NUP160

Summary

NUP160 (nucleoporin 160, HGNC:18017) is a protein-coding gene on chromosome 11p11.2, encoding Nuclear pore complex protein Nup160 (Q12769). Functions as a component of the nuclear pore complex (NPC). It is a common-essential gene (DepMap: required in 94.2% of cancer cell lines).

A structural constituent of nuclear pore. Involved in mRNA export from nucleus and nephron development. Located in kinetochore and nuclear envelope. Part of nuclear pore outer ring. Implicated in nephrotic syndrome type 19.

Source: NCBI Gene 23279 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 19 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 23
• Clinical variants (ClinVar): 459 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 94.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_015231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18017
Approved symbol	NUP160
Name	nucleoporin 160
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0197, FLJ22583
Ensembl gene	ENSG00000030066
Ensembl biotype	protein_coding
OMIM	607614
Entrez	23279

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 24 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000378460, ENST00000526569, ENST00000526870, ENST00000527126, ENST00000527750, ENST00000528071, ENST00000528501, ENST00000529863, ENST00000530326, ENST00000531016, ENST00000532773, ENST00000694866, ENST00000694867, ENST00000863535, ENST00000863536, ENST00000863537, ENST00000863538, ENST00000863539, ENST00000935518, ENST00000935519, ENST00000935520, ENST00000935521, ENST00000935522, ENST00000935523, ENST00000935524, ENST00000935525, ENST00000935526, ENST00000935527, ENST00000935528, ENST00000935529, ENST00000935530

RefSeq mRNA: 2 — MANE Select: NM_015231 NM_001318399, NM_015231

CCDS: CCDS31484, CCDS81567

Canonical transcript exons

ENST00000378460 — 36 exons

Exon	Start	End
ENSE00001128880	47822087	47822164
ENSE00001128885	47835651	47835809
ENSE00001592503	47807070	47807140
ENSE00001606096	47798368	47798463
ENSE00001621459	47784922	47785063
ENSE00001640732	47839843	47840065
ENSE00001651558	47812064	47812224
ENSE00001696810	47791930	47791990
ENSE00001709062	47801811	47801930
ENSE00001739309	47780343	47780447
ENSE00001747115	47806153	47806312
ENSE00001749078	47797779	47797884
ENSE00001751701	47788501	47788611
ENSE00001758108	47788182	47788305
ENSE00001759225	47798168	47798262
ENSE00001763003	47803438	47803536
ENSE00001768421	47797978	47798074
ENSE00001774573	47808396	47808529
ENSE00001792894	47778118	47779194
ENSE00001801191	47792786	47792946
ENSE00001805074	47783073	47783198
ENSE00002180198	47848219	47848350
ENSE00002729505	47812302	47812429
ENSE00003515915	47786453	47786554
ENSE00003532325	47804549	47804618
ENSE00003576995	47837545	47837623
ENSE00003582950	47821724	47821821
ENSE00003589727	47819374	47819458
ENSE00003678735	47836887	47837001
ENSE00003680650	47847848	47847959
ENSE00003712879	47813316	47813415
ENSE00003721005	47818056	47818124
ENSE00003736135	47815946	47816029
ENSE00003740972	47840378	47840588
ENSE00003751402	47812882	47813047
ENSE00003752446	47815479	47815649

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 92.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0380 / max 151.2561, expressed in 1792 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119675	16.0992	1790
119677	0.7234	458
119676	0.2154	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	92.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.67	gold quality
secondary oocyte	CL:0000655	91.47	gold quality
ganglionic eminence	UBERON:0004023	91.21	gold quality
ventricular zone	UBERON:0003053	91.20	gold quality
embryo	UBERON:0000922	91.15	gold quality
germinal epithelium of ovary	UBERON:0001304	90.72	gold quality
left ovary	UBERON:0002119	89.89	gold quality
ovary	UBERON:0000992	89.68	gold quality
right ovary	UBERON:0002118	89.48	gold quality
endometrium	UBERON:0001295	89.35	gold quality
colonic epithelium	UBERON:0000397	89.16	gold quality
calcaneal tendon	UBERON:0003701	89.01	gold quality
right uterine tube	UBERON:0001302	88.98	gold quality
left lobe of thyroid gland	UBERON:0001120	88.23	gold quality
mucosa of stomach	UBERON:0001199	88.19	gold quality
body of uterus	UBERON:0009853	88.18	gold quality
body of pancreas	UBERON:0001150	88.17	gold quality
right lobe of thyroid gland	UBERON:0001119	88.04	gold quality
tibial nerve	UBERON:0001323	88.03	gold quality
thyroid gland	UBERON:0002046	87.95	gold quality
cortical plate	UBERON:0005343	87.89	gold quality
adrenal tissue	UBERON:0018303	87.81	gold quality
rectum	UBERON:0001052	87.69	gold quality
vermiform appendix	UBERON:0001154	87.55	gold quality
right lung	UBERON:0002167	87.49	gold quality
sperm	CL:0000019	87.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.42	gold quality
tonsil	UBERON:0002372	87.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting NUP160, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
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-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3134	100.00	66.43	777
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4495	99.82	72.08	3080

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 12)

• Nup107-160 complex is dynamic in mitosis and that it promotes spindle assembly in a manner that is distinct from its functions at interphase nuclear pores. (PMID:16807356)
• phosphorylation does not affect interactions within the Nup107-160 subcomplex, but regulates the association of the subcomplex with the NPC and other proteins (PMID:17360435)
• These data thus provide the first molecular clues underlying the function of the human Nup107-160 complex at kinetochores. (PMID:17363900)
• Data show that structure-guided sequence comparison of Nup160 and Saccharomyces cerevisiae Nup120 strongly suggests that both proteins adopt the same unique fold despite a low sequence identity of 10%. (PMID:19576787)
• A major function of the Nup107 complex in mitosis is to ensure the proper localization of the chromosome passenger complex at the centromere. (PMID:19864462)
• Data show that Nup107-160 promotes spindle assembly through Ran-GTP-regulated nucleation of microtubules by gamma-TuRC at kinetochores, and reveal a relationship between nucleoporins and the microtubule cytoskeleton. (PMID:20081840)
• The interactions of Nup160 with Pom121 and are predicted to assist in the formation of the nuclear pore and the anchoring of the Nuclear pore complexes to the pore membrane. (PMID:20974814)
• The SUMO-specific isopeptidase SENP2 associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex. (PMID:22031293)
• Nup107-160 complex and its partner Elys dynamically colocalize with Nup98 and CRM1 into endogenous GLFG bodies present in specific HeLa sublines. (PMID:25904327)
• transcriptome sequencing of patient-derived angiosarcoma cells, identified a novel fusion gene NUP160-SLC43A3 found to be expressed in 9 of 25 human angiosarcoma specimens that were examined. (PMID:26527604)
• Role and Mechanism of NUP160-regulated Autophagy in Pathogenesis of Diabetic Nephropathy. (PMID:38043110)
• Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children. (PMID:38650033)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup160	ENSDARG00000027140
mus_musculus	Nup160	ENSMUSG00000051329
rattus_norvegicus	Nup160	ENSRNOG00000028215
drosophila_melanogaster	Nup160	FBGN0262647
caenorhabditis_elegans	npp-6	WBGENE00003792

Protein

Protein identifiers

Nuclear pore complex protein Nup160 — Q12769 (reviewed: Q12769)

Alternative names: 160 kDa nucleoporin, Nucleoporin Nup160

All UniProt accessions (6): A0A8Q3WK58, A0A8V8NBT1, E9PR16, E9PSI3, Q12769, G3V198

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a component of the nuclear pore complex (NPC). Involved in poly(A)+ RNA transport.

Subunit / interactions. Part of the nuclear pore complex (NPC). Forms part of the NUP160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and NUP96. This complex plays a role in RNA export and in tethering NUP98 and NUP153 to the nucleus.

Subcellular location. Nucleus. Nuclear pore complex.

Disease relevance. Nephrotic syndrome 19 (NPHS19) [MIM:618178] 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 that progresses to end-stage renal failure. NPHS19 is an autosomal recessive, steroid-resistant form with onset in the first or second decade of life, resulting in chronic kidney disease. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12769-1	1	yes
Q12769-2	2
Q12769-3	3

RefSeq proteins (2): NP_001305328, NP_056046* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021717	Nucleoporin_Nup160	Family
IPR056535	TPR_NUP160_M	Domain
IPR056536	TPR_NUP160_C	Domain
IPR056547	NUP160_helical	Domain
IPR059141	Beta-prop_Nup120_160	Domain

Pfam: PF11715, PF23345, PF23347, PF23354

UniProt features (18 total): splice variant 6, sequence variant 5, modified residue 4, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7R5K	ELECTRON MICROSCOPY	12
5A9Q	ELECTRON MICROSCOPY	23
7PEQ	ELECTRON MICROSCOPY	35
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12769-F1	80.95	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 (4): 44, 490, 949, 1157

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
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-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
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-5663220	RHO GTPases Activate Formins

MSigDB gene sets: 309 (showing top): REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEAR_TRANSPORT, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, REACTOME_HIV_INFECTION, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GARY_CD5_TARGETS_DN, SCHLOSSER_SERUM_RESPONSE_DN

GO Biological Process (5): mRNA export from nucleus (GO:0006406), nucleocytoplasmic transport (GO:0006913), protein transport (GO:0015031), nephron development (GO:0072006), mRNA transport (GO:0051028)

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

GO Cellular Component (6): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), cytosol (GO:0005829), nuclear pore outer ring (GO:0031080), kinetochore (GO:0000776), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-15 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
Antimicrobial mechanism of IFN-stimulated genes	1
Amplification of signal from the kinetochores	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
Mitotic Anaphase	1
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear pore	2
nuclear protein-containing complex	2
RNA export from nucleus	1
gene expression	1
mRNA transport	1
nuclear transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
kidney development	1
anatomical structure development	1
RNA transport	1
structural molecule activity	1
nucleocytoplasmic transport	1
binding	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
cytoplasm	1
cellular anatomical structure	1
condensed chromosome, centromeric region	1
intracellular membraneless organelle	1
supramolecular complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP160	NUP107	P57740	999
NUP160	NUP133	Q8WUM0	999
NUP160	NUP85	Q9BW27	998
NUP160	NUP98	P52948	998
NUP160	NUP43	Q8NFH3	997
NUP160	NUP37	Q8NFH4	997
NUP160	SEH1L	Q96EE3	997
NUP160	AHCTF1	Q8WYP5	996
NUP160	SEC13	P55735	996
NUP160	NUP153	P49790	973
NUP160	NUP93	Q8N1F7	883
NUP160	NUP188	Q5SRE5	865
NUP160	NUP88	Q99567	859
NUP160	NUP214	P35658	848
NUP160	NUP210	Q8TEM1	816

IntAct

144 interactions, top by confidence:

A	B	Type	Score
NUP133	NUP98	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
NUP43	NUP98	psi-mi:“MI:0914”(association)	0.640
NUP85	NUP160	psi-mi:“MI:0915”(physical association)	0.590
USP12	PHLPP1	psi-mi:“MI:0914”(association)	0.570
ESRRG	NUP160	psi-mi:“MI:0915”(physical association)	0.560
NUP160	ESRRG	psi-mi:“MI:0915”(physical association)	0.560
Nup107	NUP98	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
VASN	AP3B1	psi-mi:“MI:0914”(association)	0.530
NUP43	KIF5B	psi-mi:“MI:0914”(association)	0.530
NUP107	NUP98	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
AHCTF1	NUP98	psi-mi:“MI:0915”(physical association)	0.490
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
Nup98	NUP98	psi-mi:“MI:0915”(physical association)	0.400
NUP85	NUP98	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (272): NUP160 (Two-hybrid), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), NUP133 (Co-fractionation), NUP85 (Co-fractionation), NUP160 (Affinity Capture-MS), NUP160 (Proximity Label-MS), NUP160 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8GXY4, A4D1P6, A8XSV3, B0JZ65, B0R160, B0WYR6, E9Q7R9, F1REV3, F6S215, O00443, O65418, P50748, Q09178, Q12769, Q17I16, Q19317, Q2TAW0, Q3MHH2, Q402B2, Q4V9P9, Q5R6T6, Q5RAY1, Q5RB52, Q5RE88, Q5ZJY3, Q5ZL79, Q5ZLL7, Q6DTM3, Q6GM71, Q6INI5, Q6P996, Q6X9E4, Q6ZQQ6, Q7TMQ7, Q86XI2, Q8BJW5, Q8BMQ2, Q8C3Y4, Q8K3E5, Q8N157

Diamond homologs: Q12769, Q9Z0W3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUP160	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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	11	39.0×	2e-13
Transport of Ribonucleoproteins into the Host Nucleus	12	37.2×	7e-14
IPs transport between nucleus and cytosol	11	36.4×	2e-13
IP3 and IP4 transport between cytosol and nucleus	11	36.4×	2e-13
IP6 and IP7 transport between cytosol and nucleus	11	36.4×	2e-13
Nuclear import of Rev protein	12	35.0×	8e-14
Regulation of Glucokinase by Glucokinase Regulatory Protein	11	34.1×	4e-13
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	11	34.1×	4e-13

GO biological processes:

GO term	Partners	Fold	FDR
nucleocytoplasmic transport	12	31.4×	2e-12
RNA export from nucleus	5	31.2×	1e-04
NLS-bearing protein import into nucleus	5	26.8×	2e-04
mRNA transport	9	15.8×	2e-06
protein import into nucleus	15	14.4×	8e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	261
Likely benign	118
Benign	23

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1077025	NM_015231.3(NUP160):c.4148_4149del (p.Glu1383fs)	Pathogenic
1252069	NM_015231.3(NUP160):c.1077+5G>A	Pathogenic
1941780	NM_015231.3(NUP160):c.991C>T (p.Arg331Ter)	Pathogenic
3670570	NM_015231.3(NUP160):c.3943G>T (p.Glu1315Ter)	Pathogenic
4804590	NM_015231.3(NUP160):c.1645del (p.Glu549fs)	Pathogenic
3350543	NM_015231.3(NUP160):c.2176C>T (p.Gln726Ter)	Likely pathogenic
4293754	NM_015231.3(NUP160):c.3032C>A (p.Ser1011Ter)	Likely pathogenic
4727479	NM_015231.3(NUP160):c.2271_2273+1del	Likely pathogenic

SpliceAI

5161 predictions. Top by Δscore:

Variant	Effect	Δscore
11:47779190:GACAG:G	acceptor_gain	1.0000
11:47779192:CAG:C	acceptor_gain	1.0000
11:47779193:AG:A	acceptor_gain	1.0000
11:47779195:C:CC	acceptor_gain	1.0000
11:47779197:A:C	acceptor_gain	1.0000
11:47780341:A:AC	donor_gain	1.0000
11:47780342:C:CC	donor_gain	1.0000
11:47780342:CTG:C	donor_gain	1.0000
11:47780448:C:CC	acceptor_gain	1.0000
11:47783068:CCTA:C	donor_loss	1.0000
11:47783069:CTACC:C	donor_loss	1.0000
11:47783070:TAC:T	donor_loss	1.0000
11:47783071:ACCTC:A	donor_loss	1.0000
11:47783072:C:G	donor_loss	1.0000
11:47785062:CA:C	acceptor_gain	1.0000
11:47785062:CACT:C	acceptor_gain	1.0000
11:47785064:C:CC	acceptor_gain	1.0000
11:47785065:T:C	acceptor_gain	1.0000
11:47785065:T:TC	acceptor_gain	1.0000
11:47786455:AGACT:A	donor_gain	1.0000
11:47786645:T:TA	donor_gain	1.0000
11:47788180:A:AC	donor_gain	1.0000
11:47788181:C:CC	donor_gain	1.0000
11:47788608:TTTG:T	acceptor_gain	1.0000
11:47788612:C:CC	acceptor_gain	1.0000
11:47788614:A:C	acceptor_gain	1.0000
11:47791928:A:AC	donor_gain	1.0000
11:47791929:C:CC	donor_gain	1.0000
11:47792737:A:AC	donor_gain	1.0000
11:47792738:C:CC	donor_gain	1.0000

AlphaMissense

9369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:47836898:A:G	W311R	0.999
11:47836898:A:T	W311R	0.999
11:47836903:C:G	R309P	0.999
11:47780389:A:G	L1392P	0.998
11:47783141:C:G	A1350P	0.998
11:47785047:A:G	W1289R	0.998
11:47785047:A:T	W1289R	0.998
11:47797859:G:T	A1070D	0.998
11:47836906:A:G	L308P	0.998
11:47783111:C:G	A1360P	0.997
11:47792815:A:G	W1141R	0.997
11:47792815:A:T	W1141R	0.997
11:47792943:C:T	G1098D	0.997
11:47792944:C:G	G1098R	0.997
11:47792946:G:T	A1097D	0.997
11:47797817:A:G	L1084P	0.997
11:47798039:A:G	L1041P	0.997
11:47819442:A:G	W432R	0.997
11:47819442:A:T	W432R	0.997
11:47784922:C:A	K1330N	0.996
11:47784922:C:G	K1330N	0.996
11:47797860:C:G	A1070P	0.996
11:47798012:A:G	L1050P	0.996
11:47798030:C:G	R1044P	0.996
11:47803472:C:T	G914E	0.996
11:47803481:A:G	F911S	0.996
11:47812104:A:G	L734P	0.996
11:47783110:G:T	A1360D	0.995
11:47783140:G:T	A1350D	0.995
11:47784942:A:G	W1324R	0.995

dbSNP variants (sampled 300 via entrez): RS1000014227 (11:47802207 T>A,G), RS1000039310 (11:47785761 C>T), RS1000081862 (11:47831134 G>A), RS1000092430 (11:47817063 C>A), RS1000161052 (11:47834770 G>A), RS1000168347 (11:47844374 A>G), RS1000217755 (11:47834984 G>T), RS1000262944 (11:47800585 T>G), RS1000296779 (11:47797369 G>A), RS1000346014 (11:47840997 A>G,T), RS1000360904 (11:47850412 G>T), RS1000397739 (11:47847112 T>C), RS1000426886 (11:47838503 T>A,C), RS1000460421 (11:47843998 G>A), RS1000526643 (11:47817472 G>A)

Disease associations

OMIM: gene MIM:607614 | disease phenotypes: MIM:618178, MIM:609423

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 19	Strong	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 19	Moderate	AR

Mondo (4): nephrotic syndrome, type 19 (MONDO:0032582), osteopetrosis (MONDO:0017198), susceptibility to HIV infection (MONDO:0004951), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (1): Osteopetrosis and related disorders (Orphanet:2781)

HPO phenotypes

22 total (23 of 22 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:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003621	Juvenile onset
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:0012625	Stage 3 chronic kidney disease
HP:0031504	Foamy urine
HP:0100539	Periorbital edema
HP:0011002	Osteopetrosis

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST002580_1	Intraocular pressure	1.000000e-11
GCST004607_126	Plateletcrit	2.000000e-12
GCST004608_169	Granulocyte percentage of myeloid white cells	1.000000e-09
GCST005170_48	Intraocular pressure	2.000000e-07
GCST005232_56	Neuroticism	1.000000e-16
GCST005580_145	Intraocular pressure	2.000000e-30
GCST005905_14	Global electrical heterogeneity phenotypes	6.000000e-09
GCST006923_11	Loneliness	1.000000e-07
GCST006924_13	Loneliness (MTAG)	1.000000e-08
GCST007267_69	Systolic blood pressure	2.000000e-17
GCST007269_199	Pulse pressure	3.000000e-11
GCST007559_27	Sleep duration (short sleep)	4.000000e-08
GCST007825_4	Alzheimer’s disease or fasting glucose levels (pleiotropy)	3.000000e-16
GCST008129_74	Body mass index	1.000000e-31
GCST008876_14	Non-lobar intracerebral hemorrhage (MTAG)	3.000000e-07
GCST010002_238	Refractive error	2.000000e-14
GCST010136_2	Fruit consumption	5.000000e-09
GCST010703_36	Brain morphology (MOSTest)	8.000000e-09
GCST90002399_62	Neutrophil percentage of white cells	2.000000e-09
GCST90011898_82	Alanine aminotransferase levels	9.000000e-09
GCST90011899_85	Aspartate aminotransferase levels	2.000000e-15
GCST90011900_66	Serum alkaline phosphatase levels	1.000000e-11
GCST90013406_52	Liver enzyme levels (alkaline phosphatase)	7.000000e-13

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0007985	platelet crit
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007660	neuroticism measurement
EFO:0004327	electrocardiography
EFO:0007865	loneliness measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004340	body mass index
EFO:0010178	non-lobar intracerebral hemorrhage
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010022	Osteopetrosis	C05.116.099.708.702.678

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066257 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.06	Kd	878.1	nM	CHEMBL3752910
6.06	ED50	878.1	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148902: Binding affinity to human NUP160 incubated for 45 mins by Kinobead based pull down assay	kd	0.8781	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	7
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
sodium arsenite	decreases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance	2
Nickel	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	decreases reaction, affects binding	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Arsenic	increases response to substance	1
Cisplatin	affects cotreatment, decreases expression	1
Clozapine	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	decreases expression, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651944	Binding	Binding affinity to human NUP160 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004402	PHASE3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00638820	PHASE2	TERMINATED	Reduced Intensity AlloTransplant For Osteopetrosis
NCT00968864	PHASE2	TERMINATED	T-cell Depleted Alternative Donor Transplantation
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02666768	PHASE2	COMPLETED	ACTIMMUNE in Intermediate Osteopetrosis
NCT00145886	PHASE1	TERMINATED	rhPTH Therapy for Low Turnover Bone Fragility
NCT00775931	PHASE2/PHASE3	COMPLETED	Allogeneic Transplantation For Severe Osteopetrosis
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT01087398	PHASE2/PHASE3	UNKNOWN	Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03301168	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
NCT00043329	Not specified	COMPLETED	Post Marketing Surveillance Study of Actimmune in Patients With Severe, Malignant Osteopetrosis
NCT00145587	Not specified	TERMINATED	Stem Cell Transplantation for Children Affected With Osteopetrosis
NCT01199094	Not specified	COMPLETED	Clinical Assessment of Patients With High Bone Mass Due to Mutation in Lrp5
NCT01200017	Not specified	NO_LONGER_AVAILABLE	Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT06521580	Not specified	COMPLETED	Outcomes of Patients With Osteopetrosis Weight-bearing Bone Fractures