NUP50

Summary

NUP50 (nucleoporin 50, HGNC:8065) is a protein-coding gene on chromosome 22q13.31, encoding Nuclear pore complex protein Nup50 (Q9UKX7). Component of the nuclear pore complex that has a direct role in nuclear protein import. It is a selective cancer dependency (DepMap: 53.8% 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 that functions as a soluble cofactor in importin-alpha:beta-mediated nuclear protein import. Pseudogenes of this gene are found on chromosomes 5, 6, and 14. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10762 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Limited, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 53.8% of screened cell lines
• MANE Select transcript: NM_007172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8065
Approved symbol	NUP50
Name	nucleoporin 50
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000093000
Ensembl biotype	protein_coding
OMIM	604646
Entrez	10762

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 18 protein_coding, 6 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000347635, ENST00000396096, ENST00000407019, ENST00000417702, ENST00000419387, ENST00000422489, ENST00000424634, ENST00000430547, ENST00000432340, ENST00000434760, ENST00000445721, ENST00000461194, ENST00000461437, ENST00000469163, ENST00000484186, ENST00000486184, ENST00000491860, ENST00000493456, ENST00000497960, ENST00000872922, ENST00000872923, ENST00000872924, ENST00000913935, ENST00000913936, ENST00000913937, ENST00000946230, ENST00000946231, ENST00000946232

RefSeq mRNA: 2 — MANE Select: NM_007172 NM_007172, NM_153645

CCDS: CCDS14062, CCDS14063

Canonical transcript exons

ENST00000347635 — 8 exons

Exon	Start	End
ENSE00001185148	45163925	45164296
ENSE00001300233	45184453	45188017
ENSE00003464927	45175894	45176080
ENSE00003477842	45178238	45178900
ENSE00003506930	45183402	45183520
ENSE00003524211	45168168	45168246
ENSE00003558957	45171600	45171683
ENSE00003618313	45181286	45181367

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4133 / max 44.5915, expressed in 1608 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192701	4.4133	1608

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	97.61	gold quality
cervix squamous epithelium	UBERON:0006922	96.23	gold quality
nasal cavity epithelium	UBERON:0005384	95.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.63	gold quality
tongue squamous epithelium	UBERON:0006919	95.47	gold quality
bone marrow	UBERON:0002371	95.38	gold quality
bone marrow cell	CL:0002092	94.61	gold quality
endothelial cell	CL:0000115	94.23	gold quality
trabecular bone tissue	UBERON:0002483	94.19	gold quality
choroid plexus epithelium	UBERON:0003911	93.99	gold quality
blood	UBERON:0000178	93.92	gold quality
sperm	CL:0000019	93.85	gold quality
squamous epithelium	UBERON:0006914	93.81	gold quality
oviduct epithelium	UBERON:0004804	93.77	gold quality
adrenal tissue	UBERON:0018303	93.74	gold quality
middle temporal gyrus	UBERON:0002771	93.39	gold quality
nasal cavity mucosa	UBERON:0001826	93.23	gold quality
secondary oocyte	CL:0000655	93.22	gold quality
monocyte	CL:0000576	93.18	gold quality
esophagus squamous epithelium	UBERON:0006920	93.18	gold quality
tonsil	UBERON:0002372	93.02	gold quality
leukocyte	CL:0000738	92.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.96	gold quality
mononuclear cell	CL:0000842	92.95	gold quality
colonic mucosa	UBERON:0000317	92.95	gold quality
ventricular zone	UBERON:0003053	92.91	gold quality
buccal mucosa cell	CL:0002336	92.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.67	gold quality
gingival epithelium	UBERON:0001949	92.60	gold quality
gingiva	UBERON:0001828	92.40	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-81383	no	572.82
E-MTAB-8060	no	167.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

195 targeting NUP50, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Results suggest that Npap60L and Npap60S function differently in nuclear protein import. (PMID:20016008)
• Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin alpha5. (PMID:22130666)
• analysis of the Nup153-Nup50 protein interface and its role in nuclear import (PMID:23007389)
• results further highlight the antagonistic relationship between 53BP1 and BRCA1, and place Nup153 and Nup50 in a molecular pathway that regulates 53BP1 function by counteracting BRCA1-mediated events. (PMID:28751496)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup50	ENSDARG00000017454
mus_musculus	Nup50	ENSMUSG00000016619
mus_musculus	Nup50l	ENSMUSG00000072878
rattus_norvegicus	Nup50	ENSRNOG00000013423
rattus_norvegicus	Nup50-ps1	ENSRNOG00000024560
drosophila_melanogaster	Nup50	FBGN0033264
caenorhabditis_elegans		WBGENE00003802

Protein

Protein identifiers

Nuclear pore complex protein Nup50 — Q9UKX7 (reviewed: Q9UKX7)

Alternative names: 50 kDa nucleoporin, Nuclear pore-associated protein 60 kDa-like, Nucleoporin Nup50

All UniProt accessions (7): Q9UKX7, A0A0G2JI20, A0A0G2JIF9, B0QY21, B1AHA5, F2Z3L9, X6RKQ2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the nuclear pore complex that has a direct role in nuclear protein import. Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling. Interacts with regulatory proteins of cell cycle progression including CDKN1B. This interaction is required for correct intracellular transport and degradation of CDKN1B.

Subunit / interactions. Interacts with Importin alpha-2, Importin beta, Importin beta-2, NUP153, Ran binding protein 7, CDKN1B and itself. Does not interact with TPR.

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

Tissue specificity. Ubiquitous. Highest levels in testis, peripheral blood leukocytes and fetal liver.

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

Miscellaneous. Contrarily to Npap60L, Npap60S does not displaces NLSs, but stabilizes their binding to importin-alpha.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKX7-1	1, Npap60L	yes
Q9UKX7-2	2, Npap60S

RefSeq proteins (2): NP_009103, NP_705931 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000156	Ran_bind_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015007	NUP2/50/61	Domain
IPR045255	RanBP1-like	Family

Pfam: PF00638, PF08911

UniProt features (50 total): modified residue 13, strand 10, region of interest 7, repeat 5, compositionally biased region 4, turn 3, helix 2, chain 1, cross-link 1, splice variant 1, sequence conflict 1, initiator methionine 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MO0	X-RAY DIFFRACTION	2.45
3TJ3	X-RAY DIFFRACTION	2.7
2EC1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKX7-F1	65.90	0.32

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 (14): 8, 52, 83, 127, 208, 221, 234, 246, 259, 270, 296, 450, 353, 2

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

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

MSigDB gene sets: 330 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MODULE_52, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, YAGI_AML_WITH_INV_16_TRANSLOCATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_NEURAL_TUBE_DEVELOPMENT, MODULE_16, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (6): neural tube formation (GO:0001841), protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), mRNA transport (GO:0051028), protein transport (GO:0015031), intracellular transport (GO:0046907)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), nuclear membrane (GO:0031965), nucleus (GO:0005634), membrane (GO:0016020)

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
transport	2
nucleus	2
nuclear envelope	2
cellular anatomical structure	2
embryonic epithelial tube formation	1
neural tube development	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
nuclear transport	1
RNA transport	1
intracellular protein localization	1
establishment of protein localization	1
intracellular anatomical structure	1
cellular localization	1
establishment of localization in cell	1
binding	1
endomembrane system	1
organelle envelope	1
nuclear protein-containing complex	1
nuclear lumen	1
organelle membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP50	NUP153	P49790	996
NUP50	TPR	P12270	895
NUP50	NUP62	P37198	895
NUP50	AHCTF1	Q8WYP5	876
NUP50	NUP98	P52948	873
NUP50	NUP88	Q99567	868
NUP50	NUP107	P57740	854
NUP50	NUP93	Q8N1F7	851
NUP50	NUP58	Q9BVL2	846
NUP50	NUP54	Q7Z3B4	839
NUP50	NUP214	P35658	809
NUP50	NUP133	Q8WUM0	805
NUP50	NUP155	O75694	798
NUP50	SEH1L	Q96EE3	797
NUP50	NUP43	Q8NFH3	789

IntAct

164 interactions, top by confidence:

A	B	Type	Score
KPNA1	NUP50	psi-mi:“MI:0915”(physical association)	0.930
NUP50	KPNA1	psi-mi:“MI:0915”(physical association)	0.930
NUP50	KPNA6	psi-mi:“MI:0915”(physical association)	0.870
NUP50	KPNA2	psi-mi:“MI:0915”(physical association)	0.870
KPNA2	NUP50	psi-mi:“MI:0915”(physical association)	0.870
KPNA6	NUP50	psi-mi:“MI:0915”(physical association)	0.870
NUP50	KPNA4	psi-mi:“MI:0915”(physical association)	0.830
KPNA5	NUP50	psi-mi:“MI:0915”(physical association)	0.830
KPNA4	NUP50	psi-mi:“MI:0915”(physical association)	0.830
NUP50	KPNA5	psi-mi:“MI:0915”(physical association)	0.830
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
KPNA2	NUP153	psi-mi:“MI:0914”(association)	0.790
NUP50	KPNA3	psi-mi:“MI:0915”(physical association)	0.780
KPNA3	NUP50	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (485): NUP50 (Two-hybrid), NUP50 (Two-hybrid), NUP50 (Two-hybrid), NUP50 (Two-hybrid), NUP50 (Two-hybrid), KPNA6 (Two-hybrid), TP53BP1 (Affinity Capture-MS), PHF10 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), SMARCC2 (Affinity Capture-MS), BOD1L1 (Affinity Capture-MS), ARID2 (Affinity Capture-MS), KPNA5 (Affinity Capture-MS), KPNA6 (Affinity Capture-MS), KPNA1 (Affinity Capture-MS)

ESM2 similar proteins: E9Q3G8, O08587, O15117, O15504, O35601, O60318, O60934, P32499, P33215, P35658, P42566, P42567, P49790, P49791, Q15054, Q3B7M6, Q3MHS2, Q4ADK7, Q4R4T9, Q5EAW4, Q5FVW4, Q5R4Y2, Q5RB98, Q5VT52, Q5XGN1, Q5ZI22, Q5ZK28, Q640Z6, Q6P0U9, Q6PFD9, Q6PFK1, Q6XV80, Q75UQ2, Q7K0D8, Q80U93, Q8CIC2, Q8HXY9, Q8NHV4, Q8R1N0, Q9C829

Diamond homologs: O08587, Q7K0D8, Q9JIH2, Q9UKX7

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
MAPK3	“down-regulates activity”	NUP50	phosphorylation
CDK1	down-regulates	NUP50	phosphorylation
ERK1/2	“down-regulates activity”	NUP50	phosphorylation
MAPK1	“down-regulates activity”	NUP50	phosphorylation
MAPK3	down-regulates	NUP50	phosphorylation
Gbeta	down-regulates	NUP50	phosphorylation
NUP50	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NS1 Mediated Effects on Host Pathways	11	33.4×	6e-12
Nuclear import of Rev protein	8	28.6×	3e-08
Transport of Ribonucleoproteins into the Host Nucleus	7	26.6×	5e-07
Transport of the SLBP independent Mature mRNA	7	24.3×	7e-07
Transport of the SLBP Dependant Mature mRNA	7	23.6×	7e-07
NEP/NS2 Interacts with the Cellular Export Machinery	6	22.1×	9e-06
Vpr-mediated nuclear import of PICs	6	21.4×	1e-05
Transport of Mature mRNA Derived from an Intronless Transcript	7	20.2×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	8	53.5×	4e-10
RNA export from nucleus	5	39.0×	2e-05
alternative mRNA splicing, via spliceosome	5	28.1×	1e-04
protein import into nucleus	19	22.8×	6e-18
mRNA transport	8	17.6×	5e-06
nucleocytoplasmic transport	5	16.3×	1e-03
mRNA stabilization	5	15.3×	1e-03
positive regulation of transcription elongation by RNA polymerase II	6	15.1×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1600 predictions. Top by Δscore:

Variant	Effect	Δscore
22:45168161:A:AG	acceptor_gain	1.0000
22:45168163:CTTAG:C	acceptor_loss	1.0000
22:45168165:TAG:T	acceptor_loss	1.0000
22:45168167:GGTTC:G	acceptor_gain	1.0000
22:45168243:AGAGG:A	donor_loss	1.0000
22:45168244:GAG:G	donor_gain	1.0000
22:45168244:GAGGT:G	donor_loss	1.0000
22:45168245:AGGTA:A	donor_loss	1.0000
22:45168246:GG:G	donor_loss	1.0000
22:45168248:T:A	donor_loss	1.0000
22:45171594:TTGCA:T	acceptor_loss	1.0000
22:45171595:TGCAG:T	acceptor_loss	1.0000
22:45171596:GCAGG:G	acceptor_loss	1.0000
22:45171597:CAGGT:C	acceptor_loss	1.0000
22:45171598:A:G	acceptor_loss	1.0000
22:45171599:G:C	acceptor_loss	1.0000
22:45171681:GAA:G	donor_gain	1.0000
22:45171683:AGTG:A	donor_loss	1.0000
22:45171684:G:GG	donor_gain	1.0000
22:45171684:G:T	donor_loss	1.0000
22:45171685:T:A	donor_loss	1.0000
22:45171686:GAGT:G	donor_loss	1.0000
22:45175892:A:AG	acceptor_gain	1.0000
22:45175892:AGTCT:A	acceptor_gain	1.0000
22:45175893:G:GG	acceptor_gain	1.0000
22:45175893:GTCT:G	acceptor_gain	1.0000
22:45175893:GTCTG:G	acceptor_gain	1.0000
22:45176080:GGTA:G	donor_loss	1.0000
22:45176081:GTAA:G	donor_loss	1.0000
22:45176082:T:G	donor_loss	1.0000

AlphaMissense

3079 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:45168189:A:C	R4S	0.999
22:45168189:A:T	R4S	0.999
22:45168222:G:C	W15C	0.999
22:45168222:G:T	W15C	0.999
22:45183452:G:A	G379D	0.999
22:45183458:T:C	L381P	0.999
22:45183494:T:C	L393P	0.999
22:45183503:G:C	R396P	0.999
22:45184519:T:A	V424D	0.999
22:45168188:G:C	R4T	0.998
22:45168220:T:A	W15R	0.998
22:45168220:T:C	W15R	0.998
22:45171609:T:C	F27L	0.998
22:45171611:C:A	F27L	0.998
22:45171611:C:G	F27L	0.998
22:45171644:A:C	R38S	0.998
22:45171644:A:T	R38S	0.998
22:45183403:T:C	C363R	0.998
22:45183451:G:C	G379R	0.998
22:45184465:T:C	L406P	0.998
22:45184591:G:C	R448P	0.998
22:45168186:A:C	K3N	0.997
22:45168186:A:T	K3N	0.997
22:45168206:T:C	L10P	0.997
22:45178385:T:C	L163S	0.997
22:45178409:T:A	I171K	0.997
22:45183410:T:C	L365P	0.997
22:45183464:T:C	L383S	0.997
22:45183500:T:A	V395E	0.997
22:45171643:G:C	R38T	0.996

dbSNP variants (sampled 300 via entrez): RS1000043278 (22:45184712 TAAAGTTAGTC>T), RS1000229452 (22:45168370 A>G), RS1000349013 (22:45178921 T>C), RS1000352587 (22:45163358 C>G,T), RS1000401397 (22:45179126 A>C,G,T), RS1000528338 (22:45184230 C>A,G), RS1000564954 (22:45187487 C>T), RS1000570107 (22:45169259 A>G), RS1000631371 (22:45188470 G>A,T), RS1000635771 (22:45162317 G>A), RS1000738060 (22:45180460 A>G), RS1000783651 (22:45164224 G>T), RS1000797933 (22:45174187 T>C), RS1000806949 (22:45163112 G>A), RS1000914832 (22:45174508 T>C)

Disease associations

OMIM: gene MIM:604646 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	AD

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002392_229	Mean corpuscular volume	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067071 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.30	Kd	50.59	nM	CHEMBL5653589
7.30	ED50	50.59	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148906: Binding affinity to human NUP50 incubated for 45 mins by Kinobead based pull down assay	kd	0.0506	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	affects sumoylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
cylindrospermopsin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Antimycin A	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Benztropine	increases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	increases expression	1
Clozapine	increases expression	1
Coumestrol	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	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
CHEMBL5651948	Binding	Binding affinity to human NUP50 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)

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