NUP93

Summary

NUP93 (nucleoporin 93, HGNC:28958) is a protein-coding gene on chromosome 16q13, encoding Nuclear pore complex protein Nup93 (Q8N1F7). Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. It is a common-essential gene (DepMap: required in 100.0% of cancer 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. This gene encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9688 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 12 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 341 total — 6 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_014669

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28958
Approved symbol	NUP93
Name	nucleoporin 93
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0095
Ensembl gene	ENSG00000102900
Ensembl biotype	protein_coding
OMIM	614351
Entrez	9688

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 41 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000308159, ENST00000542526, ENST00000562496, ENST00000563405, ENST00000563437, ENST00000563465, ENST00000563486, ENST00000563858, ENST00000564278, ENST00000564887, ENST00000566315, ENST00000566678, ENST00000566727, ENST00000567081, ENST00000567641, ENST00000568283, ENST00000568656, ENST00000569322, ENST00000569595, ENST00000569842, ENST00000569863, ENST00000873103, ENST00000873104, ENST00000873105, ENST00000873106, ENST00000873107, ENST00000873108, ENST00000873109, ENST00000873110, ENST00000873111, ENST00000873112, ENST00000873113, ENST00000923931, ENST00000923932, ENST00000923933, ENST00000923934, ENST00000923935, ENST00000923936, ENST00000923937, ENST00000923938, ENST00000923939, ENST00000923940, ENST00000961440, ENST00000961441, ENST00000961442, ENST00000961443

RefSeq mRNA: 3 — MANE Select: NM_014669 NM_001242795, NM_001242796, NM_014669

CCDS: CCDS10769, CCDS55996

Canonical transcript exons

ENST00000308159 — 22 exons

Exon	Start	End
ENSE00000684678	56821504	56821593
ENSE00000684680	56823707	56823846
ENSE00000684681	56828977	56829109
ENSE00000684685	56833215	56833406
ENSE00000684686	56834128	56834254
ENSE00000684688	56834370	56834442
ENSE00000684689	56834734	56834778
ENSE00000684690	56836601	56836717
ENSE00000684692	56837608	56837726
ENSE00000684693	56838952	56839069
ENSE00000684695	56839521	56839604
ENSE00000945424	56830528	56830685
ENSE00001166384	56831842	56832007
ENSE00001166446	56748234	56748426
ENSE00002264038	56844499	56850286
ENSE00002582594	56730129	56730211
ENSE00003483965	56832295	56832388
ENSE00003491725	56841705	56841833
ENSE00003579067	56818664	56818738
ENSE00003649951	56805504	56805632
ENSE00003657147	56798476	56798538
ENSE00003691423	56758538	56758655

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8427 / max 218.4120, expressed in 1814 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154274	21.3695	1813
154279	1.5824	242
154280	0.5052	148
154284	0.2691	99
154281	0.0569	32
154275	0.0222	9
154277	0.0142	2
154278	0.0133	6
154276	0.0099	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.78	gold quality
ganglionic eminence	UBERON:0004023	97.58	gold quality
left lobe of thyroid gland	UBERON:0001120	96.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.75	gold quality
right lobe of thyroid gland	UBERON:0001119	96.61	gold quality
right testis	UBERON:0004534	96.39	gold quality
left testis	UBERON:0004533	96.34	gold quality
thyroid gland	UBERON:0002046	95.90	gold quality
embryo	UBERON:0000922	95.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.68	gold quality
testis	UBERON:0000473	95.53	gold quality
cortical plate	UBERON:0005343	95.34	gold quality
oocyte	CL:0000023	94.99	gold quality
granulocyte	CL:0000094	94.84	gold quality
lower esophagus mucosa	UBERON:0035834	94.09	gold quality
mucosa of transverse colon	UBERON:0004991	94.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.01	gold quality
secondary oocyte	CL:0000655	93.99	gold quality
metanephros cortex	UBERON:0010533	93.92	gold quality
stromal cell of endometrium	CL:0002255	93.81	gold quality
nerve	UBERON:0001021	93.56	gold quality
tibial nerve	UBERON:0001323	93.56	gold quality
skin of abdomen	UBERON:0001416	93.32	gold quality
skin of leg	UBERON:0001511	93.25	gold quality
spleen	UBERON:0002106	92.92	gold quality
leukocyte	CL:0000738	92.89	gold quality
monocyte	CL:0000576	92.86	gold quality
ectocervix	UBERON:0012249	92.84	gold quality
mononuclear cell	CL:0000842	92.81	gold quality
endothelial cell	CL:0000115	92.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting NUP93, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-1229-5P	94.57	65.78	487

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• Caspases target only Nup93 and Nup96 within the core structure of the nuclear pore complex (PMID:16286466)
• NUP93 and exportin 5 interact with the signaling protein SMAD4 and that NUP93 mutations abrogated interaction with SMAD4 (PMID:26878725)
• we show that knockdown of Nup188 or its binding partner Nup93 leads to a loss of cilia during embryonic development while leaving NPC function largely intact. Many data, including the localization of endogenous Nup188/93 at cilia bases, support their direct role at cilia. Super-resolution imaging of Nup188 shows two barrel-like structures (PMID:27593162)
• Apart from a high etiological fraction of NPHS2 and WT1 genes, study has identified an unexpectedly high frequency of a limited set of presumably ancestral NUP93 causative mutations a longitudinal collection of Central European (Czech and Slovak) patients with steroid-resistant nephrotic syndrome. (PMID:29869118)
• Two rare compound heterozygous variants of NUP93 were identified by whole exome sequencing in two brothers with isolated cerebellar atrophy (PMID:30741391)
• The expression of nsp1 in HEK cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation, while the nuclear lamina remains unperturbed. (PMID:30943371)
• This study verified that Nup93 is an important gene in cervical cancer, which could promote an aggressive behavior. (PMID:31774908)
• Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling. (PMID:31959624)
• Molecular and structural analysis of central transport channel in complex with Nup93 of nuclear pore complex. (PMID:33085133)
• Nup93 and CTCF modulate spatiotemporal dynamics and function of the HOXA gene locus during differentiation. (PMID:34746948)
• Nucleoporin 93 mediates beta-catenin nuclear import to promote hepatocellular carcinoma progression and metastasis. (PMID:34767927)
• Nucleoporin-93 reveals a common feature of aggressive breast cancers: robust nucleocytoplasmic transport of transcription factors. (PMID:35196484)
• Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model. (PMID:35211795)
• Nucleoporin 93, a new substrate of the E3 ubiquitin protein ligase HECTD1, promotes esophageal squamous cell carcinoma progression. (PMID:37993750)
• Nucleoporin93 limits Yap activity to prevent endothelial cell senescence. (PMID:38348753)
• Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children. (PMID:38650033)
• Transcription Factor yin-Yang 1 augments nucleoporin 93 oncogene activity and modulates bladder Cancer malignancy. (PMID:38857852)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup93	ENSDARG00000003487
mus_musculus	Nup93	ENSMUSG00000032939
rattus_norvegicus	Nup93	ENSRNOG00000018564
drosophila_melanogaster	Nup93-1	FBGN0027537
drosophila_melanogaster	Nup93-2	FBGN0038274
caenorhabditis_elegans	npp-13	WBGENE00003799

Protein

Protein identifiers

Nuclear pore complex protein Nup93 — Q8N1F7 (reviewed: Q8N1F7)

Alternative names: 93 kDa nucleoporin, Nucleoporin Nup93

All UniProt accessions (14): Q8N1F7, H3BM93, H3BMX0, H3BNG7, H3BNN5, H3BP72, H3BP95, H3BPA9, H3BRD9, H3BRI8, H3BV11, H3BV15, H3BVE2, H3BVG0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling.

Subunit / interactions. Part of the nuclear pore complex (NPC). Component of the p62 complex, a complex composed of NUP62 and NUP54. Forms a complex with NUP35, NUP155, NUP205 and lamin B; the interaction with NUP35 is direct. Does not interact with TPR. Interacts with SMAD4 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling. (Microbial infection) Interacts with SARS-CoV translation inhibitor nsp1; this interaction may disrupt nuclear pore function.

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

Disease relevance. Nephrotic syndrome 12 (NPHS12) [MIM:616892] A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. NPHS12 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nucleoporin interacting component (NIC) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N1F7-1	1	yes
Q8N1F7-2	2

RefSeq proteins (3): NP_001229724, NP_001229725, NP_055484* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007231	Nucleoporin_int_Nup93/Nic96	Family

Pfam: PF04097

UniProt features (64 total): helix 40, modified residue 8, turn 6, sequence variant 4, strand 4, chain 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7MW0	X-RAY DIFFRACTION	2
7MW1	X-RAY DIFFRACTION	3.4
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-Q8N1F7-F1	80.40	0.22

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 (8): 49, 52, 66, 72, 75, 80, 430, 767

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: 350 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NUCLEAR_PORE_ORGANIZATION, GOBP_NUCLEAR_TRANSPORT, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP, REACTOME_HIV_INFECTION, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_NUCLEUS_ORGANIZATION, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PORE_COMPLEX_ASSEMBLY

GO Biological Process (8): protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), nuclear envelope organization (GO:0006998), poly(A)+ mRNA export from nucleus (GO:0016973), nuclear pore complex assembly (GO:0051292), positive regulation of SMAD protein signal transduction (GO:0060391), protein transport (GO:0015031), mRNA transport (GO:0051028)

GO Molecular Function (2): structural constituent of nuclear pore (GO:0017056), protein binding (GO:0005515)

GO Cellular Component (8): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), nuclear periphery (GO:0034399), 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	3
nucleus	2
nuclear envelope	2
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
nuclear transport	1
nucleus organization	1
endomembrane system organization	1
membrane organization	1
mRNA export from nucleus	1
nuclear pore organization	1
pore complex assembly	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
RNA transport	1
structural molecule activity	1
nuclear pore	1
nucleocytoplasmic transport	1
binding	1
endomembrane system	1
organelle envelope	1
nuclear protein-containing complex	1
centriole	1
microtubule organizing center	1
cytoplasm	1
organelle membrane	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP93	NUP35	Q8NFH5	999
NUP93	NUP205	Q92621	998
NUP93	NUP62	P37198	992
NUP93	NUP155	O75694	991
NUP93	NUP188	Q5SRE5	986
NUP93	SH2D3A	Q9BRG2	958
NUP93	NUP107	P57740	943
NUP93	NDC1	Q9BTX1	932
NUP93	NUP54	Q7Z3B4	922
NUP93	NUP58	Q9BVL2	912
NUP93	NUP153	P49790	899
NUP93	NUP98	P52948	898
NUP93	NUP88	Q99567	884
NUP93	NUP160	Q12769	883
NUP93	NUP133	Q8WUM0	880

IntAct

177 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PLA2G6	NUP93	psi-mi:“MI:0915”(physical association)	0.560
MPPED2	NUP93	psi-mi:“MI:0915”(physical association)	0.560
OPCML	NUP93	psi-mi:“MI:0915”(physical association)	0.560
AP5Z1	NUP93	psi-mi:“MI:0915”(physical association)	0.560
NUP93	TMEM100	psi-mi:“MI:0915”(physical association)	0.560
NUP93		psi-mi:“MI:0915”(physical association)	0.550
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
AIRE	NUP93	psi-mi:“MI:0915”(physical association)	0.400
Nup214	OGT	psi-mi:“MI:0915”(physical association)	0.400
Nup188		psi-mi:“MI:0915”(physical association)	0.400
AHCTF1	NUP155	psi-mi:“MI:0915”(physical association)	0.400
NUP35	NUP93	psi-mi:“MI:0915”(physical association)	0.370
NUP93	E7	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Nup98	POM121C	psi-mi:“MI:0914”(association)	0.350
Nup107	POM121C	psi-mi:“MI:0914”(association)	0.350
Nup188	RPS3	psi-mi:“MI:0914”(association)	0.350
Ranbp2	POM121C	psi-mi:“MI:0914”(association)	0.350
Kifc5b	KPNA3	psi-mi:“MI:0914”(association)	0.350
Nup214	NUP155	psi-mi:“MI:0914”(association)	0.350
Rcc1	WDR46	psi-mi:“MI:0914”(association)	0.350
Ube2i	POM121C	psi-mi:“MI:0914”(association)	0.350
NUP153	POM121C	psi-mi:“MI:0914”(association)	0.350

BioGRID (358): NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), NUP93 (Affinity Capture-MS), FGG (Co-fractionation), MTPN (Co-fractionation), NUP205 (Co-fractionation), NUP93 (Co-fractionation), NUP93 (Co-fractionation), NUP93 (Co-fractionation), UCHL3 (Co-fractionation)

ESM2 similar proteins: A1A4I9, A5D796, A5PJZ5, A7S2N8, A9ULY7, B0F9L4, B2GV24, F4HQ84, F4IDS7, O60308, O75694, O75717, O94874, P32780, P37199, P59328, Q14CX7, Q1RMS6, Q28HX4, Q4R367, Q5R822, Q5RBW9, Q5ZL91, Q5ZMG1, Q66HC5, Q6DDM4, Q6NX12, Q6P3X3, Q6PGY6, Q7TQK1, Q7ZU29, Q7ZX96, Q8BGQ1, Q8BJ71, Q8BWZ3, Q8CCJ3, Q8JGR7, Q8N1F7, Q8R3N6, Q8WVM7

Diamond homologs: A5PJZ5, Q5R822, Q66HC5, Q6NX12, Q7ZU29, Q7ZX96, Q8BJ71, Q8N1F7, Q9XZ06, O14310

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUP93	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 202 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
Postmitotic nuclear pore complex (NPC) reformation	9	26.8×	4e-09
Rev-mediated nuclear export of HIV RNA	11	25.5×	2e-10
NEP/NS2 Interacts with the Cellular Export Machinery	10	25.3×	1e-09
Nuclear import of Rev protein	10	24.5×	1e-09
Transport of Ribonucleoproteins into the Host Nucleus	9	23.4×	1e-08
IPs transport between nucleus and cytosol	8	22.2×	8e-08
IP3 and IP4 transport between cytosol and nucleus	8	22.2×	8e-08
IP6 and IP7 transport between cytosol and nucleus	8	22.2×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	5	28.2×	2e-04
nucleocytoplasmic transport	10	23.6×	1e-08
protein export from nucleus	6	18.5×	2e-04
mRNA transport	10	15.9×	4e-07
peptidyl-tyrosine phosphorylation	6	15.2×	4e-04
mRNA export from nucleus	7	12.5×	3e-04
cell surface receptor protein tyrosine kinase signaling pathway	10	10.5×	1e-05
protein import into nucleus	12	10.4×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	11
Uncertain significance	135
Likely benign	115
Benign	46

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1403825	NM_014669.5(NUP93):c.1718_1719dup (p.Val574fs)	Pathogenic
2153332	NM_014669.5(NUP93):c.229C>T (p.Arg77Ter)	Pathogenic
224966	NM_014669.5(NUP93):c.1326del (p.Lys442fs)	Pathogenic
224967	NM_014669.5(NUP93):c.1537+1G>A	Pathogenic
3235149	NM_014669.5(NUP93):c.927+1G>A	Pathogenic
3768431	NM_014669.5(NUP93):c.724del (p.Ala241_Leu242insTer)	Pathogenic
1344649	NM_014669.5(NUP93):c.575A>G (p.Tyr192Cys)	Likely pathogenic
1961556	NM_014669.5(NUP93):c.179+1G>A	Likely pathogenic
2579691	NM_014669.5(NUP93):c.-14-1G>A	Likely pathogenic
2635055	NM_014669.5(NUP93):c.2190_2191del (p.Arg730fs)	Likely pathogenic
2743562	NM_014669.5(NUP93):c.1782+1G>C	Likely pathogenic
3062103	NM_014669.5(NUP93):c.1733G>C (p.Arg578Pro)	Likely pathogenic
3391048	NM_014669.5(NUP93):c.1732C>T (p.Arg578Ter)	Likely pathogenic
3780053	NM_014669.5(NUP93):c.406G>T (p.Glu136Ter)	Likely pathogenic
4081566	NM_014669.5(NUP93):c.1457_1458dup (p.Cys487fs)	Likely pathogenic
599141	NM_014669.5(NUP93):c.1709T>A (p.Val570Glu)	Likely pathogenic
812904	NM_014669.5(NUP93):c.1909A>G (p.Lys637Glu)	Likely pathogenic

SpliceAI

3694 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56730211:GGTA:G	donor_loss	1.0000
16:56730212:G:GA	donor_loss	1.0000
16:56748228:A:AG	acceptor_gain	1.0000
16:56748229:T:G	acceptor_gain	1.0000
16:56748229:TCTAG:T	acceptor_loss	1.0000
16:56748230:CTAGG:C	acceptor_loss	1.0000
16:56748232:A:AG	acceptor_gain	1.0000
16:56748232:A:C	acceptor_loss	1.0000
16:56748232:AG:A	acceptor_gain	1.0000
16:56748233:G:GA	acceptor_gain	1.0000
16:56748233:GG:G	acceptor_gain	1.0000
16:56748233:GGA:G	acceptor_gain	1.0000
16:56748233:GGAT:G	acceptor_gain	1.0000
16:56748233:GGATC:G	acceptor_gain	1.0000
16:56748423:AGGC:A	donor_gain	1.0000
16:56748424:GGCG:G	donor_gain	1.0000
16:56748425:GC:G	donor_gain	1.0000
16:56748427:G:GG	donor_gain	1.0000
16:56748430:A:AC	donor_loss	1.0000
16:56758533:CATA:C	acceptor_loss	1.0000
16:56758535:TA:T	acceptor_loss	1.0000
16:56758536:A:G	acceptor_loss	1.0000
16:56758537:G:GA	acceptor_loss	1.0000
16:56758537:GGTCA:G	acceptor_gain	1.0000
16:56798472:ATAG:A	acceptor_gain	1.0000
16:56798472:ATAGG:A	acceptor_gain	1.0000
16:56798473:T:G	acceptor_gain	1.0000
16:56798474:AG:A	acceptor_gain	1.0000
16:56798474:AGG:A	acceptor_gain	1.0000
16:56798475:GG:G	acceptor_gain	1.0000

AlphaMissense

5399 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56805552:T:A	W137R	1.000
16:56805552:T:C	W137R	1.000
16:56805554:G:C	W137C	1.000
16:56805554:G:T	W137C	1.000
16:56823722:T:A	W224R	1.000
16:56823722:T:C	W224R	1.000
16:56830555:T:A	W319R	1.000
16:56830555:T:C	W319R	1.000
16:56830557:G:C	W319C	1.000
16:56830557:G:T	W319C	1.000
16:56831999:T:A	W415R	1.000
16:56831999:T:C	W415R	1.000
16:56748284:G:C	A13P	0.999
16:56798483:T:C	L102P	0.999
16:56798503:G:C	A109P	0.999
16:56805566:A:C	K141N	0.999
16:56805566:A:T	K141N	0.999
16:56823837:T:C	L262P	0.999
16:56829003:T:A	V274D	0.999
16:56829060:T:A	V293D	0.999
16:56830573:T:C	C325R	0.999
16:56830575:C:G	C325W	0.999
16:56830579:C:A	R327S	0.999
16:56830580:G:C	R327P	0.999
16:56830586:G:T	G329V	0.999
16:56830601:C:A	A334D	0.999
16:56831917:G:C	K387N	0.999
16:56831917:G:T	K387N	0.999
16:56831940:G:A	G395D	0.999
16:56831990:G:C	D412H	0.999

dbSNP variants (sampled 300 via entrez): RS1000016571 (16:56773317 A>G), RS1000042140 (16:56763383 C>T), RS1000237140 (16:56822047 T>G), RS1000252539 (16:56766367 C>T), RS1000426359 (16:56760429 A>G), RS1000453498 (16:56791466 A>G), RS1000484220 (16:56733363 G>A), RS1000503100 (16:56747217 C>G,T), RS1000541020 (16:56738584 T>G), RS1000580837 (16:56839034 G>A), RS1000604710 (16:56838815 C>G), RS1000683784 (16:56784912 A>G), RS1000731953 (16:56833096 T>C), RS1000958122 (16:56746922 A>G,T), RS1001047812 (16:56797062 C>G,T)

Disease associations

OMIM: gene MIM:614351 | disease phenotypes: MIM:616892

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 12	Definitive	Autosomal recessive
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nephrotic syndrome, type 12	Definitive	AR

Mondo (4): nephrotic syndrome, type 12 (MONDO:0014817), nephrotic syndrome (MONDO:0005377), focal segmental glomerulosclerosis (MONDO:0100313), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (1): Hereditary steroid-resistant nephrotic syndrome (Orphanet:656)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000790	Hematuria
HP:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003676	Progressive
HP:0003774	Stage 5 chronic kidney disease
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012588	Steroid-resistant nephrotic syndrome
HP:0012622	Chronic kidney disease
HP:0031504	Foamy urine
HP:0100539	Periorbital edema

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000331_1	HDL cholesterol	4.000000e-93
GCST001601_1	Gambling	3.000000e-06
GCST003363_2	HDL cholesterol levels	1.000000e-16
GCST006031_12	Potassium levels	1.000000e-10
GCST010241_270	Apolipoprotein A1 levels	4.000000e-142
GCST010242_200	HDL cholesterol levels	2.000000e-235
GCST010242_78	HDL cholesterol levels	2.000000e-08
GCST010243_237	Apolipoprotein B levels	5.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004699	gambling behaviour
EFO:0009283	potassium measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725189 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.43	IC50	370	nM	MOLIBRESIB
5.81	Kd	1554	nM	CHEMBL5653589
5.81	ED50	1554	nM	CHEMBL5653589
5.49	Kd	3246	nM	CHEMBL3752910
5.49	ED50	3246	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178745: Inhibition of NUP93 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3700	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148907: Binding affinity to human NUP93 incubated for 45 mins by Kinobead based pull down assay	kd	1.5544	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148907: Binding affinity to human NUP93 incubated for 45 mins by Kinobead based pull down assay	kd	3.2458	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, affects methylation, decreases expression, increases expression	3
sodium arsenite	increases expression, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Benztropine	affects cotreatment, increases expression	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Cuprizone	affects cotreatment, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651949	Binding	Binding affinity to human NUP93 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_W912	LAM1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	PHASE3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	PHASE3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT00001212	PHASE2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	PHASE2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	PHASE2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	PHASE2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	PHASE2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT02394106	PHASE2	TERMINATED	Ofatumumab in Children With Drug Resistant Idiopathic Nephrotic Syndrome
NCT02394119	PHASE2	COMPLETED	Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT02966717	PHASE2	UNKNOWN	Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
NCT03004001	PHASE2	TERMINATED	Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
NCT03949855	PHASE2	RECRUITING	Belimumab With Rituximab for Primary Membranous Nephropathy
NCT05599815	PHASE2	WITHDRAWN	Part 1 - A Clinical Trial in Patients With Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome
NCT05704400	PHASE2	UNKNOWN	Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases