NUP62

Summary

NUP62 (nucleoporin 62, HGNC:8066) is a protein-coding gene on chromosome 19q13.33, encoding Nuclear pore glycoprotein p62 (P37198). Essential component of the nuclear pore complex. It is a selective cancer dependency (DepMap: 79.6% of cell lines).

The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform.

Source: NCBI Gene 23636 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial infantile bilateral striatal necrosis (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 31 total
• Phenotypes (HPO): 42
• Cancer dependency (DepMap): dependent in 79.6% of screened cell lines
• MANE Select transcript: NM_016553

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8066
Approved symbol	NUP62
Name	nucleoporin 62
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	p62, DKFZp547L134, IBSN, SNDI, MGC841, FLJ20822, FLJ43869
Ensembl gene	ENSG00000213024
Ensembl biotype	protein_coding
OMIM	605815
Entrez	23636

Gene structure

Transcript identifiers

Ensembl transcripts: 72 — 66 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000352066, ENST00000422090, ENST00000593652, ENST00000594673, ENST00000595373, ENST00000595463, ENST00000595761, ENST00000596217, ENST00000596437, ENST00000597029, ENST00000597723, ENST00000597814, ENST00000598301, ENST00000599186, ENST00000599560, ENST00000599567, ENST00000599788, ENST00000599830, ENST00000600583, ENST00000600645, ENST00000600935, ENST00000601665, ENST00000700473, ENST00000700474, ENST00000700475, ENST00000700476, ENST00000700477, ENST00000700478, ENST00000857985, ENST00000857986, ENST00000857987, ENST00000857988, ENST00000857989, ENST00000857990, ENST00000857991, ENST00000857992, ENST00000857993, ENST00000857994, ENST00000940396, ENST00000940397, ENST00000940398, ENST00000940399, ENST00000940400, ENST00000940401, ENST00000940402, ENST00000940403, ENST00000940404, ENST00000940405, ENST00000940406, ENST00000940407, ENST00000950731, ENST00000950732, ENST00000950733, ENST00000950734, ENST00000950735, ENST00000950736, ENST00000950737, ENST00000950738, ENST00000950739, ENST00000950740, ENST00000950741, ENST00000950742, ENST00000950743, ENST00000950744, ENST00000950745, ENST00000950746, ENST00000950747, ENST00000950748, ENST00000950749, ENST00000950750, ENST00000950751, ENST00000950752

RefSeq mRNA: 5 — MANE Select: NM_016553 NM_001193357, NM_012346, NM_016553, NM_153718, NM_153719

CCDS: CCDS12788

Canonical transcript exons

ENST00000352066 — 3 exons

Exon	Start	End
ENSE00003463754	49927694	49927815
ENSE00003901861	49929326	49929504
ENSE00003904059	49906825	49909884

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 94.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2009 / max 91.3627, expressed in 1374 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182118	33.4684	1817
182117	10.2059	1529
182119	1.6975	1186
182120	0.9692	389
182121	0.2562	88
182115	0.1357	69
182114	0.1073	51
182122	0.0271	9
182116	0.0079	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.20	gold quality
left testis	UBERON:0004533	94.16	gold quality
granulocyte	CL:0000094	93.79	gold quality
endometrium epithelium	UBERON:0004811	93.55	gold quality
embryo	UBERON:0000922	93.37	gold quality
ganglionic eminence	UBERON:0004023	93.36	gold quality
monocyte	CL:0000576	92.97	gold quality
oocyte	CL:0000023	92.78	gold quality
testis	UBERON:0000473	92.55	gold quality
leukocyte	CL:0000738	92.50	gold quality
mononuclear cell	CL:0000842	92.47	gold quality
cortical plate	UBERON:0005343	92.45	gold quality
vermiform appendix	UBERON:0001154	92.05	gold quality
ventricular zone	UBERON:0003053	91.70	gold quality
gluteal muscle	UBERON:0002000	90.83	gold quality
lymph node	UBERON:0000029	90.63	gold quality
secondary oocyte	CL:0000655	90.59	gold quality
right adrenal gland	UBERON:0001233	90.41	gold quality
stromal cell of endometrium	CL:0002255	90.40	gold quality
smooth muscle tissue	UBERON:0001135	90.30	gold quality
right adrenal gland cortex	UBERON:0035827	90.24	gold quality
left adrenal gland	UBERON:0001234	90.21	gold quality
gastrocnemius	UBERON:0001388	90.00	gold quality
caecum	UBERON:0001153	89.89	gold quality
left adrenal gland cortex	UBERON:0035825	89.68	gold quality
pancreatic ductal cell	CL:0002079	89.64	silver quality
muscle of leg	UBERON:0001383	89.50	gold quality
adrenal gland	UBERON:0002369	89.10	gold quality
cerebellar hemisphere	UBERON:0002245	89.09	gold quality
adrenal cortex	UBERON:0001235	89.04	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	1501.87
E-GEOD-75367	yes	106.11
E-ANND-3	yes	10.01
E-CURD-10	no	368.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting NUP62, 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-513B-5P	99.99	69.96	2150
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-3085-5P	97.72	65.43	544
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-1227-3P	97.36	66.94	834

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 79.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 37)

• Relocation of cellular proteins and inhibition of nuclear import in HeLa cells during rhinovirus type 14 infections correlated with the degradation of p62 (PMID:12163599)
• The formation of Nup358/p62 and p62/Nup153 complexes was restricted to interphase cells, whereas Nup214/p62 binding was detected in interphase as well as during mitosis. (PMID:16730000)
• p62 has a cell type-specific role and is important in the degeneration of the basal ganglia in humans (PMID:16786527)
• autoantibodies reacting with the 60 kDa component of NPCs target p62 nucleoporin (PMID:17960595)
• Nuclear envelope permeabilization was accompanied by hyperphosphorylation of Nup62 in cells infected with wild-type mengovirus, whereas both of these alterations were suppressed in L-deficient virus mutants. (PMID:19144712)
• Oxidative stress up-regulated the binding of Crm1 to Ran and affected multiple repeat-containing nucleoporins by changing their localization, phosphorylation, O-glycosylation, or interaction with other transport components. (PMID:19828735)
• Site-directed mutagenesis of putative cleavage sites in Nup62 identified six different positions that are cleaved by 2A(pro) in vitro. This analysis revealed that 2A(pro) cleavage sites were located between amino acids 103 and 298 in Nup62 (PMID:20622012)
• impact of overexpressed ORP8 on nSREBPs and their target mRNAs was inhibited in cells depleted of Nup62 (PMID:21698267)
• the cellular Nup62 is specifically recruited by HIV-1 IN and contribute to an efficient viral DNA integration. (PMID:22308026)
• Nup62 protein intact and properly localized in HSV-1-infected cells, and an ICP27 mutant deficient for Nup62 binding failed to inhibit cellular nucleocytoplasmic transport pathways. (PMID:22334672)
• Nucleoporin p62 (NUP62) and nucleoporin 214 (NUP214) are differentially distributed between nuclear pore complexes. (PMID:22558357)
• Nup62 and Nup88 protein levels were significantly decreased upon knockdown of O-GlcNAc transferase. (PMID:23777819)
• Loss of presenilin (PS)1 function propagates tau accumulation through impairment of cargo-receptor protein p62-dependent tau degradation. (PMID:23794287)
• that a patch of hydrophobic residues, 65LRLCV69, within the zinc-binding domain of HPV16 E7 mediates its nuclear import via hydrophobic interactions with the FG domain of the central channel nucleoporin Nup62. (PMID:24074597)
• Nup62 depletion leads to the appearance of multinucleated cells and induces the formation of multipolar centrosomes, centriole synthesis defects, dramatic spindle orientation defects, and centrosome component rearrangements that impair cell bi-polarity. (PMID:24107630)
• 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)
• 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)
• Knockdown of Nup62 (and CaMKK2) reduced androgen receptor transcriptional activity in castrate resistant prostate cancer cells. (PMID:26552607)
• it was revealed that a fraction of Nup62 was associated with mitotic spindle microtubule instead of spindle matrix, and the localization of Nup62 in the mitotic spindle depended on its three coiled-coil domains rather than Crm1, although Nup62 strongly interacted with Crm1 during mitosis. Moreover, depletion of Nup62 by small interference of RNA seriously induced the defects of chromosome alignment and spindle assembly (PMID:27298184)
• ROCK-dependent phosphorylation of NUP62 regulates p63 nuclear transport and squamous cell carcinoma proliferation. (PMID:29217659)
• XIAP enhanced cancer cell proliferation, viability, and colony formation in vitro via suppression of p62. In addition, we demonstrated that XIAP-enhanced tumor growth is dependent on depletion of p62 in vivo. Herein, we have therefore delineated a novel mechanism by which XIAP contributes to development and progression of breast and colon carcinoma (PMID:30275562)
• Using a rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) to SpMNs and CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time (PMID:31157617)
• NUP62 is required for the maintenance of the spindle assembly checkpoint and chromosomal stability. (PMID:32905854)
• DEAD-Box Helicase 3 X-Linked Promotes Metastasis by Inducing Epithelial-Mesenchymal Transition via p62/Sequestosome-1. (PMID:33386519)
• Nuclear Pore Complex 62 Promotes Metastasis of Gastric Cancer by Regulating Wnt/beta-Catenin and TGF-beta Signaling Pathways. (PMID:33822519)
• The low expression of NUP62CL indicates good prognosis and high level of immune infiltration in lung adenocarcinoma. (PMID:33934535)
• p62-containing, proteolytically active nuclear condensates, increase the efficiency of the ubiquitin-proteasome system. (PMID:34385323)
• Alterations of the 70 kDa heat shock protein (HSP70) and sequestosome-1 (p62) in women with breast cancer. (PMID:34782665)
• NSP9 of SARS-CoV-2 attenuates nuclear transport by hampering nucleoporin 62 dynamics and functions in host cells. (PMID:34844119)
• Mislocalization of Nup62 Contributes to TDP-43 Proteinopathy in ALS/FTLD. (PMID:36001801)
• Acetylation of Nup62 by TIP60 ensures accurate chromosome segregation in mitosis. (PMID:36190325)
• The TRAF2-p62 axis promotes proliferation and survival of liver cancer by activating mTORC1 pathway. (PMID:37081115)
• Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. (PMID:37174682)
• Realgar-Induced Neurotoxicity: Crosstalk Between the Autophagic Flux and the p62-NRF2 Feedback Loop Mediates p62 Accumulation to Promote Apoptosis. (PMID:37400749)
• S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy. (PMID:37802024)
• Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients. (PMID:38322164)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup62l	ENSDARG00000020527
mus_musculus	Nup62	ENSMUSG00000109511
rattus_norvegicus	Nup62	ENSRNOG00000048733

Paralogs (1): NUP62CL (ENSG00000198088)

Protein

Protein identifiers

Nuclear pore glycoprotein p62 — P37198 (reviewed: P37198)

Alternative names: 62 kDa nucleoporin, Nucleoporin Nup62

All UniProt accessions (9): P37198, M0QX10, M0QX13, M0QX64, M0QXN5, M0QYY0, M0QZL5, M0R1S1, M0R302

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the nuclear pore complex. The N-terminal is probably involved in nucleocytoplasmic transport. The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex. Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation. It might be involved in protein recruitment to the centrosome after nuclear breakdown.

Subunit / interactions. Component of the p62 complex, a complex at least composed of NUP62, NUP54, and NUP58. Interacts with NUP88. Interacts with NUTF2. Interacts with HIKESHI. Interacts with OSBPL8. Interacts with CAPG. Interacts with SAS6 and TUBG1 at the centrosome. Interacts with MCM3AP isoform GANP. (Microbial infection) Interacts with Epstein-barr virus BGLF4; this interaction allows BGLF4 nuclear entry.

Subcellular location. Nucleus. Nuclear pore complex. Cytoplasm. Cytoskeleton. Spindle pole. Nucleus envelope. Microtubule organizing center. Centrosome.

Post-translational modifications. O-glycosylated. Contains about 10 N-acetylglucosamine side chain sites predicted for the entire protein, among which only one in the C-terminal. The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.

Disease relevance. Infantile striatonigral degeneration (SNDI) [MIM:271930] Neurological disorder characterized by symmetrical degeneration of the caudate nucleus, putamen, and occasionally the globus pallidus, with little involvement of the rest of the brain. The clinical features include developmental regression, choreoathetosis, dystonia, spasticity, dysphagia, failure to thrive, nystagmus, optic atrophy, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Contains FG repeats.

Similarity. Belongs to the nucleoporin NSP1/NUP62 family.

RefSeq proteins (5): NP_001180286, NP_036478, NP_057637, NP_714940, NP_714941 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007758	Nucleoporin_NSP1_C	Domain
IPR026010	NSP1/NUP62	Family

Pfam: PF05064

UniProt features (29 total): repeat 5, region of interest 4, sequence variant 4, compositionally biased region 3, modified residue 3, sequence conflict 3, glycosylation site 2, disulfide bond 2, initiator methionine 1, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7R5K	ELECTRON MICROSCOPY	12
5IJN	ELECTRON MICROSCOPY	21.4
5IJO	ELECTRON MICROSCOPY	21.4
7PER	ELECTRON MICROSCOPY	35
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P37198-F1	60.73	0.26

Functional residue map

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

Post-translational modifications (3): 2, 408, 418

Disulfide bonds (2): 475, 506

Glycosylation sites (2): 373, 468

Function

Pathways and Gene Ontology

Reactome pathways

32 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-9615933	Postmitotic nuclear pore complex (NPC) reformation

MSigDB gene sets: 501 (showing top): MORF_MTA1, GOBP_MITOTIC_CYTOKINESIS, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, E2F4DP1_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, CMYB_01

GO Biological Process (26): RNA export from nucleus (GO:0006405), protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), mitotic metaphase chromosome alignment (GO:0007080), centrosome cycle (GO:0007098), mitotic centrosome separation (GO:0007100), cell surface receptor signaling pathway (GO:0007166), negative regulation of cell population proliferation (GO:0008285), regulation of signal transduction (GO:0009966), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), negative regulation of apoptotic process (GO:0043066), negative regulation of programmed cell death (GO:0043069), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of DNA-templated transcription (GO:0045893), regulation of Ras protein signal transduction (GO:0046578), negative regulation of Ras protein signal transduction (GO:0046580), positive regulation of centriole replication (GO:0046601), mRNA transport (GO:0051028), regulation of mitotic spindle organization (GO:0060236), cellular senescence (GO:0090398), centriole assembly (GO:0098534), positive regulation of mitotic cytokinetic process (GO:1903438), positive regulation of protein localization to centrosome (GO:1904781), protein transport (GO:0015031)

GO Molecular Function (10): chromatin binding (GO:0003682), phospholipid binding (GO:0005543), structural constituent of nuclear pore (GO:0017056), signaling receptor complex adaptor activity (GO:0030159), Hsp70 protein binding (GO:0030544), SH2 domain binding (GO:0042169), ubiquitin binding (GO:0043130), PTB domain binding (GO:0051425), Hsp90 protein binding (GO:0051879), protein binding (GO:0005515)

GO Cellular Component (13): spindle pole (GO:0000922), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), nuclear membrane (GO:0031965), nuclear pore central transport channel (GO:0044613), mitotic spindle (GO:0072686), Flemming body (GO:0090543), ribonucleoprotein complex (GO:1990904), nucleus (GO:0005634), cytoskeleton (GO:0005856)

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
RNA transport	2
mitotic cell cycle process	2
mitotic nuclear division	2
signal transduction	2
negative regulation of cellular process	2
epidermal growth factor receptor signaling pathway	2
regulation of epidermal growth factor receptor signaling pathway	2
positive regulation of cell cycle process	2
Ras protein signal transduction	2
binding	2
nuclear pore	2
heat shock protein binding	2
protein domain specific binding	2
spindle	2
nucleus	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
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
cell cycle process	1
microtubule organizing center organization	1
centrosome separation	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
negative regulation of ERBB signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
programmed cell death	1

Protein interactions and networks

STRING

1646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP62	NUP54	Q7Z3B4	999
NUP62	NUP93	Q8N1F7	992
NUP62	NUP214	P35658	991
NUP62	NUP153	P49790	989
NUP62	NUP58	Q9BVL2	987
NUP62	NUTF2	P13662	982
NUP62	NUP88	Q99567	977
NUP62	NUP98	P52948	969
NUP62	RGPD1	P0C839	944
NUP62	RANBP2	P49792	939
NUP62	NUP35	Q8NFH5	932
NUP62	NUP107	P57740	901
NUP62	NUP50	Q9UKX7	895
NUP62	NPIPA1	Q9UND3	886
NUP62	NDC1	Q9BTX1	879

IntAct

471 interactions, top by confidence:

A	B	Type	Score
NUP62	NUP54	psi-mi:“MI:0915”(physical association)	0.940
NUP54	NUP62	psi-mi:“MI:0915”(physical association)	0.940
NUP62	NUP58	psi-mi:“MI:0915”(physical association)	0.890
THAP1	NUP62	psi-mi:“MI:0915”(physical association)	0.890
NUP58	NUP62	psi-mi:“MI:0915”(physical association)	0.890
NUP62	NXF1	psi-mi:“MI:0915”(physical association)	0.880
NXF1	NUP62	psi-mi:“MI:0915”(physical association)	0.880
NUP62	PHF21A	psi-mi:“MI:0915”(physical association)	0.870
NUP62	WASHC3	psi-mi:“MI:0915”(physical association)	0.870
PHF21A	NUP62	psi-mi:“MI:0915”(physical association)	0.870
WASHC3	NUP62	psi-mi:“MI:0915”(physical association)	0.870
DDX19A	MIF4GD	psi-mi:“MI:0914”(association)	0.860
FABP3	NUP62	psi-mi:“MI:0915”(physical association)	0.780
NUP62	NUTF2	psi-mi:“MI:0915”(physical association)	0.780
NUTF2	NUP62	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (443): NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid), NUP62 (Two-hybrid)

ESM2 similar proteins: A6S9N4, A7Z035, B2AWS3, F4ID16, G0S381, G0S4X2, G0SAK3, G0SBQ3, G0SBS8, G0SDP9, G5EEH9, P0CT30, P14907, P17955, P32499, P37198, P48837, P49686, P49793, P52594, P52948, P54727, P70581, Q02199, Q02629, Q02630, Q09793, Q10168, Q14677, Q2H922, Q2TA45, Q54EQ8, Q63850, Q6C908, Q6CHN0, Q6P0U9, Q6PFD9, Q7JXF5, Q7K0D8, Q7SAT8

Diamond homologs: G0SBQ3, P14907, P17955, P37198, Q10168, Q63850, Q7JXF5, Q9H1M0, Q8L7F7

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
NUTF2	“up-regulates activity”	NUP62	binding
NUP62	“up-regulates activity”	SASS6	binding
NUP62	“up-regulates activity”	TUBG1	binding
MAPK12	“down-regulates quantity by destabilization”	NUP62	phosphorylation
NUP62	“form complex”	p62_complex	binding
NUP62	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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
NEP/NS2 Interacts with the Cellular Export Machinery	8	52.2×	3e-10
Nuclear import of Rev protein	8	50.7×	3e-10
IPs transport between nucleus and cytosol	7	50.3×	2e-09
IP3 and IP4 transport between cytosol and nucleus	7	50.3×	2e-09
IP6 and IP7 transport between cytosol and nucleus	7	50.3×	2e-09
Transport of the SLBP independent Mature mRNA	8	49.2×	3e-10
Transport of the SLBP Dependant Mature mRNA	8	47.9×	3e-10
Rev-mediated nuclear export of HIV RNA	8	47.9×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein export from nucleus	5	38.1×	3e-05
nucleocytoplasmic transport	6	35.1×	9e-06
mRNA transport	6	23.6×	3e-05
protein import into nucleus	7	15.1×	5e-05
chromosome segregation	5	13.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1164 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49929401:G:GG	donor_gain	1.0000
19:49929001:G:T	donor_gain	0.9900
19:49929397:TGGA:T	donor_gain	0.9900
19:49929398:GGA:G	donor_gain	0.9900
19:49929398:GGAG:G	donor_gain	0.9900
19:49929399:GA:G	donor_gain	0.9900
19:49929399:GAG:G	donor_gain	0.9900
19:49921414:T:TA	donor_gain	0.9800
19:49929396:ATGGA:A	donor_gain	0.9800
19:49929400:AGT:A	donor_loss	0.9800
19:49929405:G:GG	donor_gain	0.9800
19:49929857:G:GA	donor_gain	0.9800
19:49908204:C:CA	donor_gain	0.9700
19:49908306:T:TA	donor_gain	0.9700
19:49909882:TTT:T	acceptor_gain	0.9700
19:49909885:C:CC	acceptor_gain	0.9700
19:49928888:G:GT	donor_gain	0.9700
19:49929403:GAGTA:G	donor_loss	0.9700
19:49929404:A:AG	donor_gain	0.9700
19:49929404:AGT:A	donor_loss	0.9700
19:49929416:CCT:C	donor_gain	0.9700
19:49929782:TGTA:T	donor_gain	0.9700
19:49929856:T:TA	donor_gain	0.9700
19:49927693:CCG:C	donor_gain	0.9600
19:49928667:A:AC	donor_gain	0.9600
19:49928668:A:C	donor_gain	0.9600
19:49929001:G:GT	donor_gain	0.9600
19:49929411:GCTTA:G	donor_loss	0.9600
19:49929412:CTTAC:C	donor_loss	0.9600
19:49929413:TTACC:T	donor_loss	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000113894 (19:49920160 G>A), RS1000119806 (19:49925428 C>A,G,T), RS1000193604 (19:49915036 G>A), RS1000335013 (19:49914457 A>C,G), RS1000359557 (19:49930602 C>G,T), RS1000464848 (19:49920506 C>G,T), RS1000808252 (19:49918079 T>C), RS1000892118 (19:49924276 A>G), RS1000913718 (19:49929422 C>T), RS1000938946 (19:49913503 G>A), RS1000941539 (19:49923100 C>T), RS1001037909 (19:49909099 G>A), RS1001068468 (19:49919048 G>A), RS1001272530 (19:49929717 C>T), RS1001276369 (19:49912164 A>C,G)

Disease associations

OMIM: gene MIM:605815 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
familial infantile bilateral striatal necrosis	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Disputed	AR

Mondo (2): infantile bilateral striatal necrosis (MONDO:0015518), familial infantile bilateral striatal necrosis (MONDO:0010080)

Orphanet (1): Infantile bilateral striatal necrosis (Orphanet:1576)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001276	Hypertonia
HP:0001285	Spastic tetraparesis
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002063	Rigidity
HP:0002066	Gait ataxia
HP:0002167	Abnormal speech pattern
HP:0002273	Tetraparesis
HP:0002359	Frequent falls
HP:0002376	Developmental regression
HP:0002396	Cogwheel rigidity
HP:0002446	Astrocytosis
HP:0002505	Loss of ambulation
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign
HP:0003593	Infantile onset

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9523	IL4I1, NUP62		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, decreases expression	3
sodium arsenite	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Asbestos, Crocidolite	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
dicrotophos	increases expression	1
urushiol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
salinomycin	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
benzo(e)pyrene	decreases methylation	1
di-n-butylphosphoric acid	affects expression	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
LDN 193189	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Benzophenoneidum	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1

Clinical trials (associated diseases)

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