NUP155

Summary

NUP155 (nucleoporin 155, HGNC:8063) is a protein-coding gene on chromosome 5p13.2, encoding Nuclear pore complex protein Nup155 (O75694). Essential component of nuclear pore complex. It is a common-essential gene (DepMap: required in 98.0% of cancer cell lines).

Nucleoporins are proteins that play an important role in the assembly and functioning of the nuclear pore complex (NPC) which regulates the movement of macromolecules across the nuclear envelope (NE). The protein encoded by this gene plays a role in the fusion of NE vesicles and formation of the double membrane NE. The protein may also be involved in cardiac physiology and may be associated with the pathogenesis of atrial fibrillation. Alternative splicing results in multiple transcript variants of this gene. A pseudogene associated with this gene is located on chromosome 6.

Source: NCBI Gene 9631 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial atrial fibrillation (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 303 total — 1 pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_153485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8063
Approved symbol	NUP155
Name	nucleoporin 155
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0791, N155
Ensembl gene	ENSG00000113569
Ensembl biotype	protein_coding
OMIM	606694
Entrez	9631

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000231498, ENST00000381843, ENST00000502533, ENST00000507233, ENST00000507675, ENST00000508182, ENST00000513532, ENST00000515054, ENST00000716591, ENST00000896264, ENST00000937458, ENST00000937459, ENST00000937460, ENST00000937461, ENST00000937462, ENST00000969937, ENST00000969938

RefSeq mRNA: 3 — MANE Select: NM_153485 NM_001278312, NM_004298, NM_153485

CCDS: CCDS3921, CCDS43310, CCDS64142

Canonical transcript exons

ENST00000231498 — 35 exons

Exon	Start	End
ENSE00000740858	37350160	37350265
ENSE00000740871	37358081	37358151
ENSE00000802037	37351190	37351356
ENSE00000802038	37352737	37352829
ENSE00001006235	37330038	37330132
ENSE00001006238	37317988	37318085
ENSE00001006241	37325901	37325967
ENSE00001006244	37337818	37337918
ENSE00001006249	37328358	37328420
ENSE00001006252	37314198	37314328
ENSE00001006255	37329190	37329278
ENSE00001006257	37331685	37331795
ENSE00001006258	37342549	37342646
ENSE00001006260	37310552	37310743
ENSE00001006262	37333463	37333633
ENSE00001006263	37323992	37324107
ENSE00001006264	37327629	37327776
ENSE00001006266	37341090	37341242
ENSE00001934728	37288137	37292038
ENSE00002024889	37370821	37371106
ENSE00003507859	37292879	37292985
ENSE00003516975	37302779	37302908
ENSE00003538131	37299448	37299568
ENSE00003552763	37305057	37305210
ENSE00003573738	37304739	37304843
ENSE00003585092	37363888	37363984
ENSE00003593411	37364247	37364384
ENSE00003619720	37309129	37309267
ENSE00003620856	37349172	37349245
ENSE00003621397	37307297	37307432
ENSE00003626197	37294329	37294465
ENSE00003644679	37298868	37298978
ENSE00003652591	37301437	37301550
ENSE00003665381	37303260	37303414
ENSE00003692507	37348505	37348596

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.1831 / max 673.0188, expressed in 1821 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61334	54.8618	1821
61335	0.6951	393
61337	0.5870	72
61336	0.0264	5
61338	0.0127	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.76	gold quality
male germ cell	CL:0000015	97.55	gold quality
left testis	UBERON:0004533	95.32	gold quality
right testis	UBERON:0004534	95.29	gold quality
testis	UBERON:0000473	93.91	gold quality
secondary oocyte	CL:0000655	91.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.30	gold quality
ventricular zone	UBERON:0003053	88.61	gold quality
adrenal tissue	UBERON:0018303	88.43	gold quality
adult organism	UBERON:0007023	88.37	gold quality
calcaneal tendon	UBERON:0003701	87.32	gold quality
embryo	UBERON:0000922	86.48	gold quality
ganglionic eminence	UBERON:0004023	86.43	gold quality
islet of Langerhans	UBERON:0000006	83.36	gold quality
bone marrow cell	CL:0002092	82.33	gold quality
stromal cell of endometrium	CL:0002255	82.27	gold quality
cortical plate	UBERON:0005343	81.90	gold quality
oocyte	CL:0000023	81.48	gold quality
bone marrow	UBERON:0002371	81.19	gold quality
esophagus squamous epithelium	UBERON:0006920	81.07	gold quality
tendon	UBERON:0000043	80.79	gold quality
skin of leg	UBERON:0001511	80.57	gold quality
colonic epithelium	UBERON:0000397	80.08	gold quality
skin of abdomen	UBERON:0001416	80.05	gold quality
rectum	UBERON:0001052	79.48	gold quality
zone of skin	UBERON:0000014	79.16	gold quality
pancreas	UBERON:0001264	78.75	gold quality
epithelium of esophagus	UBERON:0001976	78.69	gold quality
lymph node	UBERON:0000029	78.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.95
E-GEOD-124858	no	654.87
E-MTAB-10137	no	73.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, RBPJ

miRNA regulators (miRDB)

13 targeting NUP155, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-3622B-3P	96.82	66.36	988
HSA-MIR-3935	96.33	66.79	797

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• These human and mouse studies indicate that loss of NUP155 function causes atrial fibrillation by altering mRNA and protein transport and link the nuclear pore complex to cardiovascular disease. (PMID:19070573)
• The Nup155 depletion massively alters nuclear envelope structure, causing a dramatic decrease in Nuclear pore complexes numbers and the improper targeting of membrane proteins to the inner nuclear membrane. (PMID:20974814)
• The Nup155-mediated localization was required for HDAC4’s effect on gene expression. (PMID:21464227)
• lamin A/C mutation p.Arg399Cys weakens the interaction between nuclear lamina (lamin A/C) and the nuclear pore complex (NUP155), leading to the development of atrial fibrillation. (PMID:30488537)
• Study revealed that NUP155 controls mRNA translation CDKN1A, a key mediator of the p53 response. (PMID:31089132)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup155	ENSDARG00000001777
mus_musculus	Nup155	ENSMUSG00000022142
rattus_norvegicus	Nup155	ENSRNOG00000013411
drosophila_melanogaster	Nup154	FBGN0021761
caenorhabditis_elegans		WBGENE00003794

Protein

Protein identifiers

Nuclear pore complex protein Nup155 — O75694 (reviewed: O75694)

Alternative names: 155 kDa nucleoporin, Nucleoporin Nup155

All UniProt accessions (3): D6RA13, E9PF10, O75694

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of nuclear pore complex. Could be essessential for embryogenesis. Nucleoporins may be involved both in binding and translocating proteins during nucleocytoplasmic transport.

Subunit / interactions. Interacts with GLE1. Able to form a heterotrimer with GLE1 and NUP42 in vitro. Forms a complex with NUP35, NUP93, NUP205 and lamin B.

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

Tissue specificity. Expressed in all tissues tested, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Phosphorylated. Phosphorylation and dephosphorylation may be important for the function of NUP155 and may play a role in the reversible disassembly of the nuclear pore complex during mitosis. Disulfide-linked to NUP62. The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.

Disease relevance. Atrial fibrillation, familial, 15 (ATFB15) [MIM:615770] A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the non-repetitive/WGA-negative nucleoporin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75694-1	1	yes
O75694-2	2

RefSeq proteins (3): NP_001265241, NP_004289, NP_705618* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004870	Nucleoporin_Nup155	Family
IPR007187	Nucleoporin_Nup133/Nup155_C	Domain
IPR014908	Nucleoporin_Nup133/Nup155_N	Domain
IPR042533	Nucleoporin_Nup155_C_1	Homologous_superfamily
IPR042537	Nucleoporin_Nup155_C_2	Homologous_superfamily
IPR042538	Nucleoporin_Nup155_C_3	Homologous_superfamily

Pfam: PF03177, PF08801

UniProt features (77 total): strand 34, helix 24, turn 11, initiator methionine 1, chain 1, region of interest 1, modified residue 1, glycosylation site 1, cross-link 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7R1Y	ELECTRON MICROSCOPY	3
7EYE	ELECTRON MICROSCOPY	5.1
7EYF	ELECTRON MICROSCOPY	5.3
7EYQ	ELECTRON MICROSCOPY	5.4
7R5K	ELECTRON MICROSCOPY	12
5IJN	ELECTRON MICROSCOPY	21.4
5IJO	ELECTRON MICROSCOPY	21.4
5A9Q	ELECTRON MICROSCOPY	23
7PER	ELECTRON MICROSCOPY	35
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75694-F1	83.92	0.53

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 (2): 1057, 740

Glycosylation sites (1): 526

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: 339 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELL_CELL_SIGNALING, PATIL_LIVER_CANCER, GOBP_NUCLEAR_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, REACTOME_HIV_INFECTION, GOBP_MUSCLE_CONTRACTION, GOBP_CELL_COMMUNICATION_INVOLVED_IN_CARDIAC_CONDUCTION

GO Biological Process (12): transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery (GO:0000972), RNA export from nucleus (GO:0006405), mRNA export from nucleus (GO:0006406), protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), nuclear envelope organization (GO:0006998), miRNA processing (GO:0035196), protein localization to nuclear inner membrane (GO:0036228), atrial cardiac muscle cell action potential (GO:0086014), protein transport (GO:0015031), protein localization to nucleus (GO:0034504), mRNA transport (GO:0051028)

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

GO Cellular Component (7): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), nuclear pore inner ring (GO:0044611), 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
RNA transport	2
nuclear pore	2
nucleus	2
nuclear envelope	2
nuclear protein-containing complex	2
cellular anatomical structure	2
chromosome organization	1
nuclear export	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
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
regulatory ncRNA processing	1
protein localization to membrane	1
protein localization to nuclear envelope	1
cardiac muscle cell action potential involved in contraction	1
atrial cardiac muscle cell to AV node cell signaling	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein localization to organelle	1
structural molecule activity	1
nucleocytoplasmic transport	1
binding	1
endomembrane system	1
organelle envelope	1
cytoplasm	1
organelle membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP155	NUP35	Q8NFH5	996
NUP155	NUP205	Q92621	996
NUP155	NUP93	Q8N1F7	991
NUP155	NUP188	Q5SRE5	990
NUP155	NUP98	P52948	963
NUP155	NUP153	P49790	947
NUP155	WDR70	Q9NW82	939
NUP155	GLE1	Q53GS7	920
NUP155	RANBP2	P49792	919
NUP155	CPLANE1	Q9H799	915
NUP155	NUP107	P57740	908
NUP155	HDAC4	P56524	889
NUP155	NUP62	P37198	872
NUP155	NUP133	Q8WUM0	859
NUP155	NUP88	Q99567	859

IntAct

166 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LMNA	NUP155	psi-mi:“MI:0914”(association)	0.670
NUP155	LMNA	psi-mi:“MI:0914”(association)	0.670
NUP155	LMNA	psi-mi:“MI:0915”(physical association)	0.670
NUP155	LMNA	psi-mi:“MI:0403”(colocalization)	0.670
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
EFS	NUP155	psi-mi:“MI:0915”(physical association)	0.560
ALDH3B1	UBA6	psi-mi:“MI:0914”(association)	0.530
HOXB5	VPS37C	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
PNOC	NUP155	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
PDCD6IP	NUP155	psi-mi:“MI:0407”(direct interaction)	0.440
NUP155	Nup155	psi-mi:“MI:0915”(physical association)	0.400
AHCTF1	NUP155	psi-mi:“MI:0915”(physical association)	0.400
ZFYVE9	NUP155	psi-mi:“MI:0915”(physical association)	0.370
NUP155	GLE1	psi-mi:“MI:0915”(physical association)	0.370
Ranbp2	POM121C	psi-mi:“MI:0914”(association)	0.350

BioGRID (649): EFS (Two-hybrid), NUP155 (Affinity Capture-MS), NUP155 (Affinity Capture-MS), NUP155 (Affinity Capture-MS), NUP155 (Affinity Capture-MS), NUP155 (Affinity Capture-RNA), REG1B (Co-fractionation), NUP155 (Affinity Capture-MS), NUP155 (Proximity Label-MS), NUP155 (Proximity Label-MS), NUP155 (Affinity Capture-MS), NUP155 (Affinity Capture-MS), NUP155 (Proximity Label-MS), NUP155 (Proximity Label-MS), NUP155 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IC37, A1A4K3, A2CEI4, B1WC10, E9PY46, F1QEB7, F4IDS7, O08658, O13046, O75694, O75717, O95876, P33194, P37199, P59328, Q08D69, Q10569, Q10570, Q16531, Q32NR9, Q3U1J4, Q4ADV7, Q566H4, Q5DQR4, Q5R649, Q5U1Z0, Q5ZLG9, Q6P6Z0, Q6PGF3, Q6PJI9, Q7XWP1, Q802U2, Q805F9, Q8BMG7, Q8C0M0, Q8C456, Q8CEC0, Q8CJF7, Q8K1X1, Q8NFP9

Diamond homologs: O75694, P37199, Q99P88, Q9V463

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUP155	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 201 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
Signaling by ERBB2 ECD mutants	5	23.2×	3e-04
GRB2 events in ERBB2 signaling	5	21.9×	3e-04
VEGFR2 mediated cell proliferation	5	19.7×	4e-04
SHC1 events in ERBB2 signaling	5	16.4×	5e-04
Signaling by ERBB2 TMD/JMD mutants	5	16.4×	5e-04
Signaling by ERBB2 KD Mutants	5	14.6×	6e-04
Signaling by high-kinase activity BRAF mutants	6	13.1×	4e-04
MAP2K and MAPK activation	6	11.8×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	8	18.9×	3e-06
protein export from nucleus	5	14.3×	4e-03
cell surface receptor protein tyrosine kinase signaling pathway	13	12.7×	2e-08
protein autophosphorylation	13	10.6×	1e-07
mRNA export from nucleus	6	10.0×	5e-03
positive regulation of MAPK cascade	18	8.2×	1e-08
MAPK cascade	9	7.8×	6e-04
monoatomic ion transport	8	7.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	179
Likely benign	13
Benign	60

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
127142	NM_153485.3(NUP155):c.1172G>A (p.Arg391His)	Pathogenic

SpliceAI

4458 predictions. Top by Δscore:

Variant	Effect	Δscore
5:37291922:G:C	donor_gain	1.0000
5:37291942:C:A	donor_gain	1.0000
5:37291960:TGC:T	donor_gain	1.0000
5:37292878:CCTT:C	donor_gain	1.0000
5:37292917:T:C	donor_gain	1.0000
5:37294323:CCTTA:C	donor_loss	1.0000
5:37294324:CTTAC:C	donor_loss	1.0000
5:37294325:TTAC:T	donor_loss	1.0000
5:37294326:T:TG	donor_loss	1.0000
5:37294327:ACCCG:A	donor_loss	1.0000
5:37294328:C:A	donor_loss	1.0000
5:37294466:C:CC	acceptor_gain	1.0000
5:37298865:TA:T	donor_loss	1.0000
5:37298866:A:AT	donor_loss	1.0000
5:37298974:CAATT:C	acceptor_gain	1.0000
5:37298975:AATT:A	acceptor_gain	1.0000
5:37298975:AATTC:A	acceptor_loss	1.0000
5:37298976:ATT:A	acceptor_gain	1.0000
5:37298977:TT:T	acceptor_gain	1.0000
5:37298978:TCTGT:T	acceptor_loss	1.0000
5:37298979:C:A	acceptor_loss	1.0000
5:37298979:C:CC	acceptor_gain	1.0000
5:37298980:T:G	acceptor_loss	1.0000
5:37299564:TAAAG:T	acceptor_gain	1.0000
5:37299569:C:CC	acceptor_gain	1.0000
5:37301432:ATTAC:A	donor_loss	1.0000
5:37301434:TACC:T	donor_loss	1.0000
5:37301436:C:CA	donor_loss	1.0000
5:37301549:AC:A	acceptor_gain	1.0000
5:37301550:CC:C	acceptor_gain	1.0000

AlphaMissense

9134 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:37299469:A:G	W1221R	1.000
5:37299469:A:T	W1221R	1.000
5:37299516:A:T	I1205K	1.000
5:37299522:A:G	L1203P	1.000
5:37299552:G:T	A1193D	1.000
5:37325960:A:G	W678R	1.000
5:37325960:A:T	W678R	1.000
5:37327638:C:G	R672P	1.000
5:37327659:C:T	G665D	1.000
5:37327660:C:G	G665R	1.000
5:37330056:G:T	A569D	1.000
5:37330107:A:G	L552P	1.000
5:37341167:A:T	V390D	1.000
5:37363902:C:A	W126C	1.000
5:37363902:C:G	W126C	1.000
5:37363904:A:G	W126R	1.000
5:37363904:A:T	W126R	1.000
5:37363930:A:G	L117P	1.000
5:37363934:A:G	W116R	1.000
5:37363934:A:T	W116R	1.000
5:37299504:G:T	A1209D	0.999
5:37299516:A:C	I1205R	0.999
5:37299522:A:T	L1203H	0.999
5:37299567:A:G	L1188P	0.999
5:37299567:A:T	L1188H	0.999
5:37301465:A:G	L1178P	0.999
5:37302864:G:T	A1121D	0.999
5:37302865:C:G	A1121P	0.999
5:37302885:C:G	R1114P	0.999
5:37303272:G:T	A1102D	0.999

dbSNP variants (sampled 300 via entrez): RS1000010950 (5:37367852 C>T), RS1000031224 (5:37298099 C>T), RS1000046097 (5:37329871 A>G), RS1000073461 (5:37351563 C>T), RS1000104715 (5:37335806 G>A), RS1000128071 (5:37346784 G>A), RS1000183407 (5:37305889 A>C,G), RS1000261755 (5:37352942 G>A,T), RS1000273888 (5:37312163 C>A,G), RS1000299909 (5:37359329 C>A,T), RS1000399514 (5:37318124 C>T), RS1000456159 (5:37318546 C>T), RS1000460352 (5:37347289 T>C), RS1000500491 (5:37363188 A>G), RS1000534294 (5:37362962 G>C)

Disease associations

OMIM: gene MIM:606694 | disease phenotypes: MIM:615770

GenCC curated gene-disease

Disease	Classification	Inheritance
familial atrial fibrillation	Supportive	Autosomal dominant
atrial fibrillation, familial, 15	Limited	Autosomal recessive

Mondo (3): atrial fibrillation, familial, 15 (MONDO:0014340), premature menopause (MONDO:0001119), familial atrial fibrillation (MONDO:0018054)

Orphanet (0):

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001279	Syncope
HP:0001645	Sudden cardiac death
HP:0001658	Myocardial infarction
HP:0001727	Thromboembolic stroke
HP:0001907	Thromboembolism
HP:0001962	Palpitations
HP:0002094	Dyspnea
HP:0002321	Vertigo
HP:0003546	Exercise intolerance
HP:0003577	Congenital onset
HP:0004749	Atrial flutter
HP:0004755	Supraventricular tachycardia
HP:0005110	Atrial fibrillation
HP:0012378	Fatigue
HP:0031295	Left atrial enlargement
HP:0034197	Third trimester onset
HP:0100749	Chest pain

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010143_4	Meat-related diet	5.000000e-08
GCST010725_6	Malaria	9.000000e-07
GCST010725_66	Malaria	1.000000e-06
GCST010725_85	Malaria	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295680 (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
6.71	Kd	193.4	nM	CHEMBL5653589
6.71	ED50	193.4	nM	CHEMBL5653589
6.27	Kd	537.2	nM	CHEMBL3752910
6.27	ED50	537.2	nM	CHEMBL3752910
5.45	Kd	3547	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 12 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148901: Binding affinity to human NUP155 incubated for 45 mins by Kinobead based pull down assay	kd	0.1934	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148901: Binding affinity to human NUP155 incubated for 45 mins by Kinobead based pull down assay	kd	0.5372	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179184: Binding affinity against NUP155 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	3.5470	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, affects methylation	3
Valproic Acid	affects expression, decreases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Resveratrol	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
2-palmitoylglycerol	increases expression	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
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118654	Binding	Binding affinity to NUP155 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT04075994	Not specified	COMPLETED	Atrial Fibrillation Health Literacy and Information Technology Trial
NCT04076020	Not specified	COMPLETED	Atrial Fibrillation Health Literacy and Information Technology Trial in Rural Pennsylvania Counties
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure