SRSF5

Summary

SRSF5 (serine and arginine rich splicing factor 5, HGNC:10787) is a protein-coding gene on chromosome 14q24, encoding Serine/arginine-rich splicing factor 5 (Q13243). Plays a role in constitutive splicing and can modulate the selection of alternative splice sites.

The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6430 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_001320214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10787
Approved symbol	SRSF5
Name	serine and arginine rich splicing factor 5
Location	14q24
Locus type	gene with protein product
Status	Approved
Aliases	SRP40, HRS
Ensembl gene	ENSG00000100650
Ensembl biotype	protein_coding
OMIM	600914
Entrez	6430

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 42 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000394366, ENST00000553369, ENST00000553521, ENST00000553548, ENST00000553635, ENST00000554021, ENST00000554465, ENST00000554929, ENST00000555349, ENST00000555412, ENST00000555547, ENST00000556184, ENST00000556330, ENST00000556436, ENST00000556587, ENST00000556647, ENST00000557154, ENST00000557435, ENST00000557460, ENST00000880757, ENST00000880758, ENST00000880759, ENST00000880760, ENST00000880761, ENST00000880762, ENST00000880763, ENST00000880764, ENST00000880765, ENST00000880766, ENST00000880767, ENST00000921621, ENST00000921622, ENST00000921623, ENST00000921624, ENST00000921625, ENST00000921626, ENST00000921627, ENST00000921628, ENST00000921629, ENST00000921630, ENST00000921631, ENST00000921632, ENST00000921633, ENST00000921634, ENST00000921635, ENST00000921636, ENST00000921637, ENST00000921638, ENST00000921640, ENST00000921641, ENST00000960938, ENST00000960939, ENST00000960940

RefSeq mRNA: 4 — MANE Select: NM_001320214 NM_001039465, NM_001320214, NM_001411040, NM_006925

CCDS: CCDS32109, CCDS91892

Canonical transcript exons

ENST00000557154 — 8 exons

Exon	Start	End
ENSE00002431486	69771194	69772005
ENSE00002448230	69767142	69767255
ENSE00003567548	69770467	69770540
ENSE00003581675	69769182	69769251
ENSE00003596298	69770995	69771105
ENSE00003615889	69768138	69768282
ENSE00003626590	69768604	69768674
ENSE00003661344	69768798	69768896

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 359.7925 / max 7277.2824, expressed in 1828 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140365	329.8717	1827
140367	5.0589	1242
140364	4.1879	1452
140378	4.0085	1321
140376	3.3306	1080
140374	2.6483	978
140372	2.0204	866
140377	1.8843	752
140366	1.7571	729
140375	0.9146	505

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.67	gold quality
adenohypophysis	UBERON:0002196	99.65	gold quality
left lobe of thyroid gland	UBERON:0001120	99.61	gold quality
pituitary gland	UBERON:0000007	99.60	gold quality
left ovary	UBERON:0002119	99.60	gold quality
right lobe of thyroid gland	UBERON:0001119	99.59	gold quality
mucosa of stomach	UBERON:0001199	99.58	gold quality
cerebellar hemisphere	UBERON:0002245	99.57	gold quality
calcaneal tendon	UBERON:0003701	99.57	gold quality
granulocyte	CL:0000094	99.55	gold quality
thyroid gland	UBERON:0002046	99.55	gold quality
right ovary	UBERON:0002118	99.54	gold quality
right lung	UBERON:0002167	99.53	gold quality
tibial nerve	UBERON:0001323	99.52	gold quality
body of uterus	UBERON:0009853	99.52	gold quality
skin of abdomen	UBERON:0001416	99.51	gold quality
skin of leg	UBERON:0001511	99.51	gold quality
cerebellar cortex	UBERON:0002129	99.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.51	gold quality
lower esophagus mucosa	UBERON:0035834	99.51	gold quality
monocyte	CL:0000576	99.49	gold quality
left uterine tube	UBERON:0001303	99.49	gold quality
metanephros cortex	UBERON:0010533	99.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.49	gold quality
mononuclear cell	CL:0000842	99.48	gold quality
lower esophagus	UBERON:0013473	99.48	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.48	gold quality
endocervix	UBERON:0000458	99.45	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	686.74
E-CURD-122	yes	42.55
E-CURD-88	yes	26.77
E-CURD-112	yes	5.25
E-CURD-89	no	1961.10
E-MTAB-7303	no	341.90
E-HCAD-6	no	34.62
E-HCAD-4	no	34.52
E-GEOD-125970	no	8.43
E-HCAD-1	no	7.08
E-HCAD-31	no	4.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting SRSF5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-9898	99.00	67.89	500

Literature-anchored findings (GeneRIF, showing 22)

• role in c-H-ras alternative splicing regulation (PMID:12665590)
• SR proteins 9G8, SC35, ASF/SF2, and SRp40 have effects on the utilization of the A1 to A5 splicing sites of HIV-1 RNA (PMID:15123677)
• activates the ESE (exon splicing enhancer) which regulates HIV-1 rev, env, vpu, and nef gene expression (PMID:15163745)
• SRp40 regulates the switch in splicing from production of CREMtau(2)alpha to CREMalpha (PMID:16103121)
• SC35, SRp40, and heterogeneous nuclear ribonucleoprotein A1 interact competitively at the HIV-1 Tat exon 2 splicing site (PMID:16990281)
• SRp40 antagonizes ASF/SF2 and SRp55 by competing for binding to certain sites in exon 5, thereby promoting TF exon 5 exclusion, an event unique to asTF biosynthesis. (PMID:19843576)
• 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)
• We show that changes in alternative splicing of hnRNP A/B, affected by up regulation of SRSF5 (SRp40) or by treatment with C6-ceramide, occur within supraspliceosomes. (PMID:22100336)
• Relative levels of SRp20, SRp30c, and SRp40 in TM cells control differential expression of the two alternatively spliced isoforms of the GR and thereby regulate GC responsiveness. (PMID:22205602)
• Suggest that SRp40 might be associated with GRalpha transcripts in systemic lupus erythematosus patients. (PMID:25665148)
• Enhanced SRSF5 Protein Expression Reinforces Lamin A mRNA Production in HeLa Cells and Fibroblasts of Progeria Patients (PMID:26670336)
• the up-regulated expression of SRSF 5-7 proteins in LC with much more profound up-regulation in SCLC than in NSCLC and suggest that up-regulation of the SRSFs is related to SCLC proliferation. Moreover, we identified SRSF5 as a novel detection marker for SCLC and pleural metastatic cancer cells. (PMID:27565915)
• Cold induction of serine and arginine rich splicing factor 5 (SRSF5) is independent of cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3). (PMID:28536481)
• Posttranslational modification of SR proteins underlies the regulation of their mRNA export activities and distinguishes pluripotent from differentiated cells. (PMID:28592444)
• this study demonstrates that HRS acts as a key component of TLR7 signaling to orchestrate immune and inflammatory responses during EV71 infection (PMID:28854257)
• we show that ErbB3 interacts with the ESCRT-0 subunit Hrs both in the presence and absence of heregulin. This indicates an ESCRT-mediated sorting of ErbB3 to late endosomes and lysosomes, and in line with this we show that impaired ESCRT function leads to an endosomal accumulation of ErbB3. (PMID:28867611)
• Study found that SRSF5 is a novel target of SRSF3. SRSF5 is overexpressed in oral squamous cell carcinoma (OSCC) and functions as an oncogene. Its downregulation in OSCC cell lines slows cell growth, cycle progression, and tumor growth. The expression of SRSF5 seems to controlled by an autoregulation mechanism. (PMID:29857020)
• In this study, we uncover an alternative role for the ESCRT-0 component hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) in promoting the constitutive recycling of transmembrane proteins. We find that endosomal localization of the actin nucleating factor Wiscott-Aldrich syndrome protein and SCAR homologue (WASH) requires HRS, which occupies adjacent endosomal subdomains (PMID:29891722)
• upon glucose intake, the splicing factor SRSF5 is specifically induced through Tip60-mediated acetylation on K125, which antagonizes Smurf1-mediated ubiquitylation. SRSF5 promotes the alternative splicing of CCAR1 to produce CCAR1S proteins, which promote tumor growth by enhancing glucose consumption and acetyl-CoA production. (PMID:29942010)
• Antitumor activity of SR splicing-factor 5 knockdown by downregulating pyruvate kinase M2 in non-small cell lung cancer cells. (PMID:31106485)
• Genes involved in glucocorticoid receptor signalling affect susceptibility to mood disorders. (PMID:32400287)
• CPEB2 m6A methylation regulates blood-tumor barrier permeability by regulating splicing factor SRSF5 stability. (PMID:36064747)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srsf5b	ENSDARG00000027734
mus_musculus	Srsf5	ENSMUSG00000021134
rattus_norvegicus	Srsf5	ENSRNOG00000005513

Paralogs (8): RSRC2 (ENSG00000111011), SRSF9 (ENSG00000111786), SRSF3 (ENSG00000112081), SRSF7 (ENSG00000115875), SRSF4 (ENSG00000116350), RSRP1 (ENSG00000117616), SRSF6 (ENSG00000124193), SRSF1 (ENSG00000136450)

Protein

Protein identifiers

Serine/arginine-rich splicing factor 5 — Q13243 (reviewed: Q13243)

Alternative names: Delayed-early protein HRS, Pre-mRNA-splicing factor SRP40, Splicing factor, arginine/serine-rich 5

All UniProt accessions (4): Q13243, B4DJK0, B4DUA4, G3V5K8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in constitutive splicing and can modulate the selection of alternative splice sites.

Subunit / interactions. Interacts (via RS domain) with PHF5A (via N-terminus). Found in a pre-mRNA splicing complex with SRSF4/SFRS4, SRSF5/SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2.

Subcellular location. Nucleus.

Post-translational modifications. Extensively phosphorylated on serine residues in the RS domain.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the splicing factor SR family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13243-1	SRP40-1	yes
Q13243-2	SRP40-2
Q13243-4	SRP40-3
Q13243-3	SRP40-4

RefSeq proteins (4): NP_001034554, NP_001307143, NP_001397969, NP_008856 (=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
IPR050374	RRT5_SRSF_SR	Family

Pfam: PF00076

UniProt features (19 total): modified residue 7, splice variant 3, compositionally biased region 3, domain 2, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13243-F1	63.90	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 (7): 227, 229, 233, 250, 253, 86, 167

Function

Pathways and Gene Ontology

Reactome pathways

12 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-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: 254 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, AAGCAAT_MIR137, WANG_CLIM2_TARGETS_UP, TGCGCANK_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_REGENERATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, ATGTTAA_MIR302C

GO Biological Process (10): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splice site recognition (GO:0006376), mRNA processing (GO:0006397), cellular response to insulin stimulus (GO:0032869), positive regulation of RNA splicing (GO:0033120), liver regeneration (GO:0097421), RNA splicing, via transesterification reactions (GO:0000375), liver development (GO:0001889), RNA splicing (GO:0008380), response to insulin (GO:0032868)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), protein kinase B binding (GO:0043422), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), 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
Transport of Mature Transcript to Cytoplasm	1
mRNA Splicing	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
RNA processing	2
RNA splicing	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
spliceosomal complex assembly	1
protein-RNA complex assembly	1
mRNA metabolic process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
positive regulation of gene expression	1
regulation of RNA splicing	1
liver development	1
animal organ regeneration	1
gland development	1
hepaticobiliary system development	1
response to peptide hormone	1
nucleic acid binding	1
RNA binding	1
protein kinase binding	1
intracellular membraneless organelle	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRSF5	HNRNPA1	P09651	896
SRSF5	HNRNPH1	P31943	881
SRSF5	U2AF1	Q01081	819
SRSF5	RSRC1	Q96IZ7	796
SRSF5	HIPK3	Q9H422	772
SRSF5	SRSF11	Q05519	770
SRSF5	SRPK1	Q96SB4	770
SRSF5	LUC7L	Q9NQ29	761
SRSF5	SLU7	O95391	693
SRSF5	LUC7L3	O95232	658
SRSF5	U2AF2	P26368	646
SRSF5	SNRNP70	P08621	643
SRSF5	RBM5	P52756	628
SRSF5	HNRNPL	P14866	587
SRSF5	RBMXL2	O75526	586

IntAct

192 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
SRSF5	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.690
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
SRSF5	ZRSR2	psi-mi:“MI:0915”(physical association)	0.560
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
SRSF5	CBX6	psi-mi:“MI:0914”(association)	0.530
PRPF38A	H2BC17	psi-mi:“MI:0914”(association)	0.510
ESR1		psi-mi:“MI:0914”(association)	0.460
SRSF5		psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
SF3A2	SRSF5	psi-mi:“MI:0915”(physical association)	0.400
PAK1	SRSF5	psi-mi:“MI:0915”(physical association)	0.370
SRSF5	CCR2	psi-mi:“MI:0915”(physical association)	0.370
SRSF5	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
RPS6KA1	SRSF5	psi-mi:“MI:0915”(physical association)	0.370
SNRPF	SRSF5	psi-mi:“MI:0915”(physical association)	0.370
Tsc2	SRSF5	psi-mi:“MI:0914”(association)	0.350
FLII	TUBG1	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
SF1	U2SURP	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
DDX41	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (558): SRSF5 (Affinity Capture-MS), SRSF5 (Affinity Capture-MS), SRSF5 (Affinity Capture-MS), NCL (Co-fractionation), SRRM2 (Co-fractionation), SRSF5 (Co-fractionation), SRSF5 (Co-fractionation), TRA2B (Co-fractionation), SRSF5 (Affinity Capture-MS), SRSF5 (Affinity Capture-MS), SRSF5 (Affinity Capture-MS), SRSF5 (Biochemical Activity), SRSF5 (Affinity Capture-MS), SRSF5 (Affinity Capture-MS), SRSF5 (Affinity Capture-MS)

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

2 interactions.

A	Effect	B	Mechanism
SMURF1	“down-regulates quantity by destabilization”	SRSF5	ubiquitination
AKT2	“up-regulates activity”	SRSF5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 205 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
Eukaryotic Translation Initiation	9	19.8×	1e-08
Cap-dependent Translation Initiation	9	19.8×	1e-08
SARS-CoV-1 modulates host translation machinery	9	19.8×	1e-08
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	10	19.4×	2e-09
Peptide chain elongation	21	19.0×	2e-19
Viral mRNA Translation	21	19.0×	2e-19
Transport of Mature Transcript to Cytoplasm	7	19.0×	9e-07
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	21	18.8×	2e-19

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	9	29.6×	4e-09
positive regulation of transcription by RNA polymerase III	5	25.6×	1e-04
cytoplasmic translation	23	23.3×	2e-22
negative regulation of mRNA splicing, via spliceosome	5	20.9×	3e-04
positive regulation of viral genome replication	6	19.1×	7e-05
positive regulation of transcription by RNA polymerase I	5	17.7×	6e-04
ribosomal large subunit biogenesis	7	17.0×	2e-05
ribosomal small subunit biogenesis	11	13.7×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1324 predictions. Top by Δscore:

Variant	Effect	Δscore
14:69727151:G:GT	donor_gain	1.0000
14:69768133:A:AG	acceptor_gain	1.0000
14:69768136:A:AG	acceptor_gain	1.0000
14:69768137:G:GG	acceptor_gain	1.0000
14:69768137:G:T	acceptor_loss	1.0000
14:69768137:GGAA:G	acceptor_gain	1.0000
14:69768243:GA:G	donor_gain	1.0000
14:69768278:TTGTG:T	donor_gain	1.0000
14:69768279:TGTG:T	donor_gain	1.0000
14:69768280:GTG:G	donor_gain	1.0000
14:69768280:GTGG:G	donor_gain	1.0000
14:69768281:TG:T	donor_gain	1.0000
14:69768281:TGGT:T	donor_gain	1.0000
14:69768282:GG:G	donor_gain	1.0000
14:69768283:G:C	donor_loss	1.0000
14:69768283:G:GG	donor_gain	1.0000
14:69768284:T:A	donor_loss	1.0000
14:69768599:TTTAG:T	acceptor_loss	1.0000
14:69768601:TAG:T	acceptor_loss	1.0000
14:69768602:A:AC	acceptor_loss	1.0000
14:69768603:GGA:G	acceptor_gain	1.0000
14:69768672:AAGGT:A	donor_loss	1.0000
14:69768673:AGGT:A	donor_loss	1.0000
14:69768674:GGT:G	donor_loss	1.0000
14:69768675:G:A	donor_loss	1.0000
14:69768676:T:G	donor_loss	1.0000
14:69768794:GTAG:G	acceptor_loss	1.0000
14:69768795:TA:T	acceptor_loss	1.0000
14:69768796:A:AG	acceptor_gain	1.0000
14:69768796:AG:A	acceptor_gain	1.0000

AlphaMissense

1760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:69768175:T:C	F7L	1.000
14:69768176:T:C	F7S	1.000
14:69768176:T:G	F7C	1.000
14:69768177:C:A	F7L	1.000
14:69768177:C:G	F7L	1.000
14:69768179:T:A	I8N	1.000
14:69768182:G:A	G9E	1.000
14:69768238:G:A	G28R	1.000
14:69768238:G:C	G28R	1.000
14:69768239:G:A	G28E	1.000
14:69768239:G:T	G28V	1.000
14:69768264:A:C	K36N	1.000
14:69768264:A:T	K36N	1.000
14:69768271:T:C	F39L	1.000
14:69768272:T:C	F39S	1.000
14:69768273:T:A	F39L	1.000
14:69768273:T:G	F39L	1.000
14:69768274:G:C	G40R	1.000
14:69768275:G:A	G40D	1.000
14:69768277:T:C	F41L	1.000
14:69768278:T:C	F41S	1.000
14:69768278:T:G	F41C	1.000
14:69768279:T:A	F41L	1.000
14:69768279:T:G	F41L	1.000
14:69768281:T:A	V42E	1.000
14:69768607:T:C	F44L	1.000
14:69768608:T:C	F44S	1.000
14:69768608:T:G	F44C	1.000
14:69768609:T:A	F44L	1.000
14:69768609:T:G	F44L	1.000

dbSNP variants (sampled 300 via entrez): RS1000041250 (14:69771646 T>C), RS1000320344 (14:69767144 C>T), RS1000487319 (14:69770275 A>G), RS1001042489 (14:69770590 C>T), RS1001300670 (14:69767733 C>T), RS1001349938 (14:69768448 T>C), RS1001493919 (14:69768881 C>G,T), RS1002415015 (14:69767381 G>A,C,T), RS1002532765 (14:69767833 C>T), RS1003046208 (14:69767977 T>A), RS1003602798 (14:69771954 C>T), RS1003610562 (14:69771396 G>A,C), RS1004502618 (14:69767340 C>G,T), RS1004611411 (14:69770880 A>C,T), RS1004995425 (14:69766285 T>C)

Disease associations

OMIM: gene MIM:600914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002397_365	Mean spheric corpuscular volume	2.000000e-09
GCST90002403_513	Red blood cell count	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, affects splicing, affects cotreatment, increases expression, decreases expression	4
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
bisphenol A	affects expression, decreases expression, affects cotreatment	3
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance, affects splicing	3
Benzo(a)pyrene	decreases expression	3
nickel chloride	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	affects cotreatment, affects expression, increases abundance	2
Ozone	affects expression, increases abundance, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Dronabinol	increases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
resorcinol	increases expression	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3I8	Abcam HEK293T SRSF5 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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