NUP88

Summary

NUP88 (nucleoporin 88, HGNC:8067) is a protein-coding gene on chromosome 17p13.2, encoding Nuclear pore complex protein Nup88 (Q99567). Component of nuclear pore complex. It is a common-essential gene (DepMap: required in 98.7% 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, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 4927 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fetal akinesia deformation sequence 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 159 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 43
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_002532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8067
Approved symbol	NUP88
Name	nucleoporin 88
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC8530
Ensembl gene	ENSG00000108559
Ensembl biotype	protein_coding
OMIM	602552
Entrez	4927

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 24 protein_coding, 12 nonsense_mediated_decay, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000225696, ENST00000570937, ENST00000572019, ENST00000572290, ENST00000572809, ENST00000573169, ENST00000573584, ENST00000574087, ENST00000574855, ENST00000574867, ENST00000575976, ENST00000576708, ENST00000576862, ENST00000700529, ENST00000700530, ENST00000700531, ENST00000700532, ENST00000700533, ENST00000700534, ENST00000700535, ENST00000700536, ENST00000700537, ENST00000700538, ENST00000700539, ENST00000700540, ENST00000700541, ENST00000700542, ENST00000700543, ENST00000700544, ENST00000700545, ENST00000700546, ENST00000700547, ENST00000700548, ENST00000876646, ENST00000876647, ENST00000876648, ENST00000876649, ENST00000876650, ENST00000931554, ENST00000931555, ENST00000948887, ENST00000948888, ENST00000948889, ENST00000948890

RefSeq mRNA: 2 — MANE Select: NM_002532 NM_001320653, NM_002532

CCDS: CCDS11070, CCDS92236

Canonical transcript exons

ENST00000573584 — 17 exons

Exon	Start	End
ENSE00003464031	5387779	5387904
ENSE00003464227	5405057	5405243
ENSE00003470366	5394891	5394981
ENSE00003489891	5416513	5416682
ENSE00003497411	5414009	5414134
ENSE00003506450	5386708	5386826
ENSE00003513408	5399552	5399650
ENSE00003516433	5388802	5388960
ENSE00003528543	5410703	5410789
ENSE00003529339	5391561	5391662
ENSE00003640424	5386984	5387110
ENSE00003645291	5408733	5408909
ENSE00003651710	5387386	5387466
ENSE00003688009	5404099	5404246
ENSE00003688022	5387605	5387670
ENSE00003980066	5419354	5419662
ENSE00003980074	5384833	5386269

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6107 / max 208.0069, expressed in 1809 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164025	21.6107	1809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.23	gold quality
left testis	UBERON:0004533	98.12	gold quality
testis	UBERON:0000473	96.84	gold quality
oocyte	CL:0000023	96.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.86	gold quality
right lobe of liver	UBERON:0001114	95.73	gold quality
secondary oocyte	CL:0000655	95.40	gold quality
sperm	CL:0000019	95.04	gold quality
mucosa of transverse colon	UBERON:0004991	95.01	gold quality
left lobe of thyroid gland	UBERON:0001120	94.93	gold quality
ventricular zone	UBERON:0003053	94.85	gold quality
right lobe of thyroid gland	UBERON:0001119	94.73	gold quality
calcaneal tendon	UBERON:0003701	94.45	gold quality
tonsil	UBERON:0002372	94.43	gold quality
gastrocnemius	UBERON:0001388	94.42	gold quality
gingival epithelium	UBERON:0001949	94.38	gold quality
ganglionic eminence	UBERON:0004023	94.38	gold quality
adenohypophysis	UBERON:0002196	94.10	gold quality
cortical plate	UBERON:0005343	94.09	gold quality
thyroid gland	UBERON:0002046	94.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.03	gold quality
body of pancreas	UBERON:0001150	93.93	gold quality
gingiva	UBERON:0001828	93.90	gold quality
muscle of leg	UBERON:0001383	93.77	gold quality
male germ cell	CL:0000015	93.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.67	gold quality
rectum	UBERON:0001052	93.50	gold quality
adult organism	UBERON:0007023	93.36	gold quality
embryo	UBERON:0000922	93.25	gold quality
esophagus mucosa	UBERON:0002469	93.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.83
E-MTAB-6386	no	1158.49
E-GEOD-100618	no	604.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFAT5

miRNA regulators (miRDB)

42 targeting NUP88, 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-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-4473	98.89	69.10	652
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-1537-5P	98.70	68.33	999

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 22)

• High Nup88 mRNA expression levels correlated with ductal and tubular histology, nuclear grade 3, absence of hormone receptors, expression of c-erb-B2 oncogene and mutant p53 protein, high proliferation, DNA aneuploidy, and axillary node invasion. (PMID:14999780)
• A monoclonal antibody for Nup88 in an experimental model for studying the role played by Nup88 during cell development and differentiation. (PMID:15300515)
• the Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export (PMID:16675447)
• Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver. (PMID:17007055)
• The antitumor activity of deguelin was related to up-regulating the expression of Nup98 and down-regulating Nup88 protein. (PMID:17650673)
• Gambogic acid exerts its anti-leukemia effects by regulating the expression and distribution of nucleoporin Nup88. (PMID:17828493)
• The formation of high molecular mass complexes containing importin-alpha, Nup153 and Nup88 is increased upon oxidant treatment. (PMID:18068677)
• Nup88 is up-regulated in response to hypertonic stress and acts to retain TonEBP in the nucleus, activating transcription of critical osmoprotective genes. (PMID:18606815)
• Nup88 is significantly overexpressed in high-grade CIN lesions and ISCC compared with normal ectocervical squamous epithelia and CIN1. (PMID:19751906)
• proper expression of Nup88 is critical for preventing aneuploidy formation and tumorigenesis. (PMID:20497554)
• association found between myometrial invasion and Nup88 expression in endometrial carcinoma (PMID:20973273)
• Data suggest that a pool of Nup88 on the nuclear side of the nuclear pore complex provides a novel, unexpected binding site for nuclear lamin A. (PMID:21289091)
• Serum Nup88 might be a candidate for a new biomarker implicated in the development and aggressiveness of colorectal cancer (PMID:21863385)
• Nup88 mRNA was overexpressed in colorectal cancers and the overexpression was associated with cancer development and aggressiveness. (PMID:21896994)
• Nup62 and Nup88 protein levels were significantly decreased upon knockdown of O-GlcNAc transferase. (PMID:23777819)
• These findings demonstrate that the NUP88-NUP98-RAE1-APC/CCDH1 axis contributes to aneuploidy (PMID:26731471)
• Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions (PMID:26839161)
• Overexpression of the NUP88 is associated with cancer. (PMID:27636375)
• Study in HeLa cells revealed that Nup88 can affect the phosphorylation status of vimentin, which may contribute to the Nup88-dependent multinucleated phenotype through changing the organization of vimentin. (PMID:29724197)
• Here we report biallelic mutations in the nucleoporin NUP88 as a novel cause of lethal fetal akinesia deformation sequence (FADS) in two families. We demonstrate that NUP88 depletion affects rapsyn, a key regulator of the muscle nicotinic acetylcholine receptor at the neuromuscular junction. (PMID:30543681)
• Loss of Nup88 inhibited nuclear export of recombination signal-binding protein for immunoglobulin kappaJ region (RBP-J), the DNA-binding component of the Notch pathway. (PMID:31186352)
• Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells. (PMID:34331103)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup88	ENSDARG00000003235
mus_musculus	Nup88	ENSMUSG00000040667
rattus_norvegicus	Nup88	ENSRNOG00000006126
drosophila_melanogaster	mbo	FBGN0026207

Protein

Protein identifiers

Nuclear pore complex protein Nup88 — Q99567 (reviewed: Q99567)

Alternative names: 88 kDa nucleoporin, Nucleoporin Nup88

All UniProt accessions (24): Q99567, A0A8V8TPS0, A0A8V8TPS5, A0A8V8TPT0, A0A8V8TPT4, A0A8V8TQA5, A0A8V8TQB1, A0A8V8TQB7, A0A8V8TQC2, A0A8V8TQC3, A0A8V8TQC7, A0A8V8TQD1, A0A8V8TQD5, A0A8V8TQZ0, A0A8V8TQZ4, A0A8V8TQZ7, A0A8V8TR00, A0A8V8TRA1, A0A8V8TRA5, A0A8V8TRA7, I3L245, I3L2W3, I3L4K7, J3KMX1

UniProt curated annotations — full annotation on UniProt →

Function. Component of nuclear pore complex.

Subunit / interactions. Interacts with NUP214/CAN. Interacts with NUP62 and NUP98.

Subcellular location. Nucleus. Nuclear pore complex.

Tissue specificity. Ubiquitous.

Disease relevance. Fetal akinesia deformation sequence 4 (FADS4) [MIM:618393] A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS4 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Disease mechanism likely includes impaired formation of the neuromuscular junction. NUP88 silencing in vitro results in reduced levels of rapsyn, a key player in clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. Decreased rapsyn levels have also been observed in a patient muscle biopsy.

RefSeq proteins (2): NP_001307582, NP_002523* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019321	Nucleoporin_Nup88	Family
IPR037700	NUP88/NUP82	Family

Pfam: PF10168

UniProt features (68 total): strand 33, modified residue 10, helix 8, turn 6, sequence variant 4, sequence conflict 4, initiator methionine 1, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MNI	X-RAY DIFFRACTION	2
7R5K	ELECTRON MICROSCOPY	12
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99567-F1	80.02	0.42

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 (10): 525, 540, 698, 2, 35, 50, 379, 437, 442, 517

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: 0 (showing top):

GO Biological Process (7): ribosomal large subunit export from nucleus (GO:0000055), ribosomal small subunit export from nucleus (GO:0000056), mRNA export from nucleus (GO:0006406), protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), 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 (5): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytosol (GO:0005829), 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
ribosomal subunit export from nucleus	2
cellular anatomical structure	2
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
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
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
nuclear protein-containing complex	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP88	NUP214	P35658	998
NUP88	RANBP2	P49792	993
NUP88	NUP98	P52948	979
NUP88	NUP62	P37198	977
NUP88	RGPD1	P0C839	976
NUP88	NUP153	P49790	963
NUP88	XPO1	O14980	956
NUP88	NUP85	Q9BW27	948
NUP88	NUP93	Q8N1F7	884
NUP88	NUP205	Q92621	876
NUP88	AAAS	Q9NRG9	869
NUP88	NUP50	Q9UKX7	868
NUP88	NUP107	P57740	867
NUP88	NUP155	O75694	859
NUP88	NUP160	Q12769	859

IntAct

108 interactions, top by confidence:

A	B	Type	Score
DDX19A	MIF4GD	psi-mi:“MI:0914”(association)	0.860
NXF1	NUP214	psi-mi:“MI:0914”(association)	0.810
NUP62	NUP88	psi-mi:“MI:0915”(physical association)	0.800
NUP214	NUP88	psi-mi:“MI:0915”(physical association)	0.740
NUP88	NUP214	psi-mi:“MI:0914”(association)	0.740
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NUP88	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
NUP88	XPO1	psi-mi:“MI:0914”(association)	0.530
Nup214	OGT	psi-mi:“MI:0915”(physical association)	0.400
Nup88		psi-mi:“MI:0915”(physical association)	0.400
Stn1	CTC1	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
NUP88	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
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
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

BioGRID (208): NUP88 (Affinity Capture-MS), NUP88 (Affinity Capture-MS), NUP88 (Affinity Capture-MS), NUP88 (Affinity Capture-MS), NUP62 (Co-fractionation), NUP88 (Co-fractionation), NUP88 (Co-fractionation), RBM42 (Co-fractionation), NUP88 (Affinity Capture-MS), NUP88 (Affinity Capture-MS), NUP88 (Proximity Label-MS), NUP88 (Proximity Label-MS), NUP88 (Proximity Label-MS), NUP88 (Affinity Capture-MS), NUP88 (Affinity Capture-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: A2CEI4, O08658, Q8CEC0, Q99567

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUP88	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
Rev-mediated nuclear export of HIV RNA	11	45.3×	1e-13
NEP/NS2 Interacts with the Cellular Export Machinery	10	44.9×	2e-12
Nuclear import of Rev protein	10	43.6×	2e-12
Transport of the SLBP independent Mature mRNA	10	42.4×	2e-12
Transport of Ribonucleoproteins into the Host Nucleus	9	41.7×	2e-11
Transport of the SLBP Dependant Mature mRNA	10	41.2×	2e-12
IPs transport between nucleus and cytosol	8	39.5×	5e-10
IP3 and IP4 transport between cytosol and nucleus	8	39.5×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	5	45.5×	9e-06
nucleocytoplasmic transport	10	38.0×	6e-11
mRNA transport	10	25.6×	2e-09
protein export from nucleus	5	24.8×	2e-04
mRNA export from nucleus	7	20.1×	9e-06
autophagosome maturation	5	17.0×	9e-04
mitophagy	5	15.4×	1e-03
protein import into nucleus	11	15.4×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	107
Likely benign	15
Benign	10

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
625468	NM_002532.6(NUP88):c.1300G>T (p.Asp434Tyr)	Pathogenic
625469	NM_002532.6(NUP88):c.1525C>T (p.Arg509Ter)	Pathogenic
625470	NM_002532.6(NUP88):c.1899_1901del (p.Glu634del)	Pathogenic
4845740	NM_002532.6(NUP88):c.322_323del (p.Leu108fs)	Likely pathogenic

SpliceAI

4475 predictions. Top by Δscore:

Variant	Effect	Δscore
17:5365099:AATT:A	acceptor_gain	1.0000
17:5365110:A:AG	acceptor_gain	1.0000
17:5365110:AAAAT:A	acceptor_gain	1.0000
17:5365112:A:G	acceptor_gain	1.0000
17:5365114:T:G	acceptor_gain	1.0000
17:5365118:A:AG	acceptor_gain	1.0000
17:5365119:CAGGT:C	acceptor_loss	1.0000
17:5365120:A:AG	acceptor_gain	1.0000
17:5365120:AG:A	acceptor_gain	1.0000
17:5365120:AGGT:A	acceptor_gain	1.0000
17:5365121:G:GG	acceptor_gain	1.0000
17:5365121:G:GT	acceptor_loss	1.0000
17:5365121:GG:G	acceptor_gain	1.0000
17:5365121:GGT:G	acceptor_gain	1.0000
17:5365121:GGTG:G	acceptor_gain	1.0000
17:5365121:GGTGA:G	acceptor_gain	1.0000
17:5365235:CCAG:C	donor_gain	1.0000
17:5365235:CCAGG:C	donor_loss	1.0000
17:5365236:CAGGT:C	donor_loss	1.0000
17:5365237:AGGTA:A	donor_loss	1.0000
17:5365238:GGTAA:G	donor_loss	1.0000
17:5365239:G:GG	donor_gain	1.0000
17:5365239:GTAAG:G	donor_loss	1.0000
17:5365240:T:A	donor_loss	1.0000
17:5368354:ATGT:A	acceptor_gain	1.0000
17:5368355:T:G	acceptor_gain	1.0000
17:5368366:A:AG	acceptor_gain	1.0000
17:5368367:A:AG	acceptor_gain	1.0000
17:5368367:AAG:A	acceptor_loss	1.0000
17:5368368:A:AG	acceptor_gain	1.0000

AlphaMissense

4840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:5405183:G:C	N306K	0.999
17:5405183:G:T	N306K	0.999
17:5405091:A:T	V337D	0.998
17:5414070:A:G	W178R	0.998
17:5414070:A:T	W178R	0.998
17:5399596:A:T	V416D	0.997
17:5399630:A:C	Y405D	0.997
17:5404197:A:T	V365E	0.997
17:5404203:A:G	L363P	0.997
17:5405093:A:C	C336W	0.997
17:5405095:A:G	C336R	0.997
17:5387417:C:G	A629P	0.996
17:5405182:A:G	Y307H	0.996
17:5405188:C:G	D305H	0.995
17:5405199:G:T	P301H	0.995
17:5408769:C:A	G274V	0.995
17:5408877:G:T	A238E	0.995
17:5399585:A:G	W420R	0.994
17:5399585:A:T	W420R	0.994
17:5405200:G:A	P301S	0.994
17:5405205:A:T	M299K	0.994
17:5408788:A:C	Y268D	0.994
17:5410785:A:C	Y200D	0.994
17:5387447:C:G	A619P	0.993
17:5404179:A:G	L371S	0.993
17:5405094:C:T	C336Y	0.993
17:5405182:A:C	Y307D	0.993
17:5405205:A:C	M299R	0.993
17:5405205:A:G	M299T	0.993
17:5405211:A:G	L297S	0.993

dbSNP variants (sampled 300 via entrez): RS1000002315 (17:5390875 T>C), RS1000036659 (17:5393683 A>G,T), RS1000044100 (17:5388483 T>C,G), RS1000112313 (17:5396308 C>A,T), RS1000189693 (17:5397605 A>T), RS1000357450 (17:5407325 A>C), RS1000383589 (17:5410846 A>G), RS1000407827 (17:5401063 C>T), RS1000442223 (17:5404647 T>C), RS1000512462 (17:5400407 A>G), RS1000530647 (17:5389485 C>T), RS1000627053 (17:5400200 T>C), RS1000649578 (17:5389691 G>A), RS1000807869 (17:5405731 C>T), RS1000913998 (17:5400449 T>C)

Disease associations

OMIM: gene MIM:602552 | disease phenotypes: MIM:618393

GenCC curated gene-disease

Disease	Classification	Inheritance
fetal akinesia deformation sequence 4	Strong	Autosomal recessive
fetal akinesia deformation sequence 1	Supportive	Autosomal recessive

Mondo (2): fetal akinesia deformation sequence 4 (MONDO:0100104), fetal akinesia deformation sequence 1 (MONDO:0100101)

Orphanet (0):

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000476	Cystic hygroma
HP:0000878	11 pairs of ribs
HP:0001059	Pterygium
HP:0001262	Excessive daytime somnolence
HP:0001305	Dandy-Walker malformation
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001838	Rocker bottom foot
HP:0001989	Fetal akinesia sequence
HP:0002089	Pulmonary hypoplasia
HP:0002093	Respiratory insufficiency
HP:0002304	Akinesia
HP:0002375	Hypokinesia
HP:0002650	Scoliosis
HP:0002804	Arthrogryposis multiplex congenita
HP:0002808	Kyphosis
HP:0002828	Multiple joint contractures

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010988_55	Adult body size	1.000000e-11
GCST90002388_484	Lymphocyte count	5.000000e-10
GCST90002395_239	Mean platelet volume	1.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	5
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	decreases expression	2
nickel sulfate	increases expression	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	decreases expression	1
diethyl maleate	affects cotreatment, increases glycosylation, increases phosphorylation, affects localization, affects reaction	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, affects reaction, affects cotreatment	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects reaction, affects cotreatment, affects localization	1
deguelin	decreases expression	1
monomethylarsonous acid	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
dimethylarsinous acid	decreases expression	1
pyrimidifen	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Dinitrochlorobenzene	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Eugenol	increases expression	1
Formaldehyde	decreases expression	1

Clinical trials (associated diseases)

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