SRPK3

Summary

SRPK3 (SRSF protein kinase 3, HGNC:11402) is a protein-coding gene on chromosome Xq28, encoding SRSF protein kinase 3 (Q9UPE1). Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains.

This gene encodes a protein kinase similar to a protein kinase which is specific for the SR (serine/arginine-rich domain) family of splicing factors. A highly similar protein has been shown to play a role in muscle development in mice. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26576 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, X-linked 114 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 171 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11402
Approved symbol	SRPK3
Name	SRSF protein kinase 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	MSSK1
Ensembl gene	ENSG00000184343
Ensembl biotype	protein_coding
OMIM	301002
Entrez	26576

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000370100, ENST00000370101, ENST00000370104, ENST00000370108, ENST00000393786, ENST00000430541, ENST00000458681, ENST00000903807, ENST00000958764, ENST00000958765, ENST00000958766, ENST00000958767, ENST00000958768, ENST00000958769

RefSeq mRNA: 3 — MANE Select: NM_014370 NM_001170760, NM_001170761, NM_014370

CCDS: CCDS35441, CCDS55537, CCDS55538

Canonical transcript exons

ENST00000370101 — 15 exons

Exon	Start	End
ENSE00001294061	153781743	153781830
ENSE00001298443	153782121	153782208
ENSE00001299806	153782953	153783118
ENSE00001300982	153785081	153785173
ENSE00001303204	153781216	153781346
ENSE00001305763	153781505	153781613
ENSE00001315500	153781041	153781145
ENSE00001319774	153784294	153784394
ENSE00001324390	153783226	153783251
ENSE00001324583	153782772	153782878
ENSE00001330342	153784934	153785003
ENSE00001451787	153783752	153783884
ENSE00001451821	153783974	153784213
ENSE00001720776	153784750	153784857
ENSE00001895379	153785336	153785730

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 97.47.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8132 / max 87.0745, expressed in 206 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198103	0.7731	194
209875	0.0401	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.47	gold quality
gluteal muscle	UBERON:0002000	96.32	gold quality
gastrocnemius	UBERON:0001388	95.61	gold quality
triceps brachii	UBERON:0001509	95.60	gold quality
apex of heart	UBERON:0002098	95.25	gold quality
muscle of leg	UBERON:0001383	94.84	gold quality
muscle organ	UBERON:0001630	94.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.57	gold quality
vastus lateralis	UBERON:0001379	94.49	gold quality
quadriceps femoris	UBERON:0001377	94.40	gold quality
right atrium auricular region	UBERON:0006631	94.07	gold quality
skeletal muscle tissue	UBERON:0001134	93.92	gold quality
cardiac atrium	UBERON:0002081	93.08	gold quality
biceps brachii	UBERON:0001507	92.89	gold quality
heart left ventricle	UBERON:0002084	92.87	gold quality
cardiac ventricle	UBERON:0002082	92.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.98	gold quality
deltoid	UBERON:0001476	91.81	gold quality
tibialis anterior	UBERON:0001385	91.20	silver quality
muscle tissue	UBERON:0002385	91.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.08	gold quality
diaphragm	UBERON:0001103	91.04	silver quality
body of tongue	UBERON:0011876	90.98	gold quality
heart	UBERON:0000948	90.47	gold quality
cerebellar hemisphere	UBERON:0002245	90.09	gold quality
cerebellar cortex	UBERON:0002129	89.68	gold quality
mucosa of stomach	UBERON:0001199	88.13	gold quality
cerebellum	UBERON:0002037	87.00	gold quality
ascending aorta	UBERON:0001496	86.38	gold quality
thoracic aorta	UBERON:0001515	86.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	3.92
E-ANND-3	no	1.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting SRPK3, 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-MIR-3658	99.96	73.87	4379
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-3622A-5P	97.43	67.11	356
HSA-MIR-564	95.85	65.01	163

Literature-anchored findings (GeneRIF, showing 2)

• Alternative splicing of the alpha-exon of MEF2C regulates myogenesis. Loss of SRPK3 in rhabdomyosarcoma cells inhibits this splicing and blocks differentiation. (PMID:25404735)
• SRPK3 expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	srpk3	ENSDARG00000005916
mus_musculus	Srpk3	ENSMUSG00000002007
rattus_norvegicus	Srpk3	ENSRNOG00000054548
drosophila_melanogaster	nmo	FBGN0011817
drosophila_melanogaster	CG8565	FBGN0030697
drosophila_melanogaster	SRPK	FBGN0286813
caenorhabditis_elegans		WBGENE00002187
caenorhabditis_elegans		WBGENE00002188
caenorhabditis_elegans		WBGENE00003048
caenorhabditis_elegans		WBGENE00004055
caenorhabditis_elegans		WBGENE00004056
caenorhabditis_elegans		WBGENE00004980
caenorhabditis_elegans	gskl-2	WBGENE00007977
caenorhabditis_elegans	Y106G6E.1	WBGENE00013705

Paralogs (19): MAPK9 (ENSG00000050748), MAPK6 (ENSG00000069956), MOK (ENSG00000080823), NLK (ENSG00000087095), SRPK1 (ENSG00000096063), MAPK1 (ENSG00000100030), MAPK3 (ENSG00000102882), MAPK8 (ENSG00000107643), MAPK10 (ENSG00000109339), MAK (ENSG00000111837), MAPK14 (ENSG00000112062), CILK1 (ENSG00000112144), SRPK2 (ENSG00000135250), MAPK4 (ENSG00000141639), MAPK13 (ENSG00000156711), MAPK7 (ENSG00000166484), MAPK15 (ENSG00000181085), MAPK11 (ENSG00000185386), MAPK12 (ENSG00000188130)

Protein

Protein identifiers

SRSF protein kinase 3 — Q9UPE1 (reviewed: Q9UPE1)

Alternative names: Muscle-specific serine kinase 1, Serine/arginine-rich protein-specific kinase 3, Serine/threonine-protein kinase 23

All UniProt accessions (5): A8MPP7, A8MPY5, Q9UPE1, H7C1T4, H7C2I2

UniProt curated annotations — full annotation on UniProt →

Function. Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains. Phosphorylates the SR splicing factor SRSF1 and the lamin-B receptor (LBR) in vitro. Required for normal muscle development.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in skeletal and heart muscle. Also expressed in the fetal brain.

Disease relevance. Intellectual developmental disorder, X-linked 114 (XLID114) [MIM:301134] A disorder characterized by mild to severe intellectual disability, developmental delay, agenesis of the corpus callosum, abnormal eye movement, and ataxia. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UPE1-1	1	yes
Q9UPE1-2	2
Q9UPE1-3	3
Q9UPE1-4	4

RefSeq proteins (3): NP_001164231, NP_001164232, NP_055185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051334

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (25 total): sequence variant 7, compositionally biased region 5, splice variant 3, region of interest 3, binding site 2, modified residue 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPE1-F1	80.61	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 212 (proton acceptor)

Ligand- & substrate-binding residues (2): 85–93; 108

Post-translational modifications (2): 50, 330

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (8): spliceosomal complex assembly (GO:0000245), skeletal muscle tissue development (GO:0007519), cell differentiation (GO:0030154), intracellular signal transduction (GO:0035556), regulation of mRNA processing (GO:0050684), muscle tissue development (GO:0060537), protein phosphorylation (GO:0006468), muscle organ development (GO:0007517)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
striated muscle tissue development	1
skeletal muscle organ development	1
cellular developmental process	1
signal transduction	1
mRNA processing	1
regulation of mRNA metabolic process	1
tissue development	1
phosphorylation	1
protein modification process	1
animal organ development	1
muscle structure development	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRPK3	SBK2	P0C263	406
SRPK3	OR1L6	Q8NGR2	400
SRPK3	SRSF6	Q13247	390
SRPK3	PDZD4	Q76G19	370
SRPK3	STKLD1	Q8NE28	365
SRPK3	SRSF1	Q07955	358
SRPK3	METTL25B	Q96FB5	355
SRPK3	SRSF5	Q13243	351
SRPK3	CCNQ	Q8N1B3	339
SRPK3	IDH3G	P51553	332
SRPK3	SRSF4	Q08170	319
SRPK3	CIMAP1D	Q3SX64	318
SRPK3	SSR4	P51571	313
SRPK3	PABIR2	Q7Z309	313
SRPK3	SRSF3	P23152	312

IntAct

21 interactions, top by confidence:

A	B	Type	Score
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
SRPK1	SRPK3	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
SRPK3	rep	psi-mi:“MI:0915”(physical association)	0.550
YWHAE	SRPK3	psi-mi:“MI:0915”(physical association)	0.400
SFN	SRPK3	psi-mi:“MI:0915”(physical association)	0.400
SRPK3	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
rep	URB1	psi-mi:“MI:0914”(association)	0.350
CLK2	PRPF4	psi-mi:“MI:0914”(association)	0.350
CDK7	ACACB	psi-mi:“MI:0914”(association)	0.350
SRPK3	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
RIPOR3	AIP	psi-mi:“MI:0914”(association)	0.350
SRPK3	NVL	psi-mi:“MI:0914”(association)	0.350
SRPK1	HNRNPC	psi-mi:“MI:0914”(association)	0.350
SRPK3	NOP56	psi-mi:“MI:0914”(association)	0.350
Srek1	DDX3X	psi-mi:“MI:0914”(association)	0.350

BioGRID (232): SRPK3 (Co-fractionation), SRPK3 (Biochemical Activity), SRPK3 (Affinity Capture-MS), KIAA0020 (Affinity Capture-MS), GLYR1 (Affinity Capture-MS), RPF2 (Affinity Capture-MS), CACTIN (Affinity Capture-MS), RBM23 (Affinity Capture-MS), RSL1D1 (Affinity Capture-MS), RPL26 (Affinity Capture-MS), DDX31 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), WDR36 (Affinity Capture-MS), SON (Affinity Capture-MS), DDX27 (Affinity Capture-MS)

ESM2 similar proteins: A5PKJ4, B1AK53, B8Y466, D3ZG83, O14976, O54967, O60307, O70405, O75385, O96013, P0C865, P80192, P97756, Q02779, Q13164, Q17R13, Q2YDU3, Q3U1V8, Q3U214, Q3U2S4, Q3ULB5, Q3V016, Q4KMP7, Q4V793, Q5I1X5, Q5R8Z4, Q5TCX8, Q5U2X5, Q66HA1, Q66L42, Q6NZR5, Q6ZRS2, Q80XI6, Q80Y86, Q8BHL3, Q8BTW9, Q8C078, Q8CIP4, Q8N5S9, Q8TD08

Diamond homologs: B0Y8Y4, B8Y466, O54781, O70551, P78362, Q03563, Q45FA5, Q4WW94, Q5RD27, Q5UQ24, Q61IS6, Q93VK0, Q96SB4, Q9UPE1, Q9Z0G2, A0A509AHB6, A8WJR8, B2MVY4, E2RTQ7, G5EBT1, G5EDB2, O35492, O35493, O43781, O59853, O76039, O93982, P11802, P14680, P14681, P30285, P32350, P35426, P36616, P46551, P49657, P49761, P51137, P51566, P51568

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Viral Infection Pathways	5	9.6×	8e-03
Infectious disease	5	7.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	121
Likely benign	11
Benign	5

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3341103	NM_014370.4(SRPK3):c.203_204del (p.Pro68fs)	Pathogenic
3370404	NM_014370.4(SRPK3):c.475C>G (p.His159Asp)	Pathogenic
3370405	NM_014370.4(SRPK3):c.1373C>A (p.Thr458Asn)	Pathogenic
3600675	NM_014370.4(SRPK3):c.1014del (p.Gly340fs)	Likely pathogenic
4849372	NM_014370.4(SRPK3):c.211del (p.Ile71fs)	Likely pathogenic

SpliceAI

2021 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153781322:G:GT	donor_gain	1.0000
X:153781343:AAGGG:A	donor_loss	1.0000
X:153781344:AGGGT:A	donor_loss	1.0000
X:153781345:GG:G	donor_gain	1.0000
X:153781345:GGGTG:G	donor_loss	1.0000
X:153781346:GG:G	donor_gain	1.0000
X:153781346:GGTGA:G	donor_loss	1.0000
X:153781347:G:GG	donor_gain	1.0000
X:153781347:GTG:G	donor_loss	1.0000
X:153781614:G:GG	donor_gain	1.0000
X:153781829:GT:G	donor_gain	1.0000
X:153782765:A:AG	acceptor_gain	1.0000
X:153782766:G:GG	acceptor_gain	1.0000
X:153782875:GCAG:G	donor_gain	1.0000
X:153782878:GGT:G	donor_loss	1.0000
X:153782879:G:GG	donor_gain	1.0000
X:153782879:GT:G	donor_loss	1.0000
X:153782880:T:A	donor_loss	1.0000
X:153783075:G:GT	donor_gain	1.0000
X:153783878:GC:G	donor_gain	1.0000
X:153783883:GG:G	donor_gain	1.0000
X:153783884:GG:G	donor_gain	1.0000
X:153784292:A:AG	acceptor_gain	1.0000
X:153784293:G:GA	acceptor_gain	1.0000
X:153784293:GC:G	acceptor_gain	1.0000
X:153784293:GCAC:G	acceptor_gain	1.0000
X:153784293:GCACC:G	acceptor_gain	1.0000
X:153784348:A:G	donor_gain	1.0000
X:153784390:GGGTG:G	donor_gain	1.0000
X:153784391:GGTGG:G	donor_gain	1.0000

AlphaMissense

3695 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153781582:T:A	F90I	1.000
X:153781582:T:C	F90L	1.000
X:153781583:T:C	F90S	1.000
X:153781584:C:A	F90L	1.000
X:153781584:C:G	F90L	1.000
X:153781767:A:C	K108N	1.000
X:153781767:A:T	K108N	1.000
X:153782957:T:C	L196P	1.000
X:153782966:T:C	L199P	1.000
X:153782975:T:A	L202H	1.000
X:153782975:T:C	L202P	1.000
X:153782988:C:G	C206W	1.000
X:153782999:A:G	H210R	1.000
X:153783004:G:A	D212N	1.000
X:153783004:G:C	D212H	1.000
X:153783004:G:T	D212Y	1.000
X:153783005:A:C	D212A	1.000
X:153783005:A:G	D212G	1.000
X:153783005:A:T	D212V	1.000
X:153783006:C:A	D212E	1.000
X:153783006:C:G	D212E	1.000
X:153783010:A:G	K214E	1.000
X:153783012:G:C	K214N	1.000
X:153783012:G:T	K214N	1.000
X:153783013:C:T	P215S	1.000
X:153783014:C:A	P215H	1.000
X:153783014:C:G	P215R	1.000
X:153783019:A:C	N217H	1.000
X:153783019:A:G	N217D	1.000
X:153783020:A:C	N217T	1.000

dbSNP variants (sampled 300 via entrez): RS1000061564 (X:153786012 G>A), RS1000114958 (X:153785760 G>A,T), RS1001521011 (X:153779417 T>G), RS1001671484 (X:153784829 C>G,T), RS1001805336 (X:153784620 C>G,T), RS1003478178 (X:153783405 G>A,C), RS1004968259 (X:153779454 G>A), RS1005151024 (X:153785103 G>A,C,T), RS1005813893 (X:153782553 A>G), RS1006197209 (X:153782266 G>A), RS1007475287 (X:153781084 G>A), RS1007902224 (X:153781272 C>G,T), RS1008194515 (X:153784475 C>A,T), RS1009183132 (X:153780253 C>T), RS1009768135 (X:153780560 G>A)

Disease associations

OMIM: gene MIM:301002 | disease phenotypes: MIM:115200, MIM:117000, MIM:301134, MIM:608807

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, X-linked 114	Strong	X-linked
intellectual disability	Limited	X-linked

Mondo (7): familial dilated cardiomyopathy (MONDO:0016333), neurodevelopmental disorder (MONDO:0700092), multiminicore myopathy (MONDO:0018948), congenital myopathy (MONDO:0019952), intellectual developmental disorder, X-linked 114 (MONDO:0975828), autosomal recessive limb-girdle muscular dystrophy type 2J (MONDO:0012127), intellectual disability (MONDO:0001071)

Orphanet (4): Familial dilated cardiomyopathy (Orphanet:217607), Multiminicore myopathy (Orphanet:598), Congenital myopathy (Orphanet:97245), Titin-related limb-girdle muscular dystrophy R10 (Orphanet:140922)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000256	Macrocephaly
HP:0000486	Strabismus
HP:0000712	Emotional lability
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum
HP:0001338	Partial agenesis of the corpus callosum
HP:0001344	Absent speech
HP:0001417	X-linked inheritance
HP:0002280	Enlarged cisterna magna
HP:0002321	Vertigo
HP:0002342	Moderate intellectual disability
HP:0002451	Limb dystonia
HP:0003593	Infantile onset
HP:0003701	Proximal muscle weakness
HP:0006889	Borderline intellectual disability
HP:0006956	Lateral ventricle dilatation
HP:0010864	Severe intellectual disability
HP:0011220	Prominent forehead
HP:0011462	Young adult onset
HP:0030048	Colpocephaly
HP:0034198	Second trimester onset
HP:0034295	Reduced cerebral white matter volume

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C563854	Muscular Dystrophy, Limb-Girdle, Type 2J (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5415 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 272,978 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — SRPK family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 25 [PMID: 17935989]	Inhibition	5.76	pKi

ChEMBL bioactivities

49 potent at pChembl≥5 of 49 total, top 44 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.23	IC50	0.59	nM	CHEMBL5085558
9.22	IC50	0.6	nM	CHEMBL5085558
8.32	IC50	4.81	nM	CHEMBL4468747
7.92	Kd	12	nM	NINTEDANIB
7.89	Kd	13	nM	LESTAURTINIB
7.70	IC50	20	nM	CHEMBL5085558
7.70	EC50	20	nM	CHEMBL5085558
7.57	IC50	27	nM	CHEMBL4064277
7.40	IC50	40	nM	CHEMBL5085558
7.40	EC50	40	nM	CHEMBL5085558
7.23	Kd	59	nM	SUNITINIB
7.14	Kd	73	nM	STAUROSPORINE
7.10	Kd	80	nM	MIDOSTAURIN
6.92	Kd	120	nM	SU-014813
6.80	IC50	158.5	nM	CHEMBL4077195
6.78	IC50	166	nM	CHEMBL5074274
6.77	Kd	170	nM	FEDRATINIB
6.70	Kd	200	nM	KW-2449
6.62	Kd	240	nM	TOZASERTIB
6.60	Kd	250	nM	DOVITINIB
6.40	EC50	398	nM	CHEMBL4064277
6.40	Kd	400	nM	R-406
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.82	Kd	1500	nM	CHEMBL379218
5.80	IC50	1580	nM	STAUROSPORINE
5.80	Kd	1600	nM	PHA-665752
5.80	Kd	1600	nM	RUBOXISTAURIN
5.71	IC50	1960	nM	STAUROSPORINE
5.69	IC50	2050	nM	STAUROSPORINE
5.64	Kd	2300	nM	AXITINIB
5.54	Kd	2900	nM	TAE-684
5.48	Kd	3300	nM	RUXOLITINIB
5.46	IC50	3500	nM	CHEMBL5085599
5.46	Kd	3500	nM	CGP-52421
5.41	Kd	3900	nM	BOSUTINIB
5.22	Kd	6000	nM	CHEMBL1908395
5.21	EC50	6149	nM	CHEMBL5074274
5.12	Kd	7600	nM	GSK-461364
5.09	Kd	8200	nM	CRIZOTINIB
5.08	Kd	8300	nM	ERLOTINIB
5.03	Kd	9300	nM	TG100-115
5.00	IC50	9962	nM	CHEMBL5085599

PubChem BioAssay actives

39 with measured affinity, of 624 total; 29 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
N-[3-[[[2-(5-chloro-4-fluoro-1H-benzimidazol-2-yl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]-N-methylmethanesulfonamide	1969002: Inhibition of human SRPK3 using GRSRSRSRSR as substrate in presence of [gamma-33p]-ATP by radiometric hotspot kinase	ic50	0.0006	uM
3-(3-cyano-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazol-8-yl)benzenesulfonyl fluoride	1969002: Inhibition of human SRPK3 using GRSRSRSRSR as substrate in presence of [gamma-33p]-ATP by radiometric hotspot kinase	ic50	0.0048	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625078: Binding constant for SRPK3 kinase domain	kd	0.0120	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508093: Binding affinity to SRPK3	kd	0.0130	uM
N-[2-piperidin-1-yl-5-(trifluoromethyl)phenyl]pyridine-4-carboxamide	1969002: Inhibition of human SRPK3 using GRSRSRSRSR as substrate in presence of [gamma-33p]-ATP by radiometric hotspot kinase	ic50	0.0270	uM
Sunitinib	508093: Binding affinity to SRPK3	kd	0.0590	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	625078: Binding constant for SRPK3 kinase domain	kd	0.0730	uM
Midostaurin	508093: Binding affinity to SRPK3	kd	0.0800	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625078: Binding constant for SRPK3 kinase domain	kd	0.1200	uM
2-[(4-fluorophenyl)methoxy]-N-pyridin-3-yl-5-(trifluoromethyl)benzamide	1489176: Inhibition of human MSSK1 GRSRSRSRSR as substrate in presence of [gamma-33P]-ATP	ic50	0.1585	uM
5-pyridin-4-yl-N-[2-[4-(pyridin-2-ylmethyl)piperazin-1-yl]-5-(trifluoromethyl)phenyl]furan-2-carboxamide	1969002: Inhibition of human SRPK3 using GRSRSRSRSR as substrate in presence of [gamma-33p]-ATP by radiometric hotspot kinase	ic50	0.1660	uM
Fedratinib	625078: Binding constant for SRPK3 kinase domain	kd	0.1700	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625078: Binding constant for SRPK3 kinase domain	kd	0.2000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625078: Binding constant for SRPK3 kinase domain	kd	0.2400	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625078: Binding constant for SRPK3 kinase domain	kd	0.2500	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625078: Binding constant for SRPK3 kinase domain	kd	0.4000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625078: Binding constant for SRPK3 kinase domain	kd	1.5000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625078: Binding constant for SRPK3 kinase domain	kd	1.6000	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	625078: Binding constant for SRPK3 kinase domain	kd	1.6000	uM
Axitinib	625078: Binding constant for SRPK3 kinase domain	kd	2.3000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625078: Binding constant for SRPK3 kinase domain	kd	2.9000	uM
Ruxolitinib	625078: Binding constant for SRPK3 kinase domain	kd	3.3000	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide	508093: Binding affinity to SRPK3	kd	3.5000	uM
Bosutinib	625078: Binding constant for SRPK3 kinase domain	kd	3.9000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625078: Binding constant for SRPK3 kinase domain	kd	6.0000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	625078: Binding constant for SRPK3 kinase domain	kd	7.6000	uM
Crizotinib	625078: Binding constant for SRPK3 kinase domain	kd	8.2000	uM
Erlotinib	625078: Binding constant for SRPK3 kinase domain	kd	8.3000	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	625078: Binding constant for SRPK3 kinase domain	kd	9.3000	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
aristolochic acid I	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Gold Compounds	increases expression	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

229 unique, capped per target: 229 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017925	Binding	Inhibition of SRPK3 assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ49	HAP1 SRPK3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01798992	PHASE4	COMPLETED	Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02033278	PHASE2	TERMINATED	Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic