KPNA2

Summary

KPNA2 (karyopherin subunit alpha 2, HGNC:6395) is a protein-coding gene on chromosome 17q24.2, encoding Importin subunit alpha-1 (P52292). Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. It is a selective cancer dependency (DepMap: 20.8% of cell lines).

The import of proteins into the nucleus is a process that involves at least 2 steps. The first is an energy-independent docking of the protein to the nuclear envelope and the second is an energy-dependent translocation through the nuclear pore complex. Imported proteins require a nuclear localization sequence (NLS) which generally consists of a short region of basic amino acids or 2 such regions spaced about 10 amino acids apart. Proteins involved in the first step of nuclear import have been identified in different systems. These include the Xenopus protein importin and its yeast homolog, SRP1 (a suppressor of certain temperature-sensitive mutations of RNA polymerase I in Saccharomyces cerevisiae), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3838 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 51 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 20.8% of screened cell lines
• MANE Select transcript: NM_002266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6395
Approved symbol	KPNA2
Name	karyopherin subunit alpha 2
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	SRP1alpha, IPOA1, QIP2, PTAC58
Ensembl gene	ENSG00000182481
Ensembl biotype	protein_coding
OMIM	600685
Entrez	3838

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 19 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000330459, ENST00000537025, ENST00000579754, ENST00000582898, ENST00000583269, ENST00000583392, ENST00000584026, ENST00000676594, ENST00000676622, ENST00000676857, ENST00000676902, ENST00000677086, ENST00000677223, ENST00000677419, ENST00000677695, ENST00000677827, ENST00000677918, ENST00000678054, ENST00000678388, ENST00000679078, ENST00000679346, ENST00000913633, ENST00000913634, ENST00000913635, ENST00000913636, ENST00000913637, ENST00000913638, ENST00000913639, ENST00000913640, ENST00000913641, ENST00000964619

RefSeq mRNA: 2 — MANE Select: NM_002266 NM_001320611, NM_002266

CCDS: CCDS32713

Canonical transcript exons

ENST00000330459 — 11 exons

Exon	Start	End
ENSE00001643282	68042905	68042999
ENSE00001673356	68035735	68035840
ENSE00001684697	68042085	68042353
ENSE00001712528	68044321	68044503
ENSE00001723038	68043100	68043363
ENSE00002522248	68043838	68044071
ENSE00002523200	68037358	68037495
ENSE00002686869	68037110	68037207
ENSE00003610966	68045772	68045921
ENSE00003680039	68040678	68040766
ENSE00003850465	68046504	68046854

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 268.1675 / max 3002.7430, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162361	250.0390	1825
162360	12.6963	1756
162362	4.1250	1209
162363	0.8923	472
162364	0.4150	196

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.96	gold quality
left testis	UBERON:0004533	98.82	gold quality
right testis	UBERON:0004534	98.81	gold quality
ganglionic eminence	UBERON:0004023	98.77	gold quality
testis	UBERON:0000473	98.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.16	gold quality
stromal cell of endometrium	CL:0002255	96.77	gold quality
vermiform appendix	UBERON:0001154	95.30	gold quality
lymph node	UBERON:0000029	95.05	gold quality
islet of Langerhans	UBERON:0000006	94.91	gold quality
placenta	UBERON:0001987	94.82	gold quality
mucosa of transverse colon	UBERON:0004991	94.62	gold quality
endometrium	UBERON:0001295	94.42	gold quality
cortical plate	UBERON:0005343	94.34	gold quality
bone marrow	UBERON:0002371	93.97	gold quality
esophagus mucosa	UBERON:0002469	92.84	gold quality
smooth muscle tissue	UBERON:0001135	92.77	gold quality
rectum	UBERON:0001052	92.69	gold quality
lower esophagus mucosa	UBERON:0035834	92.24	gold quality
adrenal tissue	UBERON:0018303	92.04	gold quality
superior frontal gyrus	UBERON:0002661	91.83	gold quality
prefrontal cortex	UBERON:0000451	91.56	gold quality
bone marrow cell	CL:0002092	91.28	gold quality
frontal cortex	UBERON:0001870	90.76	gold quality
duodenum	UBERON:0002114	90.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.42	gold quality
cerebral cortex	UBERON:0000956	90.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.30	gold quality
hypothalamus	UBERON:0001898	90.23	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	7399.35
E-MTAB-7052	yes	2676.57
E-MTAB-10290	yes	801.83
E-GEOD-134144	yes	29.07
E-HCAD-10	yes	27.09
E-HCAD-13	yes	21.18
E-MTAB-9388	yes	11.16
E-MTAB-6911	no	4216.56
E-MTAB-7008	no	2325.06
E-MTAB-6524	no	1195.16
E-MTAB-9689	no	540.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF2, KLF4, YBX1

miRNA regulators (miRDB)

71 targeting KPNA2, 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-3692-3P	99.98	70.27	2139
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-LET-7G-3P	99.85	70.43	1929

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Characterization of an unusual importin alpha binding motif in the borna disease virus p10 protein that directs nuclear import (PMID:11796712)
• Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal (PMID:11882654)
• HPV16 E6 interacts with the karyopherin alpha2 adapter and can enter the nucleus of hela cells via a classical Kap alpha2beta1-mediated pathway (PMID:12551970)
• IPOA1 was localized at the lymphocyte plasma membrane. Its subcellular distribution was also studied. (PMID:12883947)
• confirmed the role of KPNA-2 in nuclear import of Chk2 (PMID:12909615)
• Importin alpha/beta-mediated nuclear import machinery is regulated in a cell cycle-dependent manner through the modulation of interaction modes between importins alpha and beta. (PMID:15194443)
• interaction with importin system is required for thioredoxin-binding protein-2 nuclear translocation and growth control tightly associated with TRX-dependent redox regulation of transcription factors (PMID:15234975)
• Results point to importin alpha1 as a critical downstream target of AMP-activated protein kinase (AMPK) and key mediator of AMPK-triggered HuR nuclear import. (PMID:15342649)
• These observations indicate that importin-alpha functions as a mediator for the nuclear entry of Vpr. (PMID:15731250)
• The model reflects experimentally determined rates for cargo import and correctly predicts that import is limited principally by Impalpha and Ran, but is also sensitive to NTF2 (PMID:15795315)
• an interaction with KPNA2 contributes to nuclear localization and multiple tumor suppression functions of the NBS1 complex (PMID:16188882)
• These data suggest the importance of receptor endocytosis, endosomal sorting machinery, interaction with importins alpha1/beta1, and exportin CRM1 in EGFR nuclear-cytoplasmic trafficking. (PMID:16552725)
• This review focuses on recent experimental evidences demonstrating how NBS1 is translocated into the nucleus by an importin KPNA2 which mediates NBS1 subcellular localization and the functions of the NBS1 complex in tumorigenesis. (PMID:16752129)
• The gene expression profiling of laser-microdissected breast cancer tissue revealed KPNA2 genes that may represent potential molecular targets for breast cancer therapy and prediction of outcome. (PMID:16818692)
• importin alpha1, an essential component of cytoplasmic-nuclear transport, is abnormally accumulated in Hirano bodies in vulnerable hippocampal neurons in AD. (PMID:17070506)
• KPNA2 may play an important role in the signal-transduction pathways that regulate epidermal proliferation and differentiation (PMID:17255955)
• interaction between importin alpha and the N-terminal alpha-helical domain of Vpr is indispensable, not only for the nuclear import of Vpr but also for HIV-1 replication in macrophages. (PMID:17344301)
• dengue virus nonstructural protein 5 nuclear localization through its importin alpha/beta-recognized nuclear localization sequences is integral to viral infection (PMID:17537211)
• The data, together with previous analyses of nuclear protein import, suggest that the use of adapters such as importin-alpha provides the cell with increased dynamic range for control of nuclear import rates, but at the expense of efficiency. (PMID:17551513)
• SARS-COV ORF6 protein is localized to the endoplasmic reticulum (ER)/Golgi membrane in infected cells, where it binds to and disrupts nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane. (PMID:17596301)
• Expression of KPNA2 in invasive breast cancer correlates with conventional prognostic parameters & shorter disease-free survival. KPNA2 is overexpressed in DCIS, which emphasizes its potential role in carcinogenesis of invasive breast carcinomas. (PMID:17899179)
• The formation of high molecular mass complexes containing importin-alpha, Nup153 and Nup88 is increased upon oxidant treatment. (PMID:18068677)
• KPNA2 nuclear expression as novel prognostic marker in node-positive breast cancer patients (PMID:18561322)
• Oct4 nuclear localization may be mediated by its interaction with KPNA-2. (PMID:19103427)
• Crm1, Kpnbeta1 and Kpnalpha2 are overexpressed in cervical cancer and inhibiting the expression of Crm1 and Kpnbeta1, not Kpnalpha2, induces cancer cell death (PMID:19117056)
• The tripartite protein-RNA complex formation between Hexim, Cyclin T and 7SK snRNA, was analyzed. (PMID:19883659)
• nuclear import of HIV-1 integrase(IN) occurs via importin alpha pathway and promoted by a specific nuclear localization signal(NLS).Import could be blocked by NLS-IN peptide confirming that nuclear import of viral preintegration complex is mediated by IN. (PMID:19961612)
• Data reveal the involvement of importin alpha1 in the assembly of RNA granules and its pro-survival role during stress (PMID:20362631)
• KPNA2 expression is associated with poor differentiation, tumor invasiveness, and tumor proliferation in esophageal squamous cell carcinoma. (PMID:20393006)
• protein levels of KPNA2 in pleural effusion from NSCLC patients were also significantly higher than those from non-lung cancer. Moreover, knockdown of KPNA2 inhibited the migration ability and viability of lung cancer cells (PMID:20658535)
• Overexpression of KPNA2 in patients with epithelial ovarian cancer is positively associated with an epithelial ovarian cancer-specific histologic type and a poor prognosis. (PMID:20859152)
• KPNA2 expression was significantly upregulated in carcinomas of the prostate, especially in metastatic and castration-resistant prostate cancer samples; it is a novel independent prognostic marker for disease progression after radical prostatectomy (PMID:21220479)
• Overexpression of importin alpha1 is associated with hepatocellular carcinoma. (PMID:21286940)
• Transportin 3 and importin alpha act as receptors and are required for effective nuclear import of HIV-1 integrase in virus-infected cells. (PMID:21326825)
• KPNA2 expression is a marker for progression of non-muscle-invasive bladder cancer and a prognostic marker in patients undergoing radical cystectomy. (PMID:21330047)
• Taspase1 appears to exploit the nuclear export activity of importin-alpha/nucleophosmin to gain transient access to the cytoplasm required to also cleave its cytoplasmic substrates. (PMID:21418451)
• importin alpha interacted with the zinc finger domain of Snail to compete with the binding of importin beta1 and Snail did not form a ternary complex with importin alpha/importin beta1. (PMID:21454664)
• Crystallographic analysis of mammalian importin alpha1 in complex with the hPLSCR4-NLS reveals this minimal NLS binds specifically and exclusively to the minor binding site of importin alpha (PMID:21690087)
• This study gives clear evidence that KPNA2 acts as a novel oncogenic factor in human breast cancer, in vitro. (PMID:21909132)
• findings suggest that the deregulated activity of E2F in cancer cells causes increased activation of the Kpnbeta1 and Kpnalpha2 promoters, leading to elevated levels of these proteins, and ultimately impacting the cancer phenotype. (PMID:22125623)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	kpna2	ENSDARG00000038066
mus_musculus	Kpna2	ENSMUSG00000018362
mus_musculus	Kpna2rt	ENSMUSG00000066878
rattus_norvegicus	Kpna2	ENSRNOG00000015329
rattus_norvegicus	Kpna2l1	ENSRNOG00000030058
rattus_norvegicus		ENSRNOG00000069417
caenorhabditis_elegans		WBGENE00002072
caenorhabditis_elegans		WBGENE00009956

Paralogs (6): KPNA6 (ENSG00000025800), KPNA3 (ENSG00000102753), KPNA1 (ENSG00000114030), KPNA7 (ENSG00000185467), KPNA4 (ENSG00000186432), KPNA5 (ENSG00000196911)

Protein

Protein identifiers

Importin subunit alpha-1 — P52292 (reviewed: P52292)

Alternative names: Karyopherin subunit alpha-2, RAG cohort protein 1, SRP1-alpha

All UniProt accessions (8): P52292, A0A7I2V351, A0A7I2V3Z3, A0A7I2V487, A0A7I2YQE1, J3KS65, J3QL07, J3QLL0

UniProt curated annotations — full annotation on UniProt →

Function. Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediator of PR-DUB complex component BAP1 nuclear import; acts redundantly with KPNA1 and Transportin-1/TNPO1.

Subunit / interactions. Heterodimer; with KPNB1. Interacts with ANP32E. Component of a complex containing CSE1L, RAN and KPNA2. Interacts directly with CSE1L. Interacts with PLAG1. Interacts with APEX1 (via N-terminus). Interacts with FRG1 (via N-terminus). Interacts with ARL4A, CTNNBL1 and NBN. Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc fingers). Interacts with BAG6. Interacts with AIFM2; this interaction likely mediates the translocation of AIFM2 into the nucleus upon oxidative stress. Interacts with RSL1D1. Interacts with BAP1 (via C-terminus); the interaction contributes to BAP1 nuclear localization. Interacts with PLSCR4; this interaction mediates the nucleus import of PLSCR4. (Microbial infection) Interacts with HIV-1 Vpr. (Microbial infection) Interacts with vaccinia virus protein KBTB1. (Microbial infection) Part of a tetrameric complex composed of CRM1, importin alpha/beta dimer and the Venezuelan equine encephalitis virus (VEEV) capsid; this complex blocks the receptor-mediated transport through the nuclear pore. (Microbial infection) Interacts with SARS-COV virus ORF6 protein; this interaction blocks the receptor-mediated transport through the nuclear pore. (Microbial infection) Interacts with Zika virus RNA-directed RNA polymerase NS5. (Microbial infection) Interacts with SARS-CoV-2 ORF6 protein; this interaction may inhibit IFN-beta production by blocking IRF3 nuclear translocation. (Microbial infection) Interacts with Epstein-Barr virus EBNA1; this interaction allows the nuclear import of EBNA1.

Subcellular location. Cytoplasm. Nucleus Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Expressed ubiquitously.

Post-translational modifications. Ubiquitinated. Deubiquitinated by USP22; leading to stabilization and increased activity.

Domain organisation. Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import. The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins. The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding.

Similarity. Belongs to the importin alpha family.

RefSeq proteins (2): NP_001307540, NP_002257* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR002652	Importin-a_IBB	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024931	Importin_alpha	Family
IPR032413	Arm_3	Repeat
IPR036975	Importin-a_IBB_sf	Homologous_superfamily

Pfam: PF00514, PF01749, PF16186

UniProt features (69 total): helix 35, repeat 10, region of interest 4, sequence variant 4, modified residue 3, mutagenesis site 3, turn 2, strand 2, initiator methionine 1, chain 1, short sequence motif 1, compositionally biased region 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
4WV6	X-RAY DIFFRACTION	1.75
8FZK	X-RAY DIFFRACTION	2.1
3FEY	X-RAY DIFFRACTION	2.2
7N9H	X-RAY DIFFRACTION	2.2
1QGR	X-RAY DIFFRACTION	2.3
5H43	X-RAY DIFFRACTION	2.3
1QGK	X-RAY DIFFRACTION	2.5
4E4V	X-RAY DIFFRACTION	2.53
3WPT	X-RAY DIFFRACTION	2.63
7CRU	X-RAY DIFFRACTION	2.8
1EFX	X-RAY DIFFRACTION	3
7N8J	X-RAY DIFFRACTION	3.2
9BFC	ELECTRON MICROSCOPY	3.2
9N86	ELECTRON MICROSCOPY	3.3
3FEX	X-RAY DIFFRACTION	3.55
9B4Y	ELECTRON MICROSCOPY	3.74
8GCN	ELECTRON MICROSCOPY	3.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52292-F1	86.12	0.77

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 (3): 2, 62, 490

Mutagenesis-validated functional residues (3):

Position	Phenotype
2–80	complete loss of binding to kpnb1.
192	does not affect association with kat8 target protein.
396	decreased association with kat8 target protein.

Function

Pathways and Gene Ontology

Reactome pathways

44 pathways

ID	Pathway
R-HSA-111932	CaMK IV-mediated phosphorylation of CREB
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-442729	CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde
R-HSA-5693548	Sensing of DNA Double Strand Breaks
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9918432	Maturation of DENV proteins
R-HSA-111885	Opioid Signalling
R-HSA-111933	Calmodulin induced events
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-418594	G alpha (i) signalling events
R-HSA-438064	Post NMDA receptor activation events
R-HSA-442755	Activation of NMDA receptors and postsynaptic events

MSigDB gene sets: 441 (showing top): GOBP_REGULATION_OF_DNA_RECOMBINATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, MODULE_451, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MCLACHLAN_DENTAL_CARIES_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CREB1_PHOSPHORYLATION_THROUGH_THE_ACTIVATION_OF_CAMKII_CAMKK_CAMKIV_CASCASDE, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, PAL_PRMT5_TARGETS_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_RAD21

GO Biological Process (10): regulation of DNA recombination (GO:0000018), DNA metabolic process (GO:0006259), protein import into nucleus (GO:0006606), NLS-bearing protein import into nucleus (GO:0006607), positive regulation of type I interferon production (GO:0032481), entry of viral genome into host nucleus through nuclear pore complex via importin (GO:0075506), positive regulation of viral life cycle (GO:1903902), protein transport (GO:0015031), non-canonical NF-kappaB signal transduction (GO:0038061), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (5): RNA binding (GO:0003723), nuclear localization sequence binding (GO:0008139), histone deacetylase binding (GO:0042826), nuclear import signal receptor activity (GO:0061608), protein binding (GO:0005515)

GO Cellular Component (12): Golgi membrane (GO:0000139), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), NLS-dependent protein nuclear import complex (GO:0042564), host cell (GO:0043657), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
Calmodulin induced events	1
Antimicrobial mechanism of IFN-stimulated genes	1
Influenza Infection	1
Post NMDA receptor activation events	1
DNA Double Strand Break Response	1
ESR-mediated signaling	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Dengue Virus Genome Translation and Replication	1
G alpha (i) signalling events	1
CaM pathway	1
PLC beta mediated events	1
Ca-dependent events	1
DAG and IP3 signaling	1
Opioid Signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
cytoplasm	3
import into nucleus	2
organelle membrane	2
endomembrane system	2
DNA recombination	1
regulation of DNA metabolic process	1
nucleic acid metabolic process	1
intracellular protein transport	1
protein localization to nucleus	1
establishment of protein localization to organelle	1
protein import into nucleus	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
viral penetration into host nucleus	1
viral life cycle	1
positive regulation of viral process	1
regulation of viral life cycle	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
intracellular signaling cassette	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
signal sequence receptor activity	1
enzyme binding	1
nucleocytoplasmic carrier activity	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
nucleus	1
nuclear envelope	1

Protein interactions and networks

STRING

4154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KPNA2	KPNB1	Q14974	966
KPNA2	PHGDH	O43175	824
KPNA2	NUP153	P49790	787
KPNA2	RECQL	P46063	779
KPNA2	STAT1	P42224	754
KPNA2	RCC1	P18754	753
KPNA2	XPO1	O14980	742
KPNA2	CSE1L	P55060	741
KPNA2	TNPO1	Q92973	719
KPNA2	TXNIP	Q9H3M7	697
KPNA2	SLC2A2	P11168	682
KPNA2	IPO5	O00410	676
KPNA2	HNRNPK	P61978	673
KPNA2	NUP62	P37198	663
KPNA2	INTS9	Q9NV88	660

IntAct

482 interactions, top by confidence:

A	B	Type	Score
KPNB1	KPNA2	psi-mi:“MI:0407”(direct interaction)	0.930
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
NUP50	KPNA2	psi-mi:“MI:0915”(physical association)	0.870
KPNA2	NUP50	psi-mi:“MI:0915”(physical association)	0.870
KPNA2	MLH1	psi-mi:“MI:0915”(physical association)	0.830
MLH1	KPNA2	psi-mi:“MI:0915”(physical association)	0.830
KPNA2	NUP153	psi-mi:“MI:0914”(association)	0.790
NMNAT1	KPNA2	psi-mi:“MI:0915”(physical association)	0.780
KPNA2	NMNAT1	psi-mi:“MI:0915”(physical association)	0.780
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
KPNB1	KPNA2	psi-mi:“MI:0407”(direct interaction)	0.700
MTA2	KPNA2	psi-mi:“MI:0914”(association)	0.690
KPNA2	MTA2	psi-mi:“MI:0914”(association)	0.690

BioGRID (733): KPNA2 (Affinity Capture-MS), KPNA2 (Affinity Capture-MS), KPNA2 (Two-hybrid), KPNA2 (Two-hybrid), MDFI (Two-hybrid), MLH1 (Two-hybrid), TADA2A (Two-hybrid), MAGED1 (Two-hybrid), HMG20A (Two-hybrid), NUP50 (Two-hybrid), RBPMS (Two-hybrid), NUP62 (Two-hybrid), SERTAD3 (Two-hybrid), NECAB2 (Two-hybrid), TRIM54 (Two-hybrid)

ESM2 similar proteins: A2BFL2, A9QM74, B6HJ92, B8ARW2, B9FDR3, C0LLJ0, C1JZ66, C6K7I2, F4JL11, G5EB89, O00505, O00629, O04294, O14063, O14089, O22478, O35343, O35344, O43747, O60518, O75843, O80480, O88512, O94374, P22892, P52170, P52171, P52292, P52293, P52295, P91276, Q02821, Q19969, Q23924, Q557F4, Q5R5M2, Q5RAG3, Q6DGR4, Q71VM4, Q76P29

Diamond homologs: A2VE08, A9QM74, B6HJ92, C0LLJ0, C1JZ66, C6K7I2, F4JL11, G5EB89, O00505, O00629, O04294, O14063, O15131, O22478, O35343, O35344, O35345, O60684, O80480, O94374, P52170, P52171, P52292, P52293, P52294, P52295, P83953, P91276, Q02821, Q0V7M0, Q19969, Q503E9, Q557F4, Q56R16, Q5R909, Q5RBV0, Q5ZML1, Q60960, Q71VM4, Q76P29

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
EP300	up-regulates	KPNA2	acetylation
PRKAA1	up-regulates	KPNA2	phosphorylation
AMPK	up-regulates	KPNA2	phosphorylation
6	“down-regulates activity”	KPNA2	binding
KPNA2	“up-regulates activity”	IRF3	relocalization
KPNA2	“down-regulates activity”	RNMT	binding
ORF6	“down-regulates activity”	KPNA2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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
NS1 Mediated Effects on Host Pathways	7	31.2×	1e-06
Transport of the SLBP independent Mature mRNA	6	30.6×	8e-06
Transport of the SLBP Dependant Mature mRNA	6	29.7×	8e-06
Transport of Ribonucleoproteins into the Host Nucleus	5	27.9×	4e-05
Nuclear import of Rev protein	5	26.2×	6e-05
Transport of Mature mRNA Derived from an Intronless Transcript	6	25.5×	1e-05
Viral Messenger RNA Synthesis	5	20.3×	2e-04
snRNP Assembly	6	19.8×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	5	44.6×	2e-05
protein import into nucleus	11	17.6×	3e-08
double-strand break repair	5	11.3×	5e-03
chromatin remodeling	9	7.3×	7e-04
transcription by RNA polymerase II	8	6.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

977 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68035836:CGCAG:C	donor_loss	1.0000
17:68035838:CAG:C	donor_loss	1.0000
17:68035839:AGGT:A	donor_loss	1.0000
17:68035840:GG:G	donor_loss	1.0000
17:68035841:GT:G	donor_loss	1.0000
17:68035842:T:G	donor_loss	1.0000
17:68037102:T:G	acceptor_gain	1.0000
17:68037105:TTTAG:T	acceptor_loss	1.0000
17:68037106:TTA:T	acceptor_loss	1.0000
17:68037107:TA:T	acceptor_loss	1.0000
17:68037108:A:AG	acceptor_gain	1.0000
17:68037108:AGCTT:A	acceptor_loss	1.0000
17:68037109:G:GC	acceptor_gain	1.0000
17:68037109:GC:G	acceptor_gain	1.0000
17:68037109:GCT:G	acceptor_gain	1.0000
17:68037109:GCTTT:G	acceptor_gain	1.0000
17:68037203:GTACA:G	donor_gain	1.0000
17:68037204:TACA:T	donor_gain	1.0000
17:68037208:G:GG	donor_gain	1.0000
17:68037353:TCAA:T	acceptor_loss	1.0000
17:68037354:CAAG:C	acceptor_loss	1.0000
17:68037355:A:AG	acceptor_gain	1.0000
17:68037355:AAG:A	acceptor_gain	1.0000
17:68037356:A:AG	acceptor_gain	1.0000
17:68037357:G:A	acceptor_gain	1.0000
17:68037357:G:GG	acceptor_gain	1.0000
17:68037357:GGA:G	acceptor_gain	1.0000
17:68037357:GGAA:G	acceptor_gain	1.0000
17:68037494:AGGTA:A	donor_loss	1.0000
17:68037495:GGTA:G	donor_loss	1.0000

AlphaMissense

3469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:68037398:G:C	R39T	1.000
17:68037398:G:T	R39M	1.000
17:68037399:G:C	R39S	1.000
17:68037399:G:T	R39S	1.000
17:68037429:G:C	K49N	1.000
17:68037429:G:T	K49N	1.000
17:68037431:G:C	R50T	1.000
17:68037431:G:T	R50M	1.000
17:68037432:G:C	R50S	1.000
17:68037432:G:T	R50S	1.000
17:68037434:G:C	R51T	1.000
17:68037434:G:T	R51I	1.000
17:68037435:A:C	R51S	1.000
17:68037435:A:T	R51S	1.000
17:68040763:C:A	A100D	1.000
17:68040766:G:C	R101T	1.000
17:68040766:G:T	R101M	1.000
17:68042085:G:C	R101S	1.000
17:68042085:G:T	R101S	1.000
17:68042093:T:A	L104H	1.000
17:68042093:T:C	L104P	1.000
17:68042194:T:C	F138L	1.000
17:68042195:T:C	F138S	1.000
17:68042196:T:A	F138L	1.000
17:68042196:T:G	F138L	1.000
17:68042197:G:A	E139K	1.000
17:68042198:A:T	E139V	1.000
17:68042203:G:C	A141P	1.000
17:68042204:C:A	A141D	1.000
17:68042206:T:A	W142R	1.000

dbSNP variants (sampled 300 via entrez): RS1000154396 (17:68034023 G>A,C), RS1000986051 (17:68041311 C>G), RS1001085951 (17:68035195 A>C), RS1001159575 (17:68035699 G>A), RS1001355036 (17:68041038 G>T), RS1001956353 (17:68042521 A>T), RS1002085356 (17:68036651 C>G), RS1002392457 (17:68042698 C>T), RS1004515668 (17:68034489 G>C), RS1005056327 (17:68040260 A>T), RS1005539647 (17:68040587 G>A,C), RS1006469044 (17:68041690 C>T), RS1006533032 (17:68037558 T>C), RS1006563667 (17:68037867 C>T), RS1007548002 (17:68043421 C>A,T)

Disease associations

OMIM: gene MIM:600685 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST006922_1	Regular attendance at a religious group	2.000000e-06
GCST006923_7	Loneliness	6.000000e-09
GCST006924_5	Loneliness (MTAG)	1.000000e-09
GCST006942_4	Feeling lonely	3.000000e-08
GCST007325_237	General risk tolerance (MTAG)	5.000000e-09
GCST010002_130	Refractive error	7.000000e-12
GCST010703_274	Brain morphology (MOSTest)	1.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1741187 (SINGLE PROTEIN), CHEMBL6195522 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195538 (PROTEIN-PROTEIN INTERACTION)

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)

Binding affinities (BindingDB)

390 measured of 947 human assays (1011 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-methoxypropan-2-yl 2-amino-1-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxylate	EC50	0.00352 nM
MLS000116741	EC50	0.0402 nM
3-[2-(2-methoxyphenyl)ethynyl]-10-methylacridin-9-one	EC50	720 nM
(E)-1-(3,4-dimethoxyphenyl)-3-[(6-methyl-2-pyridinyl)amino]-2-propen-1-one	EC50	749 nM
2-Cyano-N-[2-(1H-indol-3-yl)-ethyl]-3-(5-piperidin-1-yl-furan-2-yl)-acrylamide	EC50	753 nM
SMR000046228	EC50	862 nM
cid_1932059	EC50	918 nM
SMR000040521	EC50	932 nM
(6E)-6-[[[2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]hydrazo]methylidene]-1-cyclohexa-2,4-dienone	IC50	1030 nM
(6Z)-5-imino-6-(1H-indol-3-ylmethylene)-3-(methylsulfonyl)-5,6-dihydro-7H-[1,2,4]thiadiazolo[4,5-a]pyrimidin-7-one	IC50	1180 nM
3-(1-benzofuran-2-ylcarbonyl)-2-(3-chlorophenyl)-1-(5-methyl-1,2-oxazol-3-yl)-4-oxidanyl-2H-pyrrol-5-one	IC50	1190 nM
5,8-dimethyl-2-pyrrolidin-1-ylquinoline-3-carbonitrile	EC50	1210 nM
MLS001250005	EC50	1290 nM
2-[[[6-[(2,6-diketo-4,4-dimethyl-cyclohexylidene)methylamino]-2-pyridyl]amino]methylene]-5,5-dimethyl-cyclohexane-1,3-quinone	IC50	1310 nM
SMR000314559	EC50	1520 nM
(E)-2-Cyano-3-(9-methyl-4-oxo-2-phenoxy-4H-pyrido[1,2-a]pyrimidin-3-yl)-acrylamide	EC50	1580 nM
(2Z)-1,3-diketo-2-[(5-methyl-2-furyl)methylene]indane-5-carboxylic acid	IC50	1650 nM
MLS000722329	EC50	1660 nM
4-[(5-thiophen-2-yl-2-thiophenyl)methylideneamino]phenol	IC50	1680 nM
cid_2851959	IC50	1840 nM
N-[2-(2-Amino-3-cyano-pyrrolo[2,3-b]quinoxalin-1-yl)-ethyl]-4-chloro-benzamide	EC50	2040 nM
3-[(E)-2-(4-chlorophenyl)ethenyl]imidazo[1,5-a]pyridine	EC50	2540 nM
2-[(4-fluorophenyl)carbamoylamino]-4-methyl-thiazole-5-carboxylic acid ethyl ester	EC50	2670 nM
6-chloro-3-[2-[4-[2,3-dihydro-1,4-benzodioxin-3-yl(oxo)methyl]-1-piperazinyl]-2-oxoethyl]-7-hydroxy-4-methyl-1-benzopyran-2-one	EC50	2900 nM
2-(4-methylphenyl)-1,3-benzoxazol-5-amine	EC50	2910 nM
2-Amino-1-benzo[1,3]dioxol-5-ylmethyl-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylic acid butylamide	EC50	3120 nM
SMR000306079	IC50	3160 nM
N-(5,6-dihydrobenzo[h]quinazolin-2-yl)-2-propan-2-ylsulfanyl-ethanamide	EC50	3480 nM
2-(4,5-dichloro-6-oxopyridazin-1-yl)-N-(5-methoxy-2-methyl-4-nitrophenyl)acetamide	IC50	3520 nM
[4-[2-(3,5-dimethoxyphenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-7-yl]piperazin-1-yl]-(furan-2-yl)methanone	EC50	3680 nM
10-[3-[bis(3-methylbutyl)amino]-2-hydroxypropyl]acridin-9-one	EC50	3740 nM
N-(2-methoxyethyl)-5-methyl-2-(4-methylphenyl)pyrazolo[1,5-a]pyrimidin-7-amine	EC50	3770 nM
MLS000779605	EC50	3850 nM
MLS000948043	EC50	3870 nM
(3Z)-2-(1,3-dihydrobenzimidazol-2-ylidene)-3-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)propanenitrile	EC50	3930 nM
3-(2-methoxy-6-(4-methoxyphenyl)pyridin-3-yl)-5-o-tolyl-1,2,4-oxadiazole	IC50	3970 nM
5-[[5-(2,5-dichlorophenyl)-1H-pyrrol-2-yl]methylidene]-1,3-diazinane-2,4,6-trione	EC50	4040 nM
MLS000704256	EC50	4050 nM
SMR000460976	EC50	4110 nM
ethyl (2E)-5-oxo-1-propyl-2-[(pyridin-3-ylcarbonyl)imino]-1,5-dihydro-2H-dipyrido[1,2-a:2’,3’-d]pyrimidine-3-carboxylate	EC50	4180 nM
(5Z)-2-(4-fluoroanilino)-5-(1H-indol-3-ylmethylene)-2-thiazolin-4-one	IC50	4260 nM
N-[2-[(3-cyano-6-methyl-2-quinolinyl)amino]ethyl]benzamide	EC50	4660 nM
(4E)-1-(3,4-dimethylphenyl)-4-[(6-nitro-1,3-benzodioxol-5-yl)methylene]pyrazolidine-3,5-quinone	IC50	4660 nM
SMR000281941	EC50	4890 nM
SMR000152022	EC50	4900 nM
MLS000537373	EC50	4980 nM
cid_839240	EC50	5080 nM
(7-chloro-4-quinolyl)-[(2-methylbenzylidene)amino]amine	IC50	5130 nM
cid_645132	EC50	5280 nM
4-Methyl-benzoic acid N’-acridin-9-yl-hydrazide	IC50	5380 nM

ChEMBL bioactivities

8 potent at pChembl≥5 of 16 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.25	Kd	5.663	nM	CHEMBL5653589
8.25	ED50	5.663	nM	CHEMBL5653589
7.14	Kd	72	nM	MOLIBRESIB
6.85	IC50	140	nM	MOLIBRESIB
5.37	AC50	4275	nM	CHEMBL1308521
5.20	AC50	6365	nM	CHEMBL1432742
5.13	Kd	7334	nM	CHEMBL3752910
5.13	ED50	7334	nM	CHEMBL3752910

PubChem BioAssay actives

4 with measured affinity, of 12 total; 3 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	2148628: Binding affinity to human KPNA2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0057	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	2179220: Binding affinity against KPNA2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0720	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148628: Binding affinity to human KPNA2 incubated for 45 mins by Kinobead based pull down assay	kd	7.3344	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	5
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance	3
Calcitriol	decreases expression, affects cotreatment	3
Cisplatin	affects reaction, decreases expression, affects expression	3
Estradiol	decreases phosphorylation, increases expression	3
Resveratrol	decreases expression	2
Fulvestrant	affects cotreatment, increases methylation, decreases expression	2
Fluorouracil	decreases expression, affects reaction	2
Hydrogen Peroxide	affects expression, affects localization	2
Ivermectin	affects localization, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression	2
Tunicamycin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
gossypol acetic acid	decreases expression	1
ferrous chloride	increases expression	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CD 437	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 11 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738406	Functional	PUBCHEM_BIOASSAY: Counterscreen for target specificity Measured in Cell-Free Homogeneous System Using Plate Reader - 2041-02_Inhibitor_Dose_DryPowder_Activity. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID22	PubChem BioAssay data set
CHEMBL4119014	Binding	Binding affinity to KPNA2 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7XW	Abcam Raji KPNA2 KO	Cancer cell line	Male
CVCL_B9YL	Abcam THP-1 KPNA2 KO	Cancer cell line	Male
CVCL_C7AD	Abcam PC-3 KPNA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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