NUP153

Summary

NUP153 (nucleoporin 153, HGNC:8062) is a protein-coding gene on chromosome 6p22.3, encoding Nuclear pore complex protein Nup153 (P49790). Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. It is a selective cancer dependency (DepMap: 63.9% of cell lines).

Nuclear pore complexes regulate the transport of macromolecules between the nucleus and cytoplasm. They are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. Nucleoporins are glycoproteins found in nuclear pores and contain characteristic pentapeptide XFXFG repeats as well as O-linked N-acetylglucosamine residues oriented towards the cytoplasm. The protein encoded by this gene has three distinct domains: a N-terminal region containing a pore targeting and an RNA-binding domain domain, a central region containing multiple zinc finger motifs, and a C-terminal region containing multiple XFXFG repeats. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 9972 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 271 total
• Cancer dependency (DepMap): dependent in 63.9% of screened cell lines
• MANE Select transcript: NM_005124

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8062
Approved symbol	NUP153
Name	nucleoporin 153
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	HNUP153
Ensembl gene	ENSG00000124789
Ensembl biotype	protein_coding
OMIM	603948
Entrez	9972

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 23 protein_coding

ENST00000262077, ENST00000537253, ENST00000613258, ENST00000874440, ENST00000874441, ENST00000874442, ENST00000874443, ENST00000874444, ENST00000874445, ENST00000874446, ENST00000874447, ENST00000912063, ENST00000912064, ENST00000912065, ENST00000912066, ENST00000912067, ENST00000912068, ENST00000912069, ENST00000912070, ENST00000940939, ENST00000940940, ENST00000940941, ENST00000940942

RefSeq mRNA: 3 — MANE Select: NM_005124 NM_001278209, NM_001278210, NM_005124

CCDS: CCDS4541, CCDS64359, CCDS75407

Canonical transcript exons

ENST00000262077 — 22 exons

Exon	Start	End
ENSE00000848135	17615037	17616181
ENSE00000848136	17616527	17616695
ENSE00000848137	17624561	17624833
ENSE00000848138	17625808	17626164
ENSE00000848139	17628655	17629539
ENSE00000848140	17632650	17632844
ENSE00000848141	17637153	17637770
ENSE00000848142	17639939	17640064
ENSE00000848143	17646067	17646154
ENSE00000848144	17647807	17647905
ENSE00000848145	17649163	17649300
ENSE00000848146	17661653	17661779
ENSE00000848147	17662018	17662070
ENSE00000848148	17665239	17665385
ENSE00000848149	17668975	17669028
ENSE00000848150	17669293	17669337
ENSE00000848151	17669430	17669546
ENSE00000848152	17674905	17675033
ENSE00000848153	17675229	17675368
ENSE00000848154	17675522	17675770
ENSE00000848155	17688396	17688618
ENSE00001927997	17706277	17706925

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.6323 / max 292.0966, expressed in 1812 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72006	19.1055	1800
72005	12.2320	1748
72000	0.9710	573
72004	0.5277	252
71999	0.2981	128
72002	0.2082	81
72001	0.1703	57
72003	0.1195	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.77	gold quality
esophagus squamous epithelium	UBERON:0006920	95.16	gold quality
epithelium of nasopharynx	UBERON:0001951	94.93	gold quality
oocyte	CL:0000023	94.57	gold quality
cartilage tissue	UBERON:0002418	94.57	gold quality
tibia	UBERON:0000979	94.45	gold quality
germinal epithelium of ovary	UBERON:0001304	94.44	gold quality
squamous epithelium	UBERON:0006914	94.00	gold quality
choroid plexus epithelium	UBERON:0003911	93.83	gold quality
amniotic fluid	UBERON:0000173	93.50	gold quality
cervix squamous epithelium	UBERON:0006922	92.91	gold quality
epithelium of esophagus	UBERON:0001976	92.87	gold quality
upper leg skin	UBERON:0004262	92.49	gold quality
parietal pleura	UBERON:0002400	92.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.14	gold quality
visceral pleura	UBERON:0002401	91.70	gold quality
pleura	UBERON:0000977	91.66	gold quality
gingival epithelium	UBERON:0001949	91.62	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.29	gold quality
biceps brachii	UBERON:0001507	91.24	gold quality
skin of hip	UBERON:0001554	91.14	gold quality
epithelium of mammary gland	UBERON:0003244	91.13	gold quality
lower lobe of lung	UBERON:0008949	91.04	gold quality
cauda epididymis	UBERON:0004360	90.96	gold quality
mammary duct	UBERON:0001765	90.90	gold quality
sperm	CL:0000019	90.86	gold quality
tibialis anterior	UBERON:0001385	90.86	gold quality
ventricular zone	UBERON:0003053	90.72	gold quality
gingiva	UBERON:0001828	90.65	gold quality
palpebral conjunctiva	UBERON:0001812	90.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting NUP153, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
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-4668-3P	100.00	68.74	2635
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3143	99.93	71.96	3104

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 63.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Relocation of cellular proteins and inhibition of nuclear import in Hela cells during rhinovirus type 14 infection correlated with the degradation of Nup153 (PMID:12163599)
• Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. (PMID:12191473)
• Nup153 and Nup98 have distinct domains to mediate transcription-dependent mobility (PMID:14718558)
• nuclear import of the transcription factor PU.1 occurs via RanGTP-stimulated binding to Nup153 (PMID:15632149)
• in vitro-translated Nup153 coimmunoprecipitate HIV-1 Vpr; Nup153 shares a unique N-terminal domain with Nup124 that is absolutely essential for Tf1 transposition (PMID:15659641)
• MSL complex interacts with components of the nuclear pore, in particular Mtor/TPR and Nup153. Knockdown of Mtor or Nup153 results in loss of the typical MSL X-chromosomal staining and dosage compensation in Drosophila male cells but not in female cells. (PMID:16543150)
• Nup153 zinc fingers bound GDP and GTP forms of Ran with similar affinities, indicating that this interaction is not influenced by a nucleotide-dependent conformational switch (PMID:17426026)
• Although full-length Nup1p or Nup153 does not complement Nup124p, the functionality of their conserved domains with reference to Tf1 activity suggests that these three proteins evolved from a common ancestor. (PMID:17615301)
• study found binding interactions with karyopherin-beta1 caused FG domains of nucleoporin Nup153 to collapse into compact molecular conformations; reversible collapse of the FG domains may play an important role in regulating nucleocytoplasmic transport (PMID:17916694)
• The formation of high molecular mass complexes containing importin-alpha, Nup153 and Nup88 is increased upon oxidant treatment. (PMID:18068677)
• FG-rich region of Nup153 was required to rescue defects in late mitosis (PMID:19158386)
• HIV-1 integrase binds directly to nucleoporin NUP153 to mediate active nuclear import. (PMID:19369352)
• Nup153 levels regulate the localization of Mad1 during the metaphase/anaphase transition thereby affecting its phoshorylation status and in turn spindle checkpoint activity and mitotic exit. (PMID:21327106)
• NUP153 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• results suggest that capsid, likely by the qualities of its uncoating, determines whether HIV-1 requires cellular NUP153 for PIC nuclear import (PMID:21593146)
• Data suggest NUP153 plays a crucial role in the nuclear localization of the DICER1 protein. (PMID:21858095)
• The N-terminal domain of Nup153 and its C terminus associate with the Ig-fold domain of A- and B-type lamins. (PMID:21983083)
• Data show that the C-terminal part of NUP153 is required for effective 53BP1 nuclear import, and that 53BP1 is imported to the nucleus through the NUP153-importin-beta interplay. (PMID:22075984)
• A significant association of a polymorphic marker (rs2328136) near the NUP153 gene (which produces a 153 kDa nucleoporin) was obtained (PMID:22118420)
• human nucleoporin 153 (NUP153) has a role in repair of DSBs and in the activation of DNA damage checkpoints. (PMID:22249246)
• Nup153 binds to importin alpha (PMID:22510057)
• The Nup153 binds to both SENP1 and SENP2 and does so by interacting with the unique N-terminal domain of Nup153 as well as a specific region within the C-terminal FG-rich region. (PMID:22688647)
• analysis of the Nup153-Nup50 protein interface and its role in nuclear import (PMID:23007389)
• The roles of NUP153 and nup98 in the integration and replication of HIV-1 in human Jurkat lymphocytes are reported. (PMID:23523133)
• a subset of lentiviral CA proteins directly engage FG-motifs present on NUP153 to affect viral nuclear import. (PMID:24130490)
• A hydrophobic patch 65LRLFV69 within the zinc-binding domain is essential for the nuclear import and localization of HPV8 E7 via hydrophobic interactions with Nup62 and Nup153. (PMID:24418548)
• These data reveal an emergent Kap-centric barrier mechanism that may underlie mechanistic and kinetic control in the nuclear pore complex. (PMID:24739174)
• NUP153 and CPSF6 have overlapping binding sites, but each makes unique capsid monomers (CA) interactions. Multiple ligands share an overlapping interface in HIV-1 capsid that is lost upon viral disassembly. (PMID:25356722)
• The data presented here suggest that BGLF4 interferes with the normal functions of Nup62 and Nup153 and preferentially helps the nuclear import of viral proteins for viral DNA replication and assembly. (PMID:25410863)
• Our data indicate a central function of Nup153 in the organization of the nucleus, not only at the periphery, but throughout the entire nuclear interior. (PMID:25485891)
• Study assessed the extent of collapse of a Nup153 fragment in molecular dynamics simulations and compared the results to single molecule FRET and small-angle X-ray scattering experiments of this peptide (PMID:26030189)
• Nucleoporin Nup153 is required for NPC assembly during interphase but not during mitotic exit. It functions in interphasic NPC formation by binding directly to the inner nuclear membrane via an N-terminal amphipathic helix. (PMID:26051542)
• Nup153 is an epigenetic regulator which, upon altered NO signalling, mediates the activation of genes potentially associated with early dystrophic cardiac remodelling. (PMID:28513807)
• Despite the requirement of all three nucleoporins for accurate NHEJ, only Nup153 is needed for proper nuclear import of 53BP1 and SENP1-dependent sumoylation of 53BP1. Our data support the role of Nup153 as an important regulator of 53BP1 activity and efficient NHEJ. (PMID:28576968)
• results further highlight the antagonistic relationship between 53BP1 and BRCA1, and place Nup153 and Nup50 in a molecular pathway that regulates 53BP1 function by counteracting BRCA1-mediated events. (PMID:28751496)
• Seh1 is not required for the association of the Nup107 complex with mitotic chromosomes, but it is essential for the association of both the GATOR2 complex and nucleoporin Nup153 with mitotic chromosomes. (PMID:29618633)
• Nup153 is essential for the HIV-1 nuclear import in nondividing cells, and CPSF6 is important for HIV-1 integration. (PMID:29997211)
• Nup153 effectively assembled Nup98, Nup62 and Pom121 of the nuclear pore complex at the end of the mitosis. (PMID:30821042)
• Viral protein X unlocks the nuclear pore complex through a human Nup153-dependent pathway to promote nuclear translocation of the lentiviral genome. (PMID:31913756)
• NUP153 promotes HCC cells proliferation via c-Myc-mediated downregulation of P15[INK4b]. (PMID:35288064)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup153	ENSDARG00000099972
mus_musculus	Nup153	ENSMUSG00000021374
rattus_norvegicus	Nup153	ENSRNOG00000001456
drosophila_melanogaster	Nup153	FBGN0061200

Paralogs (6): NUP214 (ENSG00000126883), POM121L2 (ENSG00000158553), NPAP1 (ENSG00000185823), POM121 (ENSG00000196313), POM121L12 (ENSG00000221900), POM121C (ENSG00000272391)

Protein

Protein identifiers

Nuclear pore complex protein Nup153 — P49790 (reviewed: P49790)

Alternative names: 153 kDa nucleoporin, Nucleoporin Nup153

All UniProt accessions (1): P49790

UniProt curated annotations — full annotation on UniProt →

Function. Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC). (Microbial infection) Interacts with HIV-1 capsid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro). (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro).

Subunit / interactions. Part of the nuclear pore complex (NPC). Interacts with TPR (via coiled coil region); the interaction is direct and provides a link between the core structure and the TPR-containing nuclear basket of the nuclear pore complex (NPC). Interacts with HIKESHI. Interacts with SENP2. Interacts with XPO5. Interacts with RAN; the interaction occurs in a GTP- and GDP-independent manner. Interacts with MCM3AP isoform GANP; this interaction is required for GANP localization at the nuclear pore complex. Interacts with MAPK1. (Microbial infection) Interacts (via C-terminus) with HIV-1 capsid protein p24 (CA) (via N-terminus). (Microbial infection) Interacts with HIV-1 integrase; this interaction might play a role in nuclear import of HIV pre-integration complex. (Microbial infection) Interacts with hepatitis B virus capsid protein; this interaction probably plays a role in nuclear import of HBV genome. (Microbial infection) Interacts with Epstein-barr virus BGLF4; this interaction allows BGLF4 nuclear entry. (Microbial infection) Interacts with HIV-2 virus protein vpx; this interaction might promote vpx nuclear entry.

Subcellular location. Nucleus. Nucleus membrane. Nuclear pore complex.

Post-translational modifications. Phosphorylated in interphase, hyperphosphorylated during mitosis. May play a role in the reversible disassembly of the nuclear pore complex during mitosis. Proteolytically degraded after poliovirus (PV) infection; degradation is partial and NCP- and TPR-binding domains withstand degradation. O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status.

Disease relevance. The variant p.Pro485Leu has been identified in a patient with spermatogenic failure. This patient also carried a homozygous loss-of-function variant affecting a splice site in the NUP210L gene, thought to be the cause of the disease. As NUP210L knockout male mice are fertile, it has been proposed that the increased phenotypic severity associated with NUP210L loss in the patient was due to the presence of the additional NUP153 variant. However, interspecies divergence in the nuclear pore function of NUP210L in round spermatids cannot be ruled out.

Cofactor. Binds at least 4 zinc ions per subunit.

Domain organisation. Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. (Microbial infection) FG repeats mediates interaction with HIV-1 capsid protein p24 (CA).

Similarity. Belongs to the NUP153 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49790-1	1	yes
P49790-2	2
P49790-3	3

RefSeq proteins (3): NP_001265138, NP_001265139, NP_005115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001876	Znf_RanBP2	Domain
IPR013913	Nup153_N	Domain
IPR018892	Retro-transposon_transp_CS	Conserved_site
IPR026054	Nucleoporin	Family
IPR036443	Znf_RanBP2_sf	Homologous_superfamily

Pfam: PF00641, PF08604, PF10599

UniProt features (137 total): modified residue 36, repeat 29, binding site 16, compositionally biased region 10, strand 9, sequence variant 8, region of interest 8, glycosylation site 6, sequence conflict 4, zinc finger region 4, splice variant 2, initiator methionine 1, chain 1, cross-link 1, mutagenesis site 1, helix 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4U0C	X-RAY DIFFRACTION	1.77
5TSX	X-RAY DIFFRACTION	1.9
6AYA	X-RAY DIFFRACTION	2.4
5TSV	X-RAY DIFFRACTION	2.5
8CKY	ELECTRON MICROSCOPY	2.6
9CNU	ELECTRON MICROSCOPY	2.99
4U0D	X-RAY DIFFRACTION	3
8CL0	ELECTRON MICROSCOPY	3.12
2EBQ	SOLUTION NMR
2EBR	SOLUTION NMR
2EBV	SOLUTION NMR
2GQE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49790-F1	43.86	0.07

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (16): 664; 667; 678; 681; 728; 731; 742; 745; 799; 802; 813; 816 …

Post-translational modifications (37): 891, 954, 1457, 1461, 1463, 353, 2, 102, 182, 185, 192, 203, 209, 240, 257, 297, 320, 330, 333, 334 …

Glycosylation sites (6): 534, 544, 908, 909, 1113, 1156

Mutagenesis-validated functional residues (1):

Position	Phenotype
1415	reduces binding to hiv-1 capsid protein p24 (ca).

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-180746	Nuclear import of Rev protein
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-1855170	IPs transport between nucleus and cytosol
R-HSA-1855196	IP3 and IP4 transport between cytosol and nucleus
R-HSA-1855229	IP6 and IP7 transport between cytosol and nucleus
R-HSA-191859	snRNP Assembly
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-6784531	tRNA processing in the nucleus
R-HSA-9609690	HCMV Early Events
R-HSA-9610379	HCMV Late Events
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 313 (showing top): E2F_Q4, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, AAGCCAT_MIR135A_MIR135B, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, AACYNNNNTTCCS_UNKNOWN, BROWNE_HCMV_INFECTION_16HR_UP, MODULE_352, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GNF2_MCM5, GOBP_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, ATGTTAA_MIR302C, GOBP_NUCLEAR_PORE_ORGANIZATION

GO Biological Process (10): RNA export from nucleus (GO:0006405), protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), symbiont entry into host cell (GO:0046718), negative regulation of RNA export from nucleus (GO:0046832), mRNA transport (GO:0051028), nuclear pore complex assembly (GO:0051292), viral penetration into host nucleus (GO:0075732), amyloid fibril formation (GO:1990000), protein transport (GO:0015031)

GO Molecular Function (9): DNA binding (GO:0003677), nuclear localization sequence binding (GO:0008139), zinc ion binding (GO:0008270), structural constituent of nuclear pore (GO:0017056), identical protein binding (GO:0042802), protein-membrane adaptor activity (GO:0043495), molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), nuclear periphery (GO:0034399), nuclear inclusion body (GO:0042405), host cell (GO:0043657), nuclear pore nuclear basket (GO:0044615), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
SUMO E3 ligases SUMOylate target proteins	2
Antimicrobial mechanism of IFN-stimulated genes	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Nuclear Envelope Breakdown	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nucleus	3
nuclear lumen	3
RNA transport	2
nuclear pore	2
protein-macromolecule adaptor activity	2
nuclear envelope	2
nuclear protein-containing complex	2
nuclear export	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
nuclear transport	1
viral life cycle	1
symbiont entry into host	1
RNA export from nucleus	1
negative regulation of nucleobase-containing compound transport	1
negative regulation of nucleocytoplasmic transport	1
regulation of RNA export from nucleus	1
nuclear pore organization	1
pore complex assembly	1
intracellular transport of virus	1
protein metabolic process	1
supramolecular fiber organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
nucleic acid binding	1
signal sequence receptor activity	1
transition metal ion binding	1
structural molecule activity	1
nucleocytoplasmic transport	1
protein binding	1
binding	1
cation binding	1
endomembrane system	1
organelle envelope	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

2506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP153	NUP50	Q9UKX7	996
NUP153	NUP98	P52948	994
NUP153	NUP62	P37198	989
NUP153	RGPD1	P0C839	981
NUP153	NUP107	P57740	976
NUP153	TPR	P12270	975
NUP153	NUP133	Q8WUM0	974
NUP153	NUP160	Q12769	973
NUP153	AHCTF1	Q8WYP5	971
NUP153	NUP88	Q99567	963
NUP153	NUP155	O75694	947
NUP153	NUP35	Q8NFH5	940
NUP153	SUN1	O94901	919
NUP153	NUTF2	P13662	907
NUP153	NUP93	Q8N1F7	899

IntAct

191 interactions, top by confidence:

A	B	Type	Score
STAG1	RAD21	psi-mi:“MI:0914”(association)	0.930
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
NUP153	KPNB1	psi-mi:“MI:0914”(association)	0.820
KPNB1	NUP153	psi-mi:“MI:0407”(direct interaction)	0.820
KPNB1	NUP153	psi-mi:“MI:0915”(physical association)	0.820
NXF1	NUP214	psi-mi:“MI:0914”(association)	0.810
DICER1	PRKRA	psi-mi:“MI:0914”(association)	0.800
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
KPNA2	NUP153	psi-mi:“MI:0914”(association)	0.790
RAN	NUP153	psi-mi:“MI:0914”(association)	0.790
NUP50	KPNA3	psi-mi:“MI:0914”(association)	0.780
NUP153	NXF1	psi-mi:“MI:0407”(direct interaction)	0.760
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PHF5A	SF3B1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640

BioGRID (372): NUP153 (Affinity Capture-MS), NUP153 (Co-fractionation), NUP153 (Affinity Capture-MS), NUP153 (Reconstituted Complex), NUP62 (Affinity Capture-Western), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Affinity Capture-MS), NUP153 (Co-fractionation), NUP153 (Co-fractionation)

ESM2 similar proteins: A0JME2, A5H447, A6NF01, A8CG34, E9Q3G8, F4ID16, G0SDP9, G5E8Z2, O08587, O15504, O88797, O95081, P20676, P49790, P49791, P52591, P52594, P98082, Q03173, Q0VA45, Q2TA45, Q4KLH5, Q5FVW4, Q5PRE5, Q5RB98, Q5SV85, Q5XGN1, Q5ZI22, Q5ZIE8, Q5ZM88, Q64028, Q640Z6, Q6P0U9, Q80WC7, Q86XN7, Q8CIC2, Q8K2K6, Q8K3Z9, Q8L7F7, Q8R080

Diamond homologs: A0A0B4K7J2, E9Q3G8, H2QII6, P49790, P49791, P49792, Q640Z6, Q9ERU9, Q9VXE6

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	NUP153	phosphorylation
MAPK3	unknown	NUP153	phosphorylation
SUN1	“up-regulates activity”	NUP153	binding
Gbeta	unknown	NUP153	phosphorylation
ERK1/2	unknown	NUP153	phosphorylation
NUP153	“form complex”	NPC	binding
TNPO1	“up-regulates activity”	NUP153	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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	14	29.6×	7e-15
Nuclear import of Rev protein	11	27.4×	2e-11
Transport of the SLBP independent Mature mRNA	11	26.6×	2e-11
Transport of Ribonucleoproteins into the Host Nucleus	10	26.4×	2e-10
Transport of the SLBP Dependant Mature mRNA	11	25.9×	2e-11
Rev-mediated nuclear export of HIV RNA	11	25.9×	2e-11
NEP/NS2 Interacts with the Cellular Export Machinery	10	25.6×	2e-10
IPs transport between nucleus and cytosol	8	22.6×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	8	39.1×	4e-09
RNA export from nucleus	6	34.2×	3e-06
nucleocytoplasmic transport	10	23.9×	4e-09
mRNA export from nucleus	12	21.6×	2e-10
alternative mRNA splicing, via spliceosome	5	20.6×	5e-04
poly(A)+ mRNA export from nucleus	5	20.6×	5e-04
protein import into nucleus	22	19.3×	3e-19
U2-type prespliceosome assembly	5	19.0×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	202
Likely benign	17
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

3158 predictions. Top by Δscore:

Variant	Effect	Δscore
6:17616525:ACC:A	donor_gain	1.0000
6:17616526:CCC:C	donor_gain	1.0000
6:17616526:CCCCA:C	donor_gain	1.0000
6:17624559:A:AC	donor_gain	1.0000
6:17624560:C:CC	donor_gain	1.0000
6:17628651:TTA:T	donor_loss	1.0000
6:17628652:TAC:T	donor_loss	1.0000
6:17628653:A:AC	donor_gain	1.0000
6:17628654:C:CC	donor_gain	1.0000
6:17628654:C:CG	donor_loss	1.0000
6:17628654:CCAG:C	donor_gain	1.0000
6:17632751:C:A	donor_gain	1.0000
6:17637692:A:AC	donor_gain	1.0000
6:17637768:AACC:A	acceptor_loss	1.0000
6:17637769:ACCT:A	acceptor_loss	1.0000
6:17639922:T:C	donor_gain	1.0000
6:17639933:TCTTA:T	donor_loss	1.0000
6:17639934:CTTAC:C	donor_loss	1.0000
6:17639935:TTA:T	donor_loss	1.0000
6:17639936:TA:T	donor_loss	1.0000
6:17639937:A:T	donor_loss	1.0000
6:17639967:T:TA	donor_gain	1.0000
6:17640045:CA:C	acceptor_gain	1.0000
6:17640047:C:CC	acceptor_gain	1.0000
6:17640061:TGAG:T	acceptor_gain	1.0000
6:17640065:C:CC	acceptor_gain	1.0000
6:17646061:ACTT:A	donor_loss	1.0000
6:17646062:CTT:C	donor_loss	1.0000
6:17646063:TTAC:T	donor_loss	1.0000
6:17646064:TA:T	donor_loss	1.0000

AlphaMissense

9573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:17688570:A:G	W54R	0.999
6:17688570:A:T	W54R	0.999
6:17632698:A:G	C871R	0.998
6:17632744:C:A	W855C	0.998
6:17632744:C:G	W855C	0.998
6:17669476:G:T	A308D	0.998
6:17669484:A:C	S305R	0.998
6:17669484:A:T	S305R	0.998
6:17669486:T:G	S305R	0.998
6:17688568:C:A	W54C	0.998
6:17688568:C:G	W54C	0.998
6:17632697:C:G	C871S	0.997
6:17632698:A:T	C871S	0.997
6:17632731:A:G	C860R	0.997
6:17632740:A:G	C857R	0.997
6:17669467:A:G	I311T	0.997
6:17669467:A:T	I311K	0.997
6:17669470:C:G	R310P	0.997
6:17688578:A:T	V51E	0.997
6:17632730:C:G	C860S	0.996
6:17632731:A:T	C860S	0.996
6:17675550:A:C	S185R	0.996
6:17675550:A:T	S185R	0.996
6:17675552:T:G	S185R	0.996
6:17688566:A:G	L55P	0.996
6:17616109:T:A	R1472S	0.995
6:17616109:T:G	R1472S	0.995
6:17632696:A:C	C871W	0.995
6:17632738:A:C	C857W	0.995
6:17632739:C:T	C857Y	0.995

dbSNP variants (sampled 300 via entrez): RS1000036664 (6:17671566 C>T), RS1000057117 (6:17685476 G>A,T), RS1000057574 (6:17634410 C>T), RS1000072659 (6:17694845 G>A), RS1000121392 (6:17693841 G>A,C), RS1000138365 (6:17656976 G>A), RS1000173662 (6:17618628 C>G,T), RS1000175476 (6:17694023 A>G), RS1000208557 (6:17656347 G>A), RS1000264048 (6:17650449 C>A,T), RS1000330326 (6:17677068 G>C), RS1000365444 (6:17683774 T>C), RS1000383836 (6:17688298 A>C,T), RS1000469138 (6:17652472 T>A,C), RS1000483277 (6:17682570 T>C)

Disease associations

OMIM: gene MIM:603948 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000175_15	Height	7.000000e-07
GCST001762_629	Obesity-related traits	3.000000e-06
GCST001762_841	Obesity-related traits	5.000000e-06
GCST012490_651	Femur bone mineral density x serum urate levels interaction	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression, increases expression	3
sodium arsenite	affects cotreatment, increases expression, increases abundance	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	decreases expression, increases expression	1
diethyl maleate	affects localization, affects reaction, increases O-linked glycosylation, increases phosphorylation	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
seocalcitol	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, affects reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects localization, affects reaction	1
2-palmitoylglycerol	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
ICG 001	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Irinotecan	decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Acetaminophen	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1ZD	Abcam HeLa NUP153 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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