IPO5

Summary

IPO5 (importin 5, HGNC:6402) is a protein-coding gene on chromosome 13q32.2, encoding Importin-5 (O00410). Functions in nuclear protein import as nuclear transport receptor. It is a selective cancer dependency (DepMap: 13.7% of cell lines).

Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex. The protein encoded by this gene is a member of the importin beta family.

Source: NCBI Gene 3843 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 13.7% of screened cell lines
• MANE Select transcript: NM_002271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6402
Approved symbol	IPO5
Name	importin 5
Location	13q32.2
Locus type	gene with protein product
Status	Approved
Aliases	IMB3, MGC2068, PSE1
Ensembl gene	ENSG00000065150
Ensembl biotype	protein_coding
OMIM	602008
Entrez	3843

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000261574, ENST00000357602, ENST00000403772, ENST00000421861, ENST00000460070, ENST00000463157, ENST00000468620, ENST00000469360, ENST00000470493, ENST00000471898, ENST00000473582, ENST00000475420, ENST00000479736, ENST00000480611, ENST00000480641, ENST00000481455, ENST00000481689, ENST00000482642, ENST00000485433, ENST00000489058, ENST00000490369, ENST00000490680, ENST00000491555, ENST00000493122, ENST00000493281, ENST00000493492, ENST00000496368, ENST00000497270, ENST00000631030, ENST00000651721, ENST00000929020, ENST00000929021, ENST00000929022

RefSeq mRNA: 1 — MANE Select: NM_002271 NM_002271

CCDS: CCDS31999

Canonical transcript exons

ENST00000651721 — 29 exons

Exon	Start	End
ENSE00001336273	97954119	97954198
ENSE00001423502	98021736	98024296
ENSE00001428174	97953675	97953716
ENSE00001600380	97990126	97990222
ENSE00001614773	97993105	97993225
ENSE00001633319	98002467	98002591
ENSE00001642749	97992892	97993014
ENSE00001681377	97990433	97990537
ENSE00001727981	98000539	98000645
ENSE00002717684	97989062	97989164
ENSE00003491057	98020992	98021133
ENSE00003501060	98002684	98002773
ENSE00003510961	98015530	98015641
ENSE00003512288	98009881	98010013
ENSE00003534721	97985421	97985613
ENSE00003542669	98018485	98018704
ENSE00003545132	98019581	98019809
ENSE00003572270	98008059	98008142
ENSE00003581847	97997531	97997618
ENSE00003593903	98014042	98014214
ENSE00003604182	97982503	97982583
ENSE00003639527	97969723	97969830
ENSE00003651776	98016729	98016851
ENSE00003658721	98002864	98003037
ENSE00003675919	98015726	98015781
ENSE00003676974	98010103	98010224
ENSE00003686142	98012246	98012342
ENSE00003686973	98006130	98006348
ENSE00003848682	97976693	97976786

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 126.5768 / max 2508.2501, expressed in 1820 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135746	118.0682	1819
135745	4.7395	1644
207080	1.3499	801
135744	1.2408	696
135748	0.4871	260
135749	0.3156	127
135742	0.1741	3
135750	0.1141	18
207081	0.0636	14
135743	0.0182	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.37	gold quality
left testis	UBERON:0004533	99.03	gold quality
male germ cell	CL:0000015	98.96	gold quality
right testis	UBERON:0004534	98.92	gold quality
testis	UBERON:0000473	98.24	gold quality
ventricular zone	UBERON:0003053	98.21	gold quality
embryo	UBERON:0000922	98.12	gold quality
cartilage tissue	UBERON:0002418	97.99	gold quality
ganglionic eminence	UBERON:0004023	97.91	gold quality
cortical plate	UBERON:0005343	97.85	gold quality
body of pancreas	UBERON:0001150	97.74	gold quality
gastrocnemius	UBERON:0001388	97.36	gold quality
muscle of leg	UBERON:0001383	97.30	gold quality
stromal cell of endometrium	CL:0002255	97.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.14	gold quality
islet of Langerhans	UBERON:0000006	97.06	gold quality
pancreas	UBERON:0001264	96.96	gold quality
muscle organ	UBERON:0001630	96.83	gold quality
skeletal muscle organ	UBERON:0014892	96.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.82	gold quality
left ovary	UBERON:0002119	96.66	gold quality
gluteal muscle	UBERON:0002000	96.64	gold quality
smooth muscle tissue	UBERON:0001135	96.48	gold quality
biceps brachii	UBERON:0001507	96.24	gold quality
skeletal muscle tissue	UBERON:0001134	96.23	gold quality
calcaneal tendon	UBERON:0003701	96.18	gold quality
colonic epithelium	UBERON:0000397	96.16	gold quality
ovary	UBERON:0000992	96.12	gold quality
adult organism	UBERON:0007023	96.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

161 targeting IPO5, 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-4262	100.00	73.26	3931
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
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-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9718	99.94	68.91	918

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 23)

• L1 major capsid protein of human papillomavirus type 11 interacts with Kap beta3 nuclear import receptors (PMID:12620808)
• The KPNB3 locus may contain a disease-causing variant for schizophrenia. (PMID:15364420)
• HPV16 L2 interacts via its NLSs with a network of karyopherins and can enter the nucleus via several import pathways mediated by Kapalpha(2)beta(1) heterodimers, Kapbeta(2), and Kapbeta(3). (PMID:15507604)
• The present work suggests that the combination of the KPNA3 gene and the KPNB3 gene may increase a genetic risk for schizophrenia. (PMID:16644122)
• RanBP5 acts as an import factor for the newly synthesized influenza A virus RNA-dependent-RNA polymerase by targeting the PB1-PA dimer to the nucleus. (PMID:17005651)
• Lack of association of the KPNB3 locus in schizophrenia. (PMID:18295457)
• HPV-16 E5 protein binds to karyopherin beta3. (PMID:18455505)
• These results suggest that karyopherin beta3 plays a crucial role in apo A-I secretion. (PMID:18562802)
• Impaired p53 binding to importin: a novel mechanism of cytoplasmic sequestration identified in oxaliplatin-resistant cells. (PMID:19581934)
• The results of this study suggested that abnormal expression and alternative splicing of the IPO5 gene may be involved in the pathophysiology of schizophrenia. (PMID:20542336)
• importin beta3 is essential for the nuclear import of RPL7. The import is mediated via the multifaceted basic amino acid clusters present in the NH(2)-region of RPL7, and is RanGTP-dependent (PMID:20828572)
• The N-terminal of influenza A virus PB1 mediates its binding to host RanBP5. (PMID:21562121)
• In case of L7, importin beta2 or importin beta3 are preferentially used by clusters with a high import efficiency. (PMID:23266416)
• IQGAP1 interacts with human importin-beta5 in HEK 293T cells. (PMID:24196961)
• Single nucleotide polymorphism in IPO5 gene is associated with Peripheral Arterial Disease. (PMID:26488411)
• importin-alpha5, which is a key regulator of interferon signaling following Ebola virus infection, as one putative target of miRNA. (PMID:27094387)
• Importins, Impbeta, Kapbeta2, Imp4, Imp5, Imp7, Imp9, and Impalpha, show the H3 tail binding more tightly than the H4 tail. The H3 tail binds Kapbeta2 and Imp5 with KD values of 77 and 57 nm, respectively, and binds the other five Importins more weakly. (PMID:27528606)
• The nuclear importin IPO5 was identified as a novel interacting protein of SMAD1. Overexpression of IPO5 in various cell lines specifically increases nuclear localization of BMP receptor-activated SMADs (R-SMADs) confirming a functional relationship between IPO5 and BMP but not TGF-beta R-SMADs. (PMID:27703004)
• Results indicate that the interaction between FLIL33 and IPO5 is localized to a specific segment of the FLIL33 protein, is not required for nuclear localization of FLIL33, and protects FLIL33 from proteasome-dependent degradation. (PMID:29127199)
• IPO5 is an oncogene involved in CRC cell proliferation and migration. This highlights the significance of IPO5 in 5-fluorouracil-resistant CRC cells. The oncogenic function of IPO5 was mediated by promoting RAS signalling by increasing the nuclear translocation of RASAL2 (PMID:31288861)
• DDX56 inhibits type I interferon by disrupting assembly of IRF3-IPO5 to inhibit IRF3 nucleus import. (PMID:31340999)
• X-ray Structure of the Human Karyopherin RanBP5, an Essential Factor for Influenza Polymerase Nuclear Trafficking. (PMID:32222384)
• IPO5 promotes malignant progression of esophageal cancer through activating MMP7. (PMID:32373960)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kpnb3	ENSDARG00000040245
mus_musculus	Ipo5	ENSMUSG00000030662
rattus_norvegicus	Ipo5	ENSRNOG00000010989
drosophila_melanogaster	Karybeta3	FBGN0087013
caenorhabditis_elegans		WBGENE00002076
caenorhabditis_elegans	imb-3	WBGENE00002077

Paralogs (5): TNPO1 (ENSG00000083312), TNPO2 (ENSG00000105576), KPNB1 (ENSG00000108424), RANBP6 (ENSG00000137040), IPO4 (ENSG00000196497)

Protein

Protein identifiers

Importin-5 — O00410 (reviewed: O00410)

Alternative names: Importin subunit beta-3, Karyopherin beta-3, Ran-binding protein 5

All UniProt accessions (18): O00410, A0A0D9SG25, C9J583, C9J875, C9JQT6, C9JXE0, C9JZ53, C9JZD8, E7EQT5, E7ESZ1, E7ETV3, E7ETV8, E7EV12, E7EWK4, E7EX05, F8WF30, H0Y3V4, H0Y8C6

UniProt curated annotations — full annotation on UniProt →

Function. Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin 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 the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. 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. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. Binds to CPEB3 and mediates its nuclear import following neuronal stimulation. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev.

Subunit / interactions. Interacts with RPS7 and RPL5. Interacts with RPL23A (via BIB domain). Interacts with H2A, H2B, H3 and H4 histones. Interacts with CPEB3; this mediates CPEB3 nuclear import following neuronal stimulation which enhances the interaction in a RAN-regulated manner. Interacts with AIFM2; this interaction likely mediates the translocation of AIFM2 into the nucleus upon oxidative stress. Interacts with STX3 (isoform 3). Interacts with SRP19. (Microbial infection) Interacts with HIV-1 Rev.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Similarity. Belongs to the importin beta family. Importin beta-3 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O00410-1	1	yes
O00410-2	2
O00410-3	3

RefSeq proteins (1): NP_002262* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000357	HEAT	Repeat
IPR001494	Importin-beta_N	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR034085	TOG	Domain
IPR040122	Importin_beta	Family
IPR040928	Importin_rep_5	Repeat
IPR041389	Importin_rep_6	Repeat
IPR041653	Importin_rep_4	Repeat
IPR057672	TPR_IPO4/5	Domain
IPR058584	IMB1_TNPO1-like_TPR	Domain

Pfam: PF02985, PF13513, PF18808, PF18816, PF18829, PF25574, PF25780

UniProt features (134 total): helix 73, repeat 24, turn 12, strand 10, sequence variant 5, modified residue 2, splice variant 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6XTE	X-RAY DIFFRACTION	2.27
6XU2	X-RAY DIFFRACTION	2.83
9IM6	ELECTRON MICROSCOPY	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00410-F1	92.12	0.81

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 (2): 2, 827

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-192905	vRNP Assembly
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-5663205	Infectious disease
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 308 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GCM_MAP4K4, GCM_GSPT1, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOMF_GTPASE_BINDING, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_NUCLEAR_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (9): cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), protein import into nucleus (GO:0006606), NLS-bearing protein import into nucleus (GO:0006607), ribosomal protein import into nucleus (GO:0006610), positive regulation of protein import into nucleus (GO:0042307), negative regulation of cell cycle (GO:0045786), cellular response to amino acid stimulus (GO:0071230), intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (6): RNA binding (GO:0003723), GTPase inhibitor activity (GO:0005095), nuclear localization sequence binding (GO:0008139), small GTPase binding (GO:0031267), nuclear import signal receptor activity (GO:0061608), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Influenza Viral RNA Transcription and Replication	1
Viral Infection Pathways	1
Influenza Infection	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein import into nucleus	3
import into nucleus	2
intracellular protein localization	2
intracellular membrane-bounded organelle	2
nuclear envelope	2
nuclear lumen	2
cytoplasm	2
positive regulation of cytokine production	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
intracellular protein transport	1
protein localization to nucleus	1
establishment of protein localization to organelle	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
response to amino acid	1
cellular response to acid chemical	1
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
nucleic acid binding	1
GTPase activity	1
enzyme inhibitor activity	1
GTPase regulator activity	1
signal sequence receptor activity	1
GTPase binding	1
nucleocytoplasmic carrier activity	1
binding	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
endomembrane system	1
nucleus	1

Protein interactions and networks

STRING

2758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IPO5	IPO11	Q9UI26	903
IPO5	RPL23A	P29316	828
IPO5	IRF3	Q14653	819
IPO5	RAN	P17080	777
IPO5	XPO1	O14980	762
IPO5	KPNA3	O00505	737
IPO5	RPL12	P30050	737
IPO5	IPO13	O94829	722
IPO5	IPO7	O95373	718
IPO5	LRRC70	Q7Z2Q7	712
IPO5	SENP3	Q9H4L4	694
IPO5	KPNA2	P52292	676
IPO5	MAGOH	P50606	674
IPO5	IPO9	Q96P70	674
IPO5	MAGOHB	Q96A72	672

IntAct

250 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GABARAPL2	IPO5	psi-mi:“MI:0407”(direct interaction)	0.690
IPO5	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.690
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
IPO5	GABARAP	psi-mi:“MI:0407”(direct interaction)	0.590
GABARAPL1	IPO5	psi-mi:“MI:0407”(direct interaction)	0.590
IPO5	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.590
IPO5	GABARAP	psi-mi:“MI:0915”(physical association)	0.590
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
GABARAPL1	IPO5	psi-mi:“MI:0914”(association)	0.590
IPO5	PA	psi-mi:“MI:0915”(physical association)	0.550
PA	IPO5	psi-mi:“MI:0914”(association)	0.550
IPO5	MAP1LC3B	psi-mi:“MI:0407”(direct interaction)	0.540
MAP1LC3C	IPO5	psi-mi:“MI:0407”(direct interaction)	0.540
IPO5	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.540
MAP1LC3C	IPO5	psi-mi:“MI:0915”(physical association)	0.540
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
NOL9	IPO5	psi-mi:“MI:0914”(association)	0.530
AVPI1	UNC119B	psi-mi:“MI:0914”(association)	0.530
NOL7	IPO5	psi-mi:“MI:0914”(association)	0.530
NOP16	IPO5	psi-mi:“MI:0914”(association)	0.530
IPO5	SLC27A2	psi-mi:“MI:0914”(association)	0.530

BioGRID (544): IPO5 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), IPO5 (Reconstituted Complex), IPO5 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), CAND1 (Co-fractionation), CLTC (Co-fractionation), CSE1L (Co-fractionation), DCAF13 (Co-fractionation), DDX56 (Co-fractionation), FBL (Co-fractionation), HSD17B12 (Co-fractionation), IPO5 (Co-fractionation), IPO5 (Co-fractionation)

ESM2 similar proteins: A5D785, A5WW24, O00410, O04375, O04376, O15397, O35638, O46563, O60518, O95373, Q08AM6, Q16401, Q499Y0, Q569Z2, Q5IFJ8, Q5R9G4, Q5R9J2, Q5ZLT0, Q5ZMR9, Q68F38, Q6GMY9, Q704U0, Q7PC79, Q7TMY7, Q802D3, Q8AY73, Q8BIV3, Q8BKC5, Q8GUL2, Q8K2V6, Q8N3U4, Q8VI75, Q8WVM7, Q91YE6, Q924C1, Q96P70, Q99NF8, Q9C0E2, Q9D3E6, Q9DGN0

Diamond homologs: O00410, O14089, O60518, O74476, P32337, Q8BIV3, Q8BKC5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IPO5	“up-regulates activity”	DSCAM	relocalization
IPO5	“up-regulates activity”	DSCAML1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 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
Major pathway of rRNA processing in the nucleolus and cytosol	11	6.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	6	13.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000136759 (13:97961340 C>T), RS1000143187 (13:97987420 A>G), RS1000148522 (13:98001426 A>G), RS1000152424 (13:97994243 G>A,T), RS1000207643 (13:97951947 A>G), RS1000287446 (13:97995375 G>C), RS1000367841 (13:98021886 T>G), RS1000368746 (13:97959959 G>A,T), RS1000402279 (13:97961563 A>G), RS1000445122 (13:97989589 T>A,C), RS1000511660 (13:97987739 A>G), RS1000513847 (13:97996586 G>A), RS1000543573 (13:98004701 C>A,T), RS1000615588 (13:97956006 C>T), RS1000618565 (13:98010979 C>G)

Disease associations

OMIM: gene MIM:602008 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002361_31	Smooth-surface caries	9.000000e-07
GCST002711_10	Sleep duration	3.000000e-06
GCST003154_4	Peripheral artery disease	7.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295647 (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
8.35	Kd	4.449	nM	CHEMBL3752910
8.35	ED50	4.449	nM	CHEMBL3752910
6.47	Kd	341.7	nM	CHEMBL5653589
6.47	ED50	341.7	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 19 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	2148596: Binding affinity to human IPO5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0044	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148596: Binding affinity to human IPO5 incubated for 45 mins by Kinobead based pull down assay	kd	0.3417	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	7
trichostatin A	decreases expression, affects cotreatment	3
Tretinoin	decreases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
tamibarotene	affects expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118723	Binding	Binding affinity to IPO5 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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