T>C), RS1003431910 (20:43461550 A>G), RS1003650234 (20:43463613 T>G), RS1004562739 (20:43461820 G>A)

Disease associations

OMIM: gene MIM:601944 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002804_2	Antibody level in response to infection	5.000000e-08
GCST003518_11	Daytime sleep phenotypes	5.000000e-06
GCST010988_325	Adult body size	5.000000e-10
GCST011743_67	HDL cholesterol levels in HIV infection	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007034	seropositivity measurement
EFO:0007035	Chlamydia pneumoniae seropositivity
EFO:0007828	daytime rest measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169149 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,273 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1095777	INDACATEROL	4	2,735
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 6 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.80	IC50	160	nM	MOLIBRESIB
5.22	Kd	5983	nM	CHEMBL3752910
5.22	ED50	5983	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 11 total; 2 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178468: Inhibition of SFRS6 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1600	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149493: Binding affinity to human SRSF6 incubated for 45 mins by Kinobead based pull down assay	kd	5.9833	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment	4
Cadmium Chloride	decreases expression, increases methylation	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	decreases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chloropicrin	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
GSK690693	affects cotreatment, decreases phosphorylation	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
((5Z)5-(1,3-benzodioxol-5-yl)methylene-2-phenylamino-3,5-dihydro-4H-imidazol-4-one)	decreases reaction, increases phosphorylation, decreases phosphorylation	1
bisphenol AF	increases 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
CHEMBL5105877	Binding	Inhibition of SRSF6 (unknown origin)	A critical update on the strategies towards small molecule inhibitors targeting Serine/arginine-rich (SR) proteins and Serine/arginine-rich proteins related kinases in alternative splicing. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6C1	SEES3-1V human SFRS6, clone1	Embryonic stem cell	Male
CVCL_A6C2	SEES3-1V human SFRS6, clone2	Embryonic stem cell	Male
CVCL_A6C3	SEES3-1V human SFRS6, clone3	Embryonic stem cell	Male
CVCL_B3I9	Abcam HEK293T SRSF6 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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