SYMPK

Summary

SYMPK (symplekin scaffold protein, HGNC:22935) is a protein-coding gene on chromosome 19q13.32, encoding Symplekin (Q92797). Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3’-end processing. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

This gene encodes a nuclear protein that functions in the regulation of polyadenylation and promotes gene expression. The protein forms a high-molecular weight complex with components of the polyadenylation machinery. It is thought to serve as a scaffold for recruiting regulatory factors to the polyadenylation complex. It also participates in 3’-end maturation of histone mRNAs, which do not undergo polyadenylation. The protein also localizes to the cytoplasmic plaques of tight junctions in some cell types.

Source: NCBI Gene 8189 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 191 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_004819

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22935
Approved symbol	SYMPK
Name	symplekin scaffold protein
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	SYM, SPK, Pta1
Ensembl gene	ENSG00000125755
Ensembl biotype	protein_coding
OMIM	602388
Entrez	8189

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 28 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000245934, ENST00000593504, ENST00000593899, ENST00000593959, ENST00000594293, ENST00000596518, ENST00000596824, ENST00000598059, ENST00000598155, ENST00000598329, ENST00000598364, ENST00000598896, ENST00000599460, ENST00000599814, ENST00000600237, ENST00000601582, ENST00000601600, ENST00000602061, ENST00000715464, ENST00000876448, ENST00000876449, ENST00000876450, ENST00000876451, ENST00000876452, ENST00000876453, ENST00000876454, ENST00000876455, ENST00000876456, ENST00000876457, ENST00000876458, ENST00000876459, ENST00000876460, ENST00000876461, ENST00000876462, ENST00000876463, ENST00000876464, ENST00000876465, ENST00000876466, ENST00000916416

RefSeq mRNA: 1 — MANE Select: NM_004819 NM_004819

CCDS: CCDS12676

Canonical transcript exons

ENST00000245934 — 27 exons

Exon	Start	End
ENSE00001208477	45815410	45815697
ENSE00003478657	45815851	45816183
ENSE00003478849	45826226	45826373
ENSE00003487423	45823767	45823875
ENSE00003495246	45827510	45827623
ENSE00003523255	45831384	45831588
ENSE00003532476	45821384	45821485
ENSE00003568866	45816798	45816974
ENSE00003574349	45842250	45842489
ENSE00003589145	45854175	45854240
ENSE00003591991	45854391	45854507
ENSE00003607791	45847752	45848001
ENSE00003616859	45823372	45823472
ENSE00003619319	45816482	45816577
ENSE00003623691	45830054	45830204
ENSE00003626258	45852482	45852535
ENSE00003631597	45844030	45844200
ENSE00003632999	45838461	45838615
ENSE00003633835	45835078	45835228
ENSE00003651512	45822756	45822846
ENSE00003653666	45817959	45818146
ENSE00003662674	45852312	45852385
ENSE00003669485	45825171	45825331
ENSE00003720913	45828970	45829205
ENSE00003750549	45827837	45827918
ENSE00003790249	45848750	45848876
ENSE00004026841	45863058	45863147

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.5412 / max 183.5355, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181582	31.0085	1818
181583	0.5079	282
181580	0.0129	3
181579	0.0119	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.10	gold quality
right testis	UBERON:0004534	97.08	gold quality
adenohypophysis	UBERON:0002196	96.41	gold quality
stromal cell of endometrium	CL:0002255	95.94	gold quality
pituitary gland	UBERON:0000007	95.62	gold quality
lower esophagus mucosa	UBERON:0035834	95.22	gold quality
right uterine tube	UBERON:0001302	94.96	gold quality
granulocyte	CL:0000094	94.91	gold quality
mucosa of transverse colon	UBERON:0004991	94.83	gold quality
sural nerve	UBERON:0015488	94.73	gold quality
right lobe of thyroid gland	UBERON:0001119	94.67	gold quality
right lobe of liver	UBERON:0001114	94.43	gold quality
left lobe of thyroid gland	UBERON:0001120	94.42	gold quality
type B pancreatic cell	CL:0000169	94.38	gold quality
right frontal lobe	UBERON:0002810	94.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.28	gold quality
testis	UBERON:0000473	94.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.01	gold quality
skin of leg	UBERON:0001511	93.98	gold quality
ventricular zone	UBERON:0003053	93.95	gold quality
skin of abdomen	UBERON:0001416	93.87	gold quality
metanephros cortex	UBERON:0010533	93.83	gold quality
spleen	UBERON:0002106	93.81	gold quality
male germ cell	CL:0000015	93.80	gold quality
sperm	CL:0000019	93.79	gold quality
cerebellar hemisphere	UBERON:0002245	93.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.73	gold quality
body of stomach	UBERON:0001161	93.68	gold quality
body of uterus	UBERON:0009853	93.61	gold quality
endocervix	UBERON:0000458	93.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1

miRNA regulators (miRDB)

1 targeting SYMPK, 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-7856-5P	99.75	69.99	2901

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• symplekin has a role in HSF1 modulation of Hsp70 mRNA polyadenylation (PMID:14707147)
• In Xenopus, symplekin interacts with the CPSF complex and the regulatory protein CPEB, and is required for polyadenylation of CPE-containing RNA (PMID:15550246)
• The decreased expression of symplekin may be an early step in the transformation of hepatocytes, whereas alteration of the expression of adherens junctions and desmosomes may indicate more serious changes. (PMID:17880531)
• The symplekin/ZONAB complex inhibits intestinal cell differentiation by the repression of AML1/Runx1. (PMID:19328795)
• Data show that claudin-2 expression was reduced following symplekin down-regulation, and siRNA-mediated claudin-2 down-regulation increased the transepithelial resistance and decreased cyclin D1 expression and ZONAB nuclear localization. (PMID:20133805)
• Symplekin supports faithful mitosis by contributing to the formation of a bipolar spindle apparatus. Depletion of symplekin attenuates microtubule polymerization as well as expression of the critical microtubule polymerization protein CKAP5 (TOGp). (PMID:20823274)
• crystal structure at 2.4 A resolution of the amino-terminal domain (residues 30-340) of human symplekin in a ternary complex with the Pol II carboxy-terminal domain (CTD) Ser 5 phosphatase Ssu72 and a CTD Ser 5 phosphopeptide (PMID:20861839)
• Symplekin expression regulates the assembly of tight junctions, thus helps to maintain the integrity of the epithelial monolayer and cellular polarity. (PMID:22218735)
• Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA. (PMID:23994619)
• CPSF2 and SYMPK, are RBFOX2 cofactors for both inclusion and exclusion of internal exons. (PMID:25921069)
• Data indicate rs56848936 in the gene symplekin protein (SYMPK) at 19q13.3, associated with colon cancer risk. (PMID:28295283)
• The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting. (PMID:28630428)
• Results indicated that reductase becomes destabilized in the absence of UBIAD1, resulting in reduced cholesterol synthesis and intracellular accumulation. Findings further establish UBIAD1 as a central player in the reductase ERAD pathway and regulation of isoprenoid synthesis. (PMID:29167270)
• Research proved that high Rab11 expression enhances cellular multiplication and invasiveness of bladder cancer, possibly by regulating the NF-kappaB signaling pathway. (PMID:30032159)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sympk	ENSDARG00000059553
mus_musculus	Sympk	ENSMUSG00000023118
rattus_norvegicus	Sympk	ENSRNOG00000014353
drosophila_melanogaster	Sym	FBGN0037371
caenorhabditis_elegans		WBGENE00017797

Protein

Protein identifiers

Symplekin — Q92797 (reviewed: Q92797)

All UniProt accessions (8): Q92797, A0A087WUE9, M0QXP5, M0R033, M0R039, M0R180, M0R1C2, M0R3C7

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3’-end processing. Specific component of the tight junction (TJ) plaque, but might not be an exclusively junctional component. May have a house-keeping rule. Is involved in pre-mRNA polyadenylation. Enhances SSU72 phosphatase activity.

Subunit / interactions. Found in a heat-sensitive complex at least composed of several cleavage and polyadenylation specific and cleavage stimulation factors. Interacts with CPSF2, CPSF3 and CSTF2. Interacts (via N-terminus) with HSF1; this interaction is direct and occurs upon heat shock. Interacts with SSU72.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Tight junction. Cell membrane. Nucleus. Nucleoplasm.

Tissue specificity. In testis, expressed in polar epithelia and Sertoli cells but not in vascular endothelia. The protein is detected in stomach, duodenum, pancreas, liver, fetal brain, carcinomas, lens-forming cells, fibroblasts, lymphocytes, lymphoma cells, erythroleukemia cells but not in endothelium of vessels, epidermis, intercalated disks, Purkinje fiber cells of the heart and lymph node.

Domain organisation. The HEAT repeats have been determined based on 3D-structure analysis of the D.melanogaster ortholog and are not detected by sequence-based prediction programs.

Miscellaneous. Could be used as a differentiation marker in the differential diagnosis of tumors. 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 Symplekin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92797-1	1	yes
Q92797-2	2

RefSeq proteins (1): NP_004810* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021850	Symplekin/Pta1	Family
IPR022075	Symplekin_C	Domain
IPR032460	Symplekin/Pta1_N	Domain

Pfam: PF11935, PF12295

UniProt features (56 total): helix 25, modified residue 7, repeat 5, compositionally biased region 5, cross-link 4, region of interest 4, splice variant 2, chain 1, short sequence motif 1, mutagenesis site 1, strand 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3O2T	X-RAY DIFFRACTION	1.4
3ODS	X-RAY DIFFRACTION	1.9
4H3K	X-RAY DIFFRACTION	2
3ODR	X-RAY DIFFRACTION	2.2
4H3H	X-RAY DIFFRACTION	2.2
3O2Q	X-RAY DIFFRACTION	2.4
3O2S	X-RAY DIFFRACTION	2.5
9NH5	ELECTRON MICROSCOPY	2.82
9NH6	ELECTRON MICROSCOPY	2.82
9NGO	ELECTRON MICROSCOPY	3.01
9N96	ELECTRON MICROSCOPY	3.18
6V4X	ELECTRON MICROSCOPY	3.2
9NB1	ELECTRON MICROSCOPY	3.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92797-F1	75.47	0.39

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 (11): 13, 494, 1221, 1222, 1243, 1257, 1259, 361, 361, 483, 1239

Mutagenesis-validated functional residues (1):

Position	Phenotype
185	abolishes stimulation of ssu72 phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-159234	Transport of Mature mRNAs Derived from Intronless Transcripts
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-75067	Processing of Capped Intronless Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 167 (showing top): GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KEGG_TIGHT_JUNCTION, GGAMTNNNNNTCCY_UNKNOWN, COUP_01, WEI_MYCN_TARGETS_WITH_E_BOX, NFKB_C, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_BINDING, REACTOME_MRNA_3_END_PROCESSING, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, HNF4_DR1_Q3, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION

GO Biological Process (3): mRNA processing (GO:0006397), cell adhesion (GO:0007155), negative regulation of protein binding (GO:0032091)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), nuclear stress granule (GO:0097165), nucleus (GO:0005634), membrane (GO:0016020), nuclear body (GO:0016604), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-9 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	2
RNA processing	1
mRNA metabolic process	1
cellular process	1
protein binding	1
regulation of protein binding	1
negative regulation of binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
mRNA cleavage factor complex	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
nucleoplasm	1
cell junction	1

Protein interactions and networks

STRING

1974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYMPK	CPSF3	Q9UKF6	997
SYMPK	CSTF2	P33240	997
SYMPK	CPSF2	Q9P2I0	997
SYMPK	PAPOLA	P51003	978
SYMPK	PAPOLG	Q9BWT3	977
SYMPK	PAPOLB	Q9NRJ5	976
SYMPK	TENT2	Q6PIY7	974
SYMPK	CPSF1	Q10570	961
SYMPK	CPEB1	Q9BZB8	961
SYMPK	CSTF3	Q12996	960
SYMPK	PARN	O95453	938
SYMPK	WDR33	Q9C0J8	885
SYMPK	CSTF1	Q05048	871
SYMPK	LSM11	P83369	867
SYMPK	CPSF6	Q16630	866

IntAct

146 interactions, top by confidence:

A	B	Type	Score
CPSF2	SYMPK	psi-mi:“MI:0915”(physical association)	0.850
SYMPK	CPSF2	psi-mi:“MI:0914”(association)	0.850
CPSF2	SYMPK	psi-mi:“MI:0914”(association)	0.850
SYMPK	CPSF2	psi-mi:“MI:0915”(physical association)	0.850
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SYMPK	BSG	psi-mi:“MI:0915”(physical association)	0.670
CPSF3	CPSF4	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
CDC73	CSTF2	psi-mi:“MI:0914”(association)	0.580
SYMPK	SSU72	psi-mi:“MI:0407”(direct interaction)	0.560
SYMPK		psi-mi:“MI:0915”(physical association)	0.560
HTT	SYMPK	psi-mi:“MI:0915”(physical association)	0.560
CPSF1	CPSF4	psi-mi:“MI:0915”(physical association)	0.560
SYMPK	CPSF4	psi-mi:“MI:0914”(association)	0.530
TUT1	CSTF2	psi-mi:“MI:0914”(association)	0.530
WDR33	CPSF4	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530
CSTF2T	CRTAP	psi-mi:“MI:0914”(association)	0.530
KLHDC3	CLUH	psi-mi:“MI:0914”(association)	0.530

BioGRID (335): SYMPK (Biochemical Activity), SYMPK (Affinity Capture-MS), SYMPK (Affinity Capture-MS), SYMPK (Affinity Capture-MS), SYMPK (Affinity Capture-MS), SYMPK (Affinity Capture-MS), CPSF3 (Co-fractionation), CPSF4 (Co-fractionation), SYMPK (Co-fractionation), SYMPK (Co-fractionation), SYMPK (Co-fractionation), USP24 (Co-fractionation), WDR33 (Co-fractionation), SYMPK (Affinity Capture-MS), SYMPK (Two-hybrid)

ESM2 similar proteins: A0JMW6, A1A535, A1A5P5, A1L1L2, A1L2I9, A2BID5, A4FV45, A7Z033, F1QN74, P56695, Q08CY4, Q0KK59, Q14D04, Q2PW47, Q3UHQ6, Q568Z0, Q5FWU8, Q5JWR5, Q5PQS3, Q5SPP5, Q5U249, Q642P2, Q68F70, Q68Y81, Q6DRL5, Q6GPP1, Q6GQ26, Q6IV68, Q6NUQ4, Q6PI53, Q7SYB2, Q7Z3E5, Q7ZYV9, Q80V62, Q80X82, Q8BL99, Q8BM55, Q8CIM8, Q8JGR7, Q8K1H7

Diamond homologs: Q7ZYV9, Q80X82, Q8MSU4, Q92797

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SYMPK	up-regulates	mRNA_polyadenylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Processing of Intronless Pre-mRNAs	11	54.6×	6e-15
RNA Polymerase II Transcription Termination	13	24.8×	5e-13
mRNA 3’-end processing	13	22.3×	2e-12
Transport of Mature mRNA Derived from an Intronless Transcript	6	14.2×	4e-04
mRNA Polyadenylation	18	13.8×	2e-13
Dengue Virus-Host Interactions	19	7.5×	7e-10
Processing of Capped Intron-Containing Pre-mRNA	9	6.4×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA 3’-end processing	8	30.6×	7e-08
mRNA processing	10	5.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	140
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4437 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45815706:C:CT	acceptor_gain	1.0000
19:45815707:G:T	acceptor_gain	1.0000
19:45815846:CCTAC:C	donor_loss	1.0000
19:45815849:A:C	donor_loss	1.0000
19:45816180:CATC:C	acceptor_gain	1.0000
19:45816974:CCTGA:C	acceptor_loss	1.0000
19:45816981:C:CT	acceptor_gain	1.0000
19:45816982:A:T	acceptor_gain	1.0000
19:45817954:GTTAC:G	donor_loss	1.0000
19:45817955:TTAC:T	donor_loss	1.0000
19:45817956:TA:T	donor_loss	1.0000
19:45817957:ACC:A	donor_loss	1.0000
19:45817958:C:CG	donor_loss	1.0000
19:45817958:CCTG:C	donor_gain	1.0000
19:45818127:C:CT	acceptor_gain	1.0000
19:45818142:GGTGG:G	acceptor_gain	1.0000
19:45818143:GTGG:G	acceptor_gain	1.0000
19:45818144:TGG:T	acceptor_gain	1.0000
19:45818146:GC:G	acceptor_loss	1.0000
19:45818147:C:CC	acceptor_gain	1.0000
19:45821378:CCTCA:C	donor_loss	1.0000
19:45821379:CTCAC:C	donor_loss	1.0000
19:45821380:TCAC:T	donor_loss	1.0000
19:45821381:CA:C	donor_loss	1.0000
19:45821383:C:CT	donor_loss	1.0000
19:45821481:CTCAC:C	acceptor_gain	1.0000
19:45821483:CAC:C	acceptor_gain	1.0000
19:45821484:ACC:A	acceptor_loss	1.0000
19:45821486:CTG:C	acceptor_loss	1.0000
19:45821487:T:C	acceptor_loss	1.0000

AlphaMissense

8259 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45816543:A:G	L1098S	1.000
19:45816820:A:T	V1079D	1.000
19:45816832:A:G	L1075P	1.000
19:45816889:A:C	L1056R	1.000
19:45816889:A:G	L1056P	1.000
19:45816909:G:C	S1049R	1.000
19:45816909:G:T	S1049R	1.000
19:45816911:T:G	S1049R	1.000
19:45816925:C:G	R1044P	1.000
19:45816930:G:C	C1042W	1.000
19:45816931:C:T	C1042Y	1.000
19:45816932:A:G	C1042R	1.000
19:45816933:G:C	C1041W	1.000
19:45816934:C:T	C1041Y	1.000
19:45816935:A:G	C1041R	1.000
19:45816936:C:A	K1040N	1.000
19:45816936:C:G	K1040N	1.000
19:45816938:T:C	K1040E	1.000
19:45816942:G:C	F1038L	1.000
19:45816942:G:T	F1038L	1.000
19:45816943:A:C	F1038C	1.000
19:45816943:A:G	F1038S	1.000
19:45816944:A:G	F1038L	1.000
19:45816946:C:A	G1037V	1.000
19:45816946:C:T	G1037D	1.000
19:45816947:C:A	G1037C	1.000
19:45816947:C:G	G1037R	1.000
19:45816947:C:T	G1037S	1.000
19:45816951:C:A	W1035C	1.000
19:45816951:C:G	W1035C	1.000

dbSNP variants (sampled 300 via entrez): RS1000077841 (19:45843031 T>C), RS1000110757 (19:45844626 G>A), RS1000146796 (19:45821610 G>C,T), RS1000159962 (19:45858512 G>A,C), RS1000183332 (19:45823096 G>A), RS1000236347 (19:45817751 G>A,C), RS1000267391 (19:45860944 C>T), RS1000298185 (19:45854010 A>C,G), RS1000351253 (19:45824499 T>G), RS1000366780 (19:45819120 T>C), RS1000457647 (19:45839764 G>A), RS1000463186 (19:45844304 T>A,G), RS1000608028 (19:45832816 C>G), RS1000692608 (19:45863566 TTTTC>T,TTTTCTTTC), RS1000722556 (19:45824300 G>A,C)

Disease associations

OMIM: gene MIM:602388 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004167_1	Colon cancer	2.000000e-08
GCST004167_2	Colon cancer	5.000000e-07
GCST004168_2	Colorectal cancer	9.000000e-07
GCST004606_42	Eosinophil count	2.000000e-17
GCST005196_240	Coronary artery disease	1.000000e-08
GCST007612_3	Chronic obstructive pulmonary disease or coronary artery disease (pleiotropy)	1.000000e-08
GCST009798_38	Asthma	2.000000e-10
GCST90002381_348	Eosinophil count	2.000000e-15
GCST90002382_471	Eosinophil percentage of white cells	6.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066161 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.47	Kd	3.418	nM	CHEMBL5653589
8.47	ED50	3.418	nM	CHEMBL5653589
5.48	IC50	3290	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149532: Binding affinity to human SYMPK incubated for 45 mins by Kinobead based pull down assay	kd	0.0034	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178601: Inhibition of SYMPK (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.2900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	3
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
kojic acid	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
beta-lapachone	increases expression	1
afimoxifene	increases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Fluorouracil	decreases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652574	Binding	Binding affinity to human SYMPK incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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