IPO7

Summary

IPO7 (importin 7, HGNC:9852) is a protein-coding gene on chromosome 11p15.4, encoding Importin-7 (O95373). Functions in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. It is a common-essential gene (DepMap: required in 98.0% of cancer cell lines).

The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. Similar to importin-beta, this protein prevents the activation of Ran’s GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP, and also binds directly to nuclear pore complexes where it competes for binding sites with importin-beta and transportin. This protein has a Ran-dependent transport cycle and it can cross the nuclear envelope rapidly and in both directions. At least four importin beta-like transport receptors, namely importin beta itself, transportin, RanBP5 and RanBP7, directly bind and import ribosomal proteins.

Source: NCBI Gene 10527 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 125 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_006391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9852
Approved symbol	IPO7
Name	importin 7
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	Imp7
Ensembl gene	ENSG00000205339
Ensembl biotype	protein_coding
OMIM	605586
Entrez	10527

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000379719, ENST00000527431, ENST00000528833, ENST00000530037, ENST00000531235, ENST00000533233, ENST00000533680, ENST00000630083, ENST00000877280, ENST00000877281, ENST00000970585

RefSeq mRNA: 1 — MANE Select: NM_006391 NM_006391

CCDS: CCDS31425

Canonical transcript exons

ENST00000379719 — 25 exons

Exon	Start	End
ENSE00001482246	9445097	9448127
ENSE00001482247	9442081	9442197
ENSE00001482248	9440455	9440661
ENSE00001482250	9438080	9438285
ENSE00001482252	9437754	9437974
ENSE00001482254	9434934	9435031
ENSE00001482255	9433721	9433846
ENSE00001482256	9433570	9433636
ENSE00001482258	9430875	9431003
ENSE00001482259	9429674	9429834
ENSE00001482260	9429031	9429196
ENSE00001482262	9428540	9428629
ENSE00001482263	9425146	9425262
ENSE00001482270	9423777	9423876
ENSE00001482271	9423006	9423140
ENSE00001482273	9420614	9420698
ENSE00001482274	9420411	9420505
ENSE00001482276	9417059	9417148
ENSE00001482277	9414255	9414411
ENSE00001482279	9409928	9410086
ENSE00001506345	9403290	9403371
ENSE00001744447	9436271	9436366
ENSE00002161415	9384652	9384847
ENSE00003660901	9424914	9424990
ENSE00003677130	9408486	9408639

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 143.3480 / max 745.4503, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112971	132.3076	1827
112968	3.8562	1616
112969	2.8068	1479
112970	2.2822	1393
112974	1.3075	735
112975	0.7877	372

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	99.04	gold quality
cartilage tissue	UBERON:0002418	98.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.33	gold quality
biceps brachii	UBERON:0001507	98.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.12	gold quality
lower lobe of lung	UBERON:0008949	98.09	gold quality
triceps brachii	UBERON:0001509	98.08	gold quality
deltoid	UBERON:0001476	98.00	gold quality
cauda epididymis	UBERON:0004360	97.86	gold quality
skeletal muscle tissue	UBERON:0001134	97.59	gold quality
caput epididymis	UBERON:0004358	97.51	gold quality
tibialis anterior	UBERON:0001385	97.47	gold quality
body of tongue	UBERON:0011876	97.39	gold quality
diaphragm	UBERON:0001103	97.24	gold quality
corpus epididymis	UBERON:0004359	97.24	gold quality
pericardium	UBERON:0002407	97.17	gold quality
cortical plate	UBERON:0005343	97.09	gold quality
vastus lateralis	UBERON:0001379	96.99	gold quality
tongue	UBERON:0001723	96.99	gold quality
pigmented layer of retina	UBERON:0001782	96.99	gold quality
muscle tissue	UBERON:0002385	96.99	gold quality
quadriceps femoris	UBERON:0001377	96.92	gold quality
ventricular zone	UBERON:0003053	96.92	gold quality
esophagus squamous epithelium	UBERON:0006920	96.80	gold quality
mammalian vulva	UBERON:0000997	96.76	gold quality
muscle organ	UBERON:0001630	96.74	gold quality
germinal epithelium of ovary	UBERON:0001304	96.72	gold quality
islet of Langerhans	UBERON:0000006	96.71	gold quality
gastrocnemius	UBERON:0001388	96.71	gold quality
ganglionic eminence	UBERON:0004023	96.59	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.57
E-CURD-112	yes	8.66
E-MTAB-3929	no	157.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TP53

miRNA regulators (miRDB)

221 targeting IPO7, 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-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
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-6077	99.99	68.04	2299
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-381-3P	99.93	71.87	2854

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 20)

• role of IMP7 in nuclear transport of H1 histones (PMID:12080050)
• Nuclear import of HIV-1 intracellular reverse transcription is mediated by IPO7. (PMID:12853482)
• These results identify EZI as a novel cargo protein for importin-7 and demonstrate a nucleocytoplasmic shuttling mechanism that is mediated by importin-7-dependent nuclear localization and CRM1-independent nuclear export. (PMID:17848547)
• When the import assay was performed with a low concentration of each importin- subtype, NPI2/importin-7 elicited more efficient transport activity of the human herpesvirus 6 U69 protein (PMID:18003734)
• TGF-beta-induced and basal state spontaneous nuclear import of Smad4 require importin 7 and 8. (PMID:18519565)
• Although imp7 may not be essential for HIV-1 infection, our results suggest that imp7 facilitates nuclear trafficking of DNA and that HIV-1 exploits imp7 to maximize nuclear import of its DNA genome. (PMID:19193229)
• Data show that ARHI could compete for Ran-importin binding and induce disruption of importin-binding to cargo proteins, including STAT3. (PMID:19435463)
• importins 4 and 7 accomplish nuclear import of HIF-1alpha more efficiently than the classical importin alpha/beta NLS receptor (PMID:19788888)
• essential for Egr-1 nuclear translocation (PMID:21419860)
• Importin 7 (IPO7)is regulated positively by c-Myc and negatively by p53. (PMID:22284678)
• imp7 is a part of an intrinsic pathway that promotes nuclear import of exogenous and endogenous DNA in mammalian cells. (PMID:23067392)
• Importin 7 contributes to the regulation of androgen receptor import by restraining import until androgen is detected in the cytoplasm. (PMID:24100013)
• Importin 7 as a soluble nuclear transport factor that is required for efficient import of the protein component of human telomerase. (PMID:24586428)
• Depletion of IPO7 by IPO7 siRNA reduced nuclear accumulation of GLI1. In addition, FOXM1 induced nuclear import of GLI1 by promoting IPO7 expression. (PMID:26085085)
• AKT and 14-3-3 proteins down-regulate the activity of several BCR-associated components, including BTK, BLNK and SYK and also inhibit SYK’s interaction with Importin 7 (PMID:27381982)
• 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)
• Pediatric ependymoma: GNAO1, ASAH1, IMMT and IPO7 protein expression and 5-year prognosis correlation. (PMID:31505435)
• The sequence [EKRKI(E/R)(K/L/R/S/T)] is a nuclear localization signal for importin 7 binding (NLS7). (PMID:33482249)
• IPO7 promotes pancreatic cancer progression via regulating ERBB pathway. (PMID:35588577)
• Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma. (PMID:38650127)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ipo7	ENSDARG00000035751
mus_musculus	Ipo7	ENSMUSG00000066232
rattus_norvegicus	Ipo7	ENSRNOG00000010427
drosophila_melanogaster	msk	FBGN0026252

Paralogs (4): IPO11 (ENSG00000086200), CSE1L (ENSG00000124207), IPO8 (ENSG00000133704), IPO9 (ENSG00000198700)

Protein

Protein identifiers

Importin-7 — O95373 (reviewed: O95373)

Alternative names: Ran-binding protein 7

All UniProt accessions (3): O95373, E9PLB2, E9PLJ0

UniProt curated annotations — full annotation on UniProt →

Function. Functions in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, is thought to serve itself as receptor for nuclear localization signals (NLS) and to promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to 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 autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. In association with KPNB1 mediates the nuclear import of H1 histone and the Ran-binding site of IPO7 is not required but synergizes with that of KPNB1 in importin/substrate complex dissociation. Promotes odontoblast differentiation via promoting nuclear translocation of DLX3, KLF4, SMAD2, thereby facilitating the transcription of target genes that play a role in odontoblast differentiation. Facilitates BMP4-induced translocation of SMAD1 to the nucleus and recruitment to the MSX1 gene promoter, thereby promotes the expression of the odontogenic regulator MSX1 in dental mesenchymal cells. Also promotes odontoblast differentiation by facilitating the nuclear translocation of HDAC6 and subsequent repression of RUNX2 expression. Inhibits osteoblast differentiation by inhibiting nuclear translocation of RUNX2 and therefore inhibition of RUNX2 target gene transcription. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. (Microbial infection) Mediates the nuclear import of HIV-1 reverse transcription complex (RTC) integrase. Binds and mediates the nuclear import of HIV-1 Rev.

Subunit / interactions. Forms a heterodimer with KPNB1. Interacts with histone H1. Interacts with H2A, H2B, H3 and H4 histones. Interacts with SNUPN and XPO1. Interacts with RPS7 and RPL5. Interacts with RPL23A (via BIB domain). Binds directly to nuclear pore complexes. Interacts with SMAD4 and NUP93; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling. Interacts with phosphorylated SMAD2; the interaction facilitates translocation of SMAD2 to the nucleus. Interacts with SRP19. Interacts with RUNX2; the interaction inhibits RUNX2 nuclear translocation in osteoblasts. Interacts with HDAC6, DLX3 and KLF4; the interaction facilitates HDAC6, DLX3 and KLF4 nuclear translocation in dental papilla cells. (Microbial infection) Interacts with HIV-1 reverse transcription complex integrase and rev.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the importin beta family.

RefSeq proteins (1): NP_006382* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001494	Importin-beta_N	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR013713	XPO2_central	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR058669	TPR_IPO7/11-like	Domain

Pfam: PF03810, PF08506, PF25758

UniProt features (11 total): modified residue 5, chain 1, domain 1, mutagenesis site 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95373-F1	88.24	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.

Post-translational modifications (5): 1, 886, 898, 903, 1020

Mutagenesis-validated functional residues (1):

Position	Phenotype
61	lowered affinity for rangtp-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918432	Maturation of DENV proteins

MSigDB gene sets: 335 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, RNGTGGGC_UNKNOWN, E2F_Q4, GCM_MAP4K4, E2F_Q4_01, RRAGTTGT_UNKNOWN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EPITHELIUM_DEVELOPMENT, E2F4DP1_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_OSTEOBLAST_DIFFERENTIATION, CAFFAREL_RESPONSE_TO_THC_UP, MODULE_352, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (8): protein import into nucleus (GO:0006606), innate immune response (GO:0045087), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of cell cycle (GO:0045786), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of odontoblast differentiation (GO:1901331), intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (5): GTPase regulator activity (GO:0030695), small GTPase binding (GO:0031267), histone binding (GO:0042393), SMAD binding (GO:0046332), protein binding (GO:0005515)

GO Cellular Component (7): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Genome Translation and Replication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein localization to nucleus	2
intracellular protein localization	2
protein binding	2
intracellular protein transport	1
import into nucleus	1
establishment of protein localization to organelle	1
immune response	1
defense response to symbiont	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
regulation of protein localization to nucleus	1
positive regulation of protein localization	1
odontoblast differentiation	1
regulation of odontoblast differentiation	1
positive regulation of neuroepithelial cell differentiation	1
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
GTPase activity	1
nucleoside-triphosphatase regulator activity	1
GTPase binding	1
binding	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
nuclear protein-containing complex	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2669 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IPO7	IPO9	Q96P70	840
IPO7	TNPO2	O14787	805
IPO7	TNPO1	Q92973	800
IPO7	XPO1	O14980	790
IPO7	NUP153	P49790	780
IPO7	XPOT	O43592	767
IPO7	TNPO3	Q9Y5L0	766
IPO7	IPO13	O94829	735
IPO7	IPO4	Q8TEX9	734
IPO7	RANBP1	P43487	730
IPO7	IPO5	O00410	718
IPO7	KPNB1	Q14974	649
IPO7	XPO5	Q9HAV4	642
IPO7	H1-0	P07305	625
IPO7	NUP85	Q9BW27	623

IntAct

285 interactions, top by confidence:

A	B	Type	Score
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PA	IPO5	psi-mi:“MI:0914”(association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
FZD10	NRP1	psi-mi:“MI:0914”(association)	0.530
HP1BP3	IPO8	psi-mi:“MI:0914”(association)	0.530
CD274	TTI1	psi-mi:“MI:0914”(association)	0.530
ZNF354C	IPO8	psi-mi:“MI:0914”(association)	0.530
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZBTB38	IPO7	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ZNF577	IPO7	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (406): IPO7 (Affinity Capture-RNA), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Reconstituted Complex), IPO7 (Reconstituted Complex), RAN (Reconstituted Complex), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), IPO7 (Affinity Capture-MS)

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: A5WW24, O15397, O95373, Q7TMY7, Q9EPL8, F4IRR2, F4J738, Q55CX9, O59809, Q9ZPY7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 226 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
Rev-mediated nuclear export of HIV RNA	7	14.5×	2e-04
NEP/NS2 Interacts with the Cellular Export Machinery	6	13.6×	1e-03
Nuclear import of Rev protein	6	13.2×	1e-03
Transport of Ribonucleoproteins into the Host Nucleus	5	11.7×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein import into nucleus	11	8.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3928 predictions. Top by Δscore:

Variant	Effect	Δscore
11:9384843:ATGAA:A	donor_gain	1.0000
11:9384844:TGAA:T	donor_gain	1.0000
11:9384845:GAA:G	donor_gain	1.0000
11:9384845:GAAG:G	donor_gain	1.0000
11:9384846:AA:A	donor_gain	1.0000
11:9384846:AAG:A	donor_loss	1.0000
11:9384847:AG:A	donor_loss	1.0000
11:9384848:G:GG	donor_gain	1.0000
11:9384848:G:T	donor_loss	1.0000
11:9384853:G:GT	donor_gain	1.0000
11:9403284:TTGTA:T	acceptor_loss	1.0000
11:9403285:TGTA:T	acceptor_loss	1.0000
11:9403286:GTA:G	acceptor_loss	1.0000
11:9403287:TAGG:T	acceptor_loss	1.0000
11:9403288:A:AG	acceptor_gain	1.0000
11:9403288:AGG:A	acceptor_loss	1.0000
11:9403289:G:GG	acceptor_gain	1.0000
11:9408471:T:A	acceptor_gain	1.0000
11:9408481:TTTA:T	acceptor_loss	1.0000
11:9408484:A:AG	acceptor_gain	1.0000
11:9408484:AGGTG:A	acceptor_loss	1.0000
11:9408485:G:A	acceptor_loss	1.0000
11:9408485:G:GG	acceptor_gain	1.0000
11:9408485:GGT:G	acceptor_gain	1.0000
11:9408635:ATCAG:A	donor_gain	1.0000
11:9408636:TCAG:T	donor_gain	1.0000
11:9408637:CAGG:C	donor_loss	1.0000
11:9408640:G:GG	donor_gain	1.0000
11:9408641:T:G	donor_loss	1.0000
11:9409926:A:AG	acceptor_gain	1.0000

AlphaMissense

6943 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:9384792:T:C	L10P	1.000
11:9384840:T:C	L26P	1.000
11:9403371:G:C	G56R	1.000
11:9408486:G:A	G56D	1.000
11:9408498:T:C	L60P	1.000
11:9408500:A:G	K61E	1.000
11:9408501:A:T	K61I	1.000
11:9408502:A:C	K61N	1.000
11:9408502:A:T	K61N	1.000
11:9408521:T:A	W68R	1.000
11:9408521:T:C	W68R	1.000
11:9408523:G:C	W68C	1.000
11:9408523:G:T	W68C	1.000
11:9408594:G:C	R92P	1.000
11:9409936:T:C	L110P	1.000
11:9409983:T:A	W126R	1.000
11:9409983:T:C	W126R	1.000
11:9410046:G:A	G147R	1.000
11:9410046:G:C	G147R	1.000
11:9410071:T:C	L155P	1.000
11:9414388:A:G	K205E	1.000
11:9414390:G:C	K205N	1.000
11:9414390:G:T	K205N	1.000
11:9417104:T:A	W228R	1.000
11:9417104:T:C	W228R	1.000
11:9420456:T:A	W258R	1.000
11:9420456:T:C	W258R	1.000
11:9420470:G:C	K262N	1.000
11:9420470:G:T	K262N	1.000
11:9420471:T:A	W263R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003076 (11:9392252 G>A), RS1000039956 (11:9409521 A>G), RS1000152621 (11:9419414 G>A), RS1000193804 (11:9426908 C>T), RS1000204634 (11:9419168 A>G), RS1000209787 (11:9432792 G>A), RS1000283499 (11:9430782 C>A,T), RS1000367593 (11:9384648 C>G,T), RS1000372341 (11:9383831 C>G), RS1000379867 (11:9390920 C>T), RS1000417436 (11:9430571 G>A), RS1000451820 (11:9387912 C>T), RS1000544151 (11:9431672 T>A), RS1000570436 (11:9431843 C>T), RS1000647015 (11:9383400 A>G,T)

Disease associations

OMIM: gene MIM:605586 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006102_2	Interleukin-10 levels	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004750	interleukin 10 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066503 (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
7.74	Kd	18.1	nM	CHEMBL5653589
7.74	ED50	18.1	nM	CHEMBL5653589
6.55	Kd	280.3	nM	CHEMBL3752910
6.55	ED50	280.3	nM	CHEMBL3752910

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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148597: Binding affinity to human IPO7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0181	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148597: Binding affinity to human IPO7 incubated for 45 mins by Kinobead based pull down assay	kd	0.2803	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance	3
Cadmium Chloride	decreases expression, increases expression, decreases reaction, increases abundance, increases palmitoylation	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
sodium arsenite	decreases expression	2
bisphenol S	decreases methylation, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, affects cotreatment	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
benzo(e)pyrene	increases methylation	1
1-nitropyrene	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	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
CHEMBL5651639	Binding	Binding affinity to human IPO7 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)

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

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia