GSKIP

Summary

GSKIP (GSK3B interacting protein, HGNC:20343) is a protein-coding gene on chromosome 14q32.2, encoding GSK3B-interacting protein (Q9P0R6). A-kinase anchoring protein for GSK3B and PKA that regulates or facilitates their kinase activity towards their targets.

This gene encodes a protein that is involved as a negative regulator of GSK3-beta in the Wnt signaling pathway. The encoded protein may play a role in the retinoic acid signaling pathway by regulating the functional interactions between GSK3-beta, beta-catenin and cyclin D1, and it regulates the beta-catenin/N-cadherin pool. The encoded protein contains a GSK3-beta interacting domain (GID) in its C-terminus, which is similar to the GID of Axin. The protein also contains an evolutionarily conserved RII-binding domain, which facilitates binding with protein kinase-A and GSK3-beta, enabling its role as an A-kinase anchoring protein. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 51527 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• Druggable target: yes
• MANE Select transcript: NM_016472

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20343
Approved symbol	GSKIP
Name	GSK3B interacting protein
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100744
Ensembl biotype	protein_coding
OMIM	616605
Entrez	51527

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding, 1 retained_intron

ENST00000438650, ENST00000553699, ENST00000554182, ENST00000555088, ENST00000555181, ENST00000555757, ENST00000556095, ENST00000852448, ENST00000852449, ENST00000852450, ENST00000852451, ENST00000852452, ENST00000852453, ENST00000915224, ENST00000915225, ENST00000915226, ENST00000915227, ENST00000915228, ENST00000967814, ENST00000967817

RefSeq mRNA: 4 — MANE Select: NM_016472 NM_001271904, NM_001271905, NM_001271906, NM_016472

CCDS: CCDS32153

Canonical transcript exons

ENST00000555181 — 4 exons

Exon	Start	End
ENSE00001175804	96382247	96382505
ENSE00002443496	96363526	96363568
ENSE00002520484	96379688	96379788
ENSE00002533452	96385523	96387288

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6838 / max 188.6881, expressed in 1763 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141337	12.1300	1750
141338	0.5538	291

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.51	gold quality
ileal mucosa	UBERON:0000331	99.33	gold quality
jejunal mucosa	UBERON:0000399	98.29	gold quality
esophagus squamous epithelium	UBERON:0006920	98.23	gold quality
colonic mucosa	UBERON:0000317	98.17	gold quality
palpebral conjunctiva	UBERON:0001812	98.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.06	gold quality
epithelial cell of pancreas	CL:0000083	97.67	gold quality
oocyte	CL:0000023	97.44	gold quality
oral cavity	UBERON:0000167	96.94	gold quality
gingival epithelium	UBERON:0001949	96.87	gold quality
gingiva	UBERON:0001828	96.55	gold quality
endothelial cell	CL:0000115	96.52	gold quality
nasal cavity epithelium	UBERON:0005384	96.49	gold quality
rectum	UBERON:0001052	95.92	gold quality
amniotic fluid	UBERON:0000173	95.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.55	gold quality
duodenum	UBERON:0002114	95.49	gold quality
upper arm skin	UBERON:0004263	95.04	gold quality
upper leg skin	UBERON:0004262	94.16	gold quality
islet of Langerhans	UBERON:0000006	94.12	gold quality
pancreatic ductal cell	CL:0002079	94.11	gold quality
epithelium of nasopharynx	UBERON:0001951	93.99	gold quality
pharyngeal mucosa	UBERON:0000355	93.66	gold quality
mucosa of transverse colon	UBERON:0004991	93.62	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.41	gold quality
pigmented layer of retina	UBERON:0001782	93.25	gold quality
left ventricle myocardium	UBERON:0006566	93.11	gold quality
sperm	CL:0000019	93.00	gold quality
lower esophagus mucosa	UBERON:0035834	92.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	15.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

125 targeting GSKIP, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 9)

• GSKIP is a naturally occurring protein that is homologous with the GSK3beta interaction domain of Axin and is able to negatively regulate GSK3beta of the Wnt signaling pathway. (PMID:16981698)
• analysis of the GSK3beta-GSKIPtide complex structure and the X-ray crystal structures of GSK3beta-FRATide and GSK3beta-AxinGID complexes suggests that the hydroxyl group of Y288 is crucial to maintaining a hydrogen bond network in GSK3beta-FRATide (PMID:21328310)
• demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (PMID:26280900)
• findings highlight an essential compartmentalization of both PKA and GSK3beta by GSKIP, and ascribe a function to a cytosolic AKAP-PKA interaction as a regulatory factor in the control of canonical Wnt signaling. (PMID:27484798)
• Findings support the idea that in addition to its reported role in modulating Drp1, Ser637 phosphorylation causing mitochondrial elongation, GSKIP acts as a scavenger to take GSK3beta away from the beta-catenin destruction complex or as a competitor for GSK3beta binding in the Wnt pathway. (PMID:29694914)
• ATG2B/GSKIP in de novo acute myeloid leukemia (AML): high prevalence of germline predisposition in French West Indies. (PMID:33554699)
• Germline ATG2B/GSKIP-containing 14q32 duplication predisposes to early clonal hematopoiesis leading to myeloid neoplasms. (PMID:34172895)
• Loss of Atg2b and Gskip Impairs the Maintenance of the Hematopoietic Stem Cell Pool Size. (PMID:34748402)
• High expression of GSKIP is associated with poor prognosis in meningioma. (PMID:36550871)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	gskip	ENSDARG00000038099
mus_musculus	Gskip	ENSMUSG00000044715
rattus_norvegicus	Gskip	ENSRNOG00000042427
drosophila_melanogaster	CG14505	FBGN0034327
drosophila_melanogaster	CG11523	FBGN0037156
caenorhabditis_elegans		WBGENE00007357
caenorhabditis_elegans		WBGENE00012813
caenorhabditis_elegans		WBGENE00020782

Protein

Protein identifiers

GSK3B-interacting protein — Q9P0R6 (reviewed: Q9P0R6)

Alternative names: GSK3beta interaction protein

All UniProt accessions (3): Q9P0R6, G3V368, G3V4I5

UniProt curated annotations — full annotation on UniProt →

Function. A-kinase anchoring protein for GSK3B and PKA that regulates or facilitates their kinase activity towards their targets. The ternary complex enhances Wnt-induced signaling by facilitating the GSK3B- and PKA-induced phosphorylation of beta-catenin leading to beta-catenin degradation and stabilization respectively. Upon cAMP activation, the ternary complex contributes to neuroprotection against oxidative stress-induced apoptosis by facilitating the PKA-induced phosphorylation of DML1 and PKA-induced inactivation of GSK3B. During neurite outgrowth promotes neuron proliferation; while increases beta-catenin-induced transcriptional activity through GSK3B kinase activity inhibition, reduces N-cadherin level to promote cell cycle progression.

Subunit / interactions. Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation of GSK3B leading to GSK3B inactivation; recruits DNM1L through GSK3B for PKA-mediated phosphorylation of DNM1L; promotes beta-catenin degradation through GSK3B-induced phosphorylation of beta-catenin; stabilizes beta-catenin and enhances Wnt-induced signaling through PKA-induced phosphorylation of beta-catenin. Interacts with GSK3B; induces GSK3B-mediated phosphorylation of GSKIP and inhibits GSK3B kinase activity.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in heart, brain, placenta, liver, skeletal muscle, kidney, testis, lung and pancreas.

Post-translational modifications. Phosphorylated by GSK3B.

Similarity. Belongs to the GSKIP family.

RefSeq proteins (4): NP_001258833, NP_001258834, NP_001258835, NP_057556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007967	GSKIP_dom	Domain
IPR023231	GSKIP_dom_sf	Homologous_superfamily
IPR037395	GSKIP	Family

Pfam: PF05303

UniProt features (22 total): mutagenesis site 6, strand 6, helix 4, region of interest 3, chain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1SGO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0R6-F1	84.59	0.70

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): 130 (required for gsk3b interaction; contributes to a protective effect against h(2)o(2)-induced apoptosis)

Mutagenesis-validated functional residues (6):

Position	Phenotype
130	loss of interaction with gsk3b. abolishes gsk3b-mediated phosphorylation. prevents beta-catenin accumulation in the cyto
41–45	abolishes interaction with prkar2a and prkar2b. abolishes acquired resistance against oxidative stress-induced apoptosis
42	abolishes interaction with prkar2a. prevents the wnt-induced transcription. does not alter the phosphorylation of ctnnb1
109	no effect on gsk3b-mediated phosphorylation. reduces to 30 % gsk3b-mediated phosphorylation; when associated with a-113.
113	no effect on gsk3b-mediated phosphorylation. reduces to 30 % gsk3b-mediated phosphorylation; when associated with a-109.
115	no effect on gsk3b-mediated phosphorylation. reduces to 30 % gsk3b-mediated phosphorylation; when associated with a-109.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GGGNRMNNYCAT_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, MODULE_239, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (5): negative regulation of protein kinase activity (GO:0006469), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), regulation of Wnt signaling pathway (GO:0030111), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of canonical Wnt signaling pathway (GO:0060828)

GO Molecular Function (6): protein kinase inhibitor activity (GO:0004860), kinase regulator activity (GO:0019207), protein kinase binding (GO:0019901), protein kinase A regulatory subunit binding (GO:0034237), protein kinase A binding (GO:0051018), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
canonical Wnt signaling pathway	2
negative regulation of protein phosphorylation	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
intrinsic apoptotic signaling pathway	1
regulation of signal transduction	1
Wnt signaling pathway	1
positive regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
kinase inhibitor activity	1
protein kinase regulator activity	1
kinase activity	1
enzyme regulator activity	1
kinase binding	1
protein kinase A binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSKIP	GSK3B	P49841	912
GSKIP	ATG2B	Q96BY7	783
GSKIP	PRKACA	P17612	764
GSKIP	PRKACG	P22612	764
GSKIP	PRKACB	P22694	763
GSKIP	PRKAR2B	P31323	464
GSKIP	BCORL1	Q5H9F3	440
GSKIP	PRKAR2A	P13861	427
GSKIP	FAM228B	P0C875	403
GSKIP	RBBP6	Q7Z6E9	392
GSKIP	AKAP1	Q92667	387
GSKIP	AKAP11	Q9UKA4	354
GSKIP	KCTD18	Q6PI47	354
GSKIP	PIN1	Q13526	346
GSKIP	AKAP13	Q12802	335
GSKIP	HBS1L	Q9Y450	335

IntAct

18 interactions, top by confidence:

A	B	Type	Score
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
GSKIP	GSK3A	psi-mi:“MI:0915”(physical association)	0.800
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
GSKIP	GSK3A	psi-mi:“MI:0914”(association)	0.800
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
GSK3B	SEC16A	psi-mi:“MI:0914”(association)	0.420
GSKIP	EXT2	psi-mi:“MI:0915”(physical association)	0.370
PEX19	GSKIP	psi-mi:“MI:0915”(physical association)	0.370
MAPT	PRKAR2A	psi-mi:“MI:0914”(association)	0.350
GSK3B	MYO1C	psi-mi:“MI:0914”(association)	0.350
GSKIP	A2ML1	psi-mi:“MI:0914”(association)	0.350
GSKIP	RP2	psi-mi:“MI:0914”(association)	0.350
SMYD2	GSKIP	psi-mi:“MI:0915”(physical association)	0.000
GSK3B	GSKIP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): GSKIP (Affinity Capture-RNA), GSKIP (Affinity Capture-MS), GSKIP (Affinity Capture-MS), GSKIP (Affinity Capture-RNA), GSKIP (Affinity Capture-MS), GSKIP (Proximity Label-MS), KPRP (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), HAVCR2 (Affinity Capture-MS), PMEL (Affinity Capture-MS), LOR (Affinity Capture-MS), GM2A (Affinity Capture-MS), CPA4 (Affinity Capture-MS), GSK3B (Affinity Capture-MS), PLS1 (Affinity Capture-MS)

ESM2 similar proteins: A1L251, A2XV58, A4IIW5, A8XEZ1, B4J613, C5DLJ0, E5KGE0, F4JIN3, O13648, O43035, O76240, O80996, P34511, P50244, P91133, P93043, Q0JC10, Q0P5A3, Q0WT48, Q0WVD6, Q19954, Q25264, Q39677, Q42829, Q4R812, Q5PPI3, Q5ZMC6, Q6C710, Q7XVN7, Q7YTB0, Q7ZWI4, Q80UP5, Q8BGR8, Q8IZ07, Q8LI34, Q8STE5, Q8T913, Q95QN6, Q9FLF7, Q9FQ09

Diamond homologs: A4IIW5, Q0P5A3, Q4R812, Q5PPI3, Q5ZMC6, Q7ZWI4, Q8BGR8, Q9P0R6, Q9V8F3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

712 predictions. Top by Δscore:

Variant	Effect	Δscore
14:96363566:CAGG:C	donor_loss	1.0000
14:96363567:AGGTG:A	donor_loss	1.0000
14:96363568:GGT:G	donor_loss	1.0000
14:96363569:GTG:G	donor_loss	1.0000
14:96363570:T:A	donor_loss	1.0000
14:96379686:AGCTC:A	acceptor_gain	1.0000
14:96379687:GCTCG:G	acceptor_gain	1.0000
14:96382241:TTACA:T	acceptor_gain	1.0000
14:96382242:TACAG:T	acceptor_gain	1.0000
14:96382243:A:AG	acceptor_gain	1.0000
14:96382243:ACAG:A	acceptor_gain	1.0000
14:96382244:C:G	acceptor_gain	1.0000
14:96382244:CAGAA:C	acceptor_gain	1.0000
14:96382245:A:AG	acceptor_gain	1.0000
14:96382245:AGAA:A	acceptor_gain	1.0000
14:96382245:AGAAT:A	acceptor_gain	1.0000
14:96382246:G:GA	acceptor_gain	1.0000
14:96382246:GA:G	acceptor_gain	1.0000
14:96382246:GAA:G	acceptor_gain	1.0000
14:96382246:GAAT:G	acceptor_gain	1.0000
14:96382246:GAATG:G	acceptor_gain	1.0000
14:96382365:GTT:G	donor_gain	1.0000
14:96382461:G:GT	donor_gain	1.0000
14:96382462:A:T	donor_gain	1.0000
14:96382501:TCAAG:T	donor_loss	1.0000
14:96382502:CAAGG:C	donor_loss	1.0000
14:96382503:AAGGT:A	donor_loss	1.0000
14:96382504:AGG:A	donor_loss	1.0000
14:96382505:GGT:G	donor_loss	1.0000
14:96382506:GT:G	donor_loss	1.0000

AlphaMissense

913 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:96385628:T:C	F122L	1.000
14:96385630:T:A	F122L	1.000
14:96385630:T:G	F122L	1.000
14:96382486:T:C	L80P	0.999
14:96385607:A:C	S115R	0.999
14:96385609:C:A	S115R	0.999
14:96385609:C:G	S115R	0.999
14:96382356:G:C	A37P	0.998
14:96382362:G:C	A39P	0.998
14:96382387:C:A	A47D	0.998
14:96382390:T:A	V48D	0.998
14:96382480:T:C	L78P	0.998
14:96382498:G:A	G84E	0.998
14:96385581:C:T	T106I	0.998
14:96385596:T:C	L111S	0.998
14:96385616:T:G	Y118D	0.998
14:96385629:T:G	F122C	0.998
14:96385641:T:A	L126Q	0.998
14:96385641:T:C	L126P	0.998
14:96382357:C:A	A37D	0.997
14:96382366:T:A	V40D	0.997
14:96382444:T:A	I66N	0.997
14:96382450:T:A	V68E	0.997
14:96382501:T:C	L85P	0.997
14:96385584:T:A	V107D	0.997
14:96385629:T:C	F122S	0.997
14:96385653:T:C	L130P	0.997
14:96382378:T:A	V44D	0.996
14:96385578:A:T	E105V	0.996
14:96385616:T:C	Y118H	0.996

dbSNP variants (sampled 300 via entrez): RS1000064310 (14:96370402 G>A), RS1000093577 (14:96370018 C>G,T), RS1000178132 (14:96375821 G>T), RS1000212045 (14:96376903 A>T), RS1000240449 (14:96370978 A>C), RS1000301127 (14:96370748 A>G), RS1000345696 (14:96383135 C>A,G), RS1000350868 (14:96364815 C>G), RS1000408770 (14:96363356 C>A), RS1000419344 (14:96382836 C>T), RS1000624345 (14:96383543 A>C), RS1000647410 (14:96376546 A>G), RS1000780056 (14:96377249 T>A,C), RS1001012442 (14:96364406 A>G,T), RS1001065761 (14:96371823 G>A)

Disease associations

OMIM: gene MIM:616605 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004720_9	Conotruncal heart defects (inherited effects)	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067425 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.61	Kd	24.35	nM	CHEMBL3752910
7.54	ED50	29.07	nM	CHEMBL3752910
5.82	Kd	1515	nM	CHEMBL5653589
5.74	ED50	1810	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148465: Binding affinity to human GSKIP incubated for 45 mins by Kinobead based pull down assay	kd	0.0244	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148465: Binding affinity to human GSKIP incubated for 45 mins by Kinobead based pull down assay	kd	1.5154	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	2
dicrotophos	decreases expression	1
bisphenol A	decreases methylation	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
clothianidin	increases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651507	Binding	Binding affinity to human GSKIP 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

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8M8	Ubigene HCT 116 GSKIP KO	Cancer cell line	Male
CVCL_E1YQ	HAP1 GSKIP (-) 2	Cancer cell line	Male
CVCL_XP41	HAP1 GSKIP (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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