RAE1

Summary

RAE1 (ribonucleic acid export 1, HGNC:9828) is a protein-coding gene on chromosome 20q13.31, encoding mRNA export factor RAE1 (P78406). Acts as a mRNA export factor involved in nucleocytoplasmic transport. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

Mutations in the Schizosaccharomyces pombe Rae1 and Saccharomyces cerevisiae Gle2 genes have been shown to result in accumulation of poly(A)-containing mRNA in the nucleus, suggesting that the encoded proteins are involved in RNA export. The protein encoded by this gene is a homolog of yeast Rae1. It contains four WD40 motifs, and has been shown to localize to distinct foci in the nucleoplasm, to the nuclear rim, and to meshwork-like structures throughout the cytoplasm. This gene is thought to be involved in nucleocytoplasmic transport, and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 8480 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_003610

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9828
Approved symbol	RAE1
Name	ribonucleic acid export 1
Location	20q13.31
Locus type	gene with protein product
Status	Approved
Aliases	Mnrp41, Gle2
Ensembl gene	ENSG00000101146
Ensembl biotype	protein_coding
OMIM	603343
Entrez	8480

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000371242, ENST00000395840, ENST00000395841, ENST00000411894, ENST00000429339, ENST00000452119, ENST00000462438, ENST00000492498, ENST00000527947, ENST00000857607, ENST00000922549, ENST00000922550, ENST00000947294, ENST00000947295

RefSeq mRNA: 2 — MANE Select: NM_003610 NM_001015885, NM_003610

CCDS: CCDS13458

Canonical transcript exons

ENST00000395841 — 12 exons

Exon	Start	End
ENSE00000662941	57354712	57354816
ENSE00000845744	57356446	57356538
ENSE00000907050	57365356	57365442
ENSE00000907051	57366807	57366893
ENSE00000907052	57367008	57367079
ENSE00000907053	57368705	57368812
ENSE00000907054	57373475	57373581
ENSE00001454763	57351255	57351422
ENSE00002186563	57354032	57354128
ENSE00003469125	57374607	57374801
ENSE00003653699	57373663	57373738
ENSE00003845672	57378013	57379202

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.9824 / max 288.6944, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185467	53.7838	1824
185469	0.1661	4
185468	0.0228	8
185470	0.0098	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.73	gold quality
sperm	CL:0000019	97.79	gold quality
oocyte	CL:0000023	97.75	gold quality
endometrium epithelium	UBERON:0004811	97.24	gold quality
male germ cell	CL:0000015	97.11	gold quality
adult organism	UBERON:0007023	96.50	gold quality
left testis	UBERON:0004533	96.47	gold quality
right testis	UBERON:0004534	96.41	gold quality
testis	UBERON:0000473	95.86	gold quality
tendon of biceps brachii	UBERON:0008188	94.14	gold quality
medial globus pallidus	UBERON:0002477	93.68	gold quality
embryo	UBERON:0000922	93.58	gold quality
trabecular bone tissue	UBERON:0002483	93.46	gold quality
cortical plate	UBERON:0005343	92.76	gold quality
ganglionic eminence	UBERON:0004023	92.63	gold quality
bone marrow	UBERON:0002371	92.54	gold quality
ventricular zone	UBERON:0003053	92.48	gold quality
amniotic fluid	UBERON:0000173	92.16	gold quality
oral cavity	UBERON:0000167	92.06	gold quality
cervix squamous epithelium	UBERON:0006922	91.88	silver quality
globus pallidus	UBERON:0001875	91.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.72	gold quality
endothelial cell	CL:0000115	91.64	gold quality
penis	UBERON:0000989	91.38	gold quality
squamous epithelium	UBERON:0006914	91.20	gold quality
esophagus squamous epithelium	UBERON:0006920	91.02	gold quality
epithelium of esophagus	UBERON:0001976	90.78	gold quality
parotid gland	UBERON:0001831	90.48	gold quality
gingiva	UBERON:0001828	90.32	gold quality
thymus	UBERON:0002370	90.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1

miRNA regulators (miRDB)

25 targeting RAE1, 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-4283	100.00	66.42	2097
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-4640-3P	94.58	63.02	263

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 24)

• These data show an association of mrnp41 with MT and, moreover, demonstrate that an intact MT system is necessary for dispersion of mrnp41-containing particles to the cellular periphery (PMID:11831386)
• VSV M protein blocks mRNA export by disrupting Rae1 function, which can be reverted by induction of Rae1 expression. (PMID:15629720)
• A purified Rae1 complex stabilizes microtubules in egg extracts in a RanGTP/importin beta-regulated manner (PMID:15851029)
• point to the Rae1-NuMA interaction as a critical element for normal spindle formation in mitosis (PMID:17172455)
• Retinoic acid downregulates Rae1 leading to APC(Cdh1) activation and neuroblastoma SH-SY5Y differentiation. (PMID:18212744)
• Interaction between Rae1 and cohesin subunit SMC1 is required for proper spindle formation. (PMID:20016259)
• present the crystal structure of human Rae1 in complex with the Gle2-binding sequence (GLEBS) of Nup98 at 1.65 A resolution. Rae1 forms a seven-bladed beta-propeller with several extensive surface loops. (PMID:20498086)
• In a transgenic mouse model of chronic natural killer NKG2D ligand expression, constant exposure to NKG2D ligand RNA export 1 homolog (Rae-1 epsilon) does not functionally impair NK cells or CD8-positive T cells in the context of viral infection. (PMID:20530257)
• RAE1 transgene orchestrates proper chromosome segregation and NUP98-mediated leukemogenesis. (PMID:21467841)
• This study established a novel postmitotic function for rae-1 in neuronal development. (PMID:22357847)
• vesicular stomatitis virus M protein interacted efficiently with Rae1-Nup98 complexes associated with the chromatin fraction of host nuclei, consistent with an effect on host transcription (PMID:23028327)
• mouse cytomegalovirus m152/gp40 interaction with RAE1gamma structural analysis reveals a paradigm for MHC/MHC interaction in immune evasion (PMID:23169621)
• Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1 * Nup98). (PMID:24927547)
• Nuclear export inhibition by ORF10 of human herpesvirus 8 requires an interaction with an RNA export factor, Rae1. (PMID:27832591)
• RAE1 overexpression was associated with considerably poorer disease-free survival and distant metastasis-free survival, especially in patients with oestrogen receptor-positive tumours. (PMID:28181567)
• After PSK administration, INF-g production in CD8(+) T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60. We demonstrated that the expression of NKG2DLs affects tumor immunity and the efficacy of immuno therapy in tumor-bearing mouse model (PMID:28739693)
• show that USP11 is associated with the mitotic spindle, does not regulate SAC inactivation, but controls ubiquitination of RAE1 at the mitotic spindle, hereby functionally modulating its interaction with Nuclear Mitotic Apparatus protein (NuMA). (PMID:29293652)
• RAE1 and NUP98 participate inBMAL1 shuttling and promote the degradation and activity of BMAL1 and CLOCK. (PMID:30683868)
• Lysine acetylation of NKG2D ligand Rae-1 stabilizes the protein and sensitizes tumor cells to NKG2D immune surveillance. (PMID:33279621)
• Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex. (PMID:33360543)
• Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer. (PMID:34008277)
• Super-Enhancer-Driven RAE1 Shows Higher Protein Levels in Tumor Compared to Adjacent Nonmalignant Stroma in High-Grade Serous Ovarian Cancer Patients. (PMID:36810690)
• Insights into the SARS-CoV-2 ORF6 Mechanism of Action. (PMID:37511350)
• SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to inhibit nucleocytoplasmic transport. (PMID:38507240)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rae1	ENSDARG00000007196
mus_musculus	Rae1	ENSMUSG00000027509
rattus_norvegicus	Rae1	ENSRNOG00000021295
drosophila_melanogaster	Rae1	FBGN0034646
drosophila_melanogaster	CG12782	FBGN0034838
caenorhabditis_elegans	rae-1	WBGENE00003803

Paralogs (2): BUB3 (ENSG00000154473), DNAAF10 (ENSG00000243667)

Protein

Protein identifiers

mRNA export factor RAE1 — P78406 (reviewed: P78406)

Alternative names: Rae1 protein homolog, mRNA-associated protein mrnp 41

All UniProt accessions (5): P78406, B0QZ36, B0QZ37, E9PPG9, E9PQ57

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a mRNA export factor involved in nucleocytoplasmic transport. Plays a role in mitotic bipolar spindle formation. May function in attaching cytoplasmic mRNPs to the cytoskeleton both directly or indirectly.

Subunit / interactions. Interacts with NUMA1 (via N-terminal end of the coiled-coil domain); this interaction promotes spindle formation in mitosis. Interacts with NUP98. Interacts with MYCBP2. Interacts with USP11. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 ORF6 protein; the interaction displaces RAE1 from the nuclear envelope and impairs its role in nucleocytoplasmic transport. (Microbial infection) Interacts with SARS coronavirus/SARS-CoV ORF6 protein.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Spindle pole. Nucleus envelope.

Similarity. Belongs to the WD repeat rae1 family.

RefSeq proteins (2): NP_001015885, NP_003601* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400

UniProt features (53 total): strand 31, repeat 7, sequence conflict 5, turn 4, helix 3, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3MMY	X-RAY DIFFRACTION	1.65
7F90	X-RAY DIFFRACTION	2.39
7VPG	X-RAY DIFFRACTION	2.49
7VPH	X-RAY DIFFRACTION	2.8
7F60	X-RAY DIFFRACTION	2.85
4OWR	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78406-F1	93.46	0.90

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 (1): 229

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: 203 (showing top): GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MORF_RAB5A, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, HEIDENBLAD_AMPLICON_8Q24_DN, MORF_PSMC2, GOBP_NUCLEAR_TRANSPORT, REACTOME_HIV_INFECTION, GOBP_REGULATION_OF_SPINDLE_ORGANIZATION, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA

GO Biological Process (6): 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), nucleocytoplasmic transport (GO:0006913), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236)

GO Molecular Function (4): RNA binding (GO:0003723), microtubule binding (GO:0008017), ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (9): fibrillar center (GO:0001650), nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitotic spindle pole (GO:0097431), spindle pole (GO:0000922), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
SUMO E3 ligases SUMOylate target proteins	2
Antimicrobial mechanism of IFN-stimulated genes	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Nuclear Envelope Breakdown	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
chromosome organization	1
RNA transport	1
nuclear export	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
nuclear transport	1
cellular process	1
mitotic spindle organization	1
regulation of spindle organization	1
nucleic acid binding	1
tubulin binding	1
ubiquitin-like protein binding	1
binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
nuclear protein-containing complex	1
nuclear lumen	1
intracellular anatomical structure	1
spindle pole	1
mitotic spindle	1
spindle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAE1	NUP98	P52948	986
RAE1	NXF1	Q9UBU9	964
RAE1	GLE1	Q53GS7	914
RAE1	DDX39B	Q13838	914
RAE1	RBM15B	Q8NDT2	891
RAE1	HNRNPUL1	Q9BUJ2	887
RAE1	ALYREF	Q86V81	871
RAE1	THOC2	Q8NI27	860
RAE1	KLRK1	P26718	812
RAE1	NUP214	P35658	804
RAE1	MAPRE2	Q15555	799
RAE1	NUP42	O15504	792
RAE1	NUP153	P49790	775
RAE1	NXT1	Q9UKK6	770
RAE1	PABPC1	P11940	763

IntAct

157 interactions, top by confidence:

A	B	Type	Score
RAE1	NUP98	psi-mi:“MI:0914”(association)	0.930
NUP98	RAE1	psi-mi:“MI:0915”(physical association)	0.930
NUP98	RAE1	psi-mi:“MI:0407”(direct interaction)	0.930
NUP98	RAE1	psi-mi:“MI:0914”(association)	0.930
RAE1		psi-mi:“MI:0915”(physical association)	0.930
	NUP98	psi-mi:“MI:0914”(association)	0.910
	NUP98	psi-mi:“MI:0915”(physical association)	0.910
NUP98		psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
	NUP98	psi-mi:“MI:0914”(association)	0.840
	NUP98	psi-mi:“MI:0915”(physical association)	0.840
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
RAE1	NUMA1	psi-mi:“MI:0915”(physical association)	0.710

BioGRID (392): NUP98 (Co-crystal Structure), RAE1 (Affinity Capture-MS), RAE1 (Affinity Capture-MS), NUP214 (Affinity Capture-MS), NUP98 (Affinity Capture-MS), AGGF1 (Affinity Capture-MS), PRIM2 (Affinity Capture-MS), POLA1 (Affinity Capture-MS), BUB1B (Affinity Capture-MS), POLA2 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), PRIM1 (Affinity Capture-MS), RAE1 (Affinity Capture-MS), RAE1 (Affinity Capture-MS), AASDHPPT (Co-fractionation)

ESM2 similar proteins: A0A1W5T363, A5DGL8, A5DVY3, A5GFN6, A8QBF3, A8WVX8, B0XFT7, B3N4C7, B4GSH1, B4I195, B4JB43, B4Q354, G0SEA3, O02195, O14301, O42937, O75083, O88342, O93277, P27133, P40066, P41838, P78406, Q16K15, Q26613, Q29L19, Q2KJH4, Q38942, Q3SWS8, Q4R6D2, Q54DM1, Q5AI86, Q5E9A4, Q5FVA9, Q5RF99, Q5RKI0, Q6CI08, Q6DIF4, Q6PAX7, Q759L2

Diamond homologs: A0A1W5T363, A5GFN6, A8IR43, G0SEA3, O42860, O43684, O60097, P40066, P41838, P78406, Q1JQB2, Q38942, Q3SWS8, Q4R6D2, Q54DM1, Q5E9A4, Q5FVA9, Q5RB58, Q5RF99, Q7ZWF0, Q8C570, Q8VYZ5, Q93454, Q9C1X1, Q9C701, Q9LJN8, Q9W2E7, Q9WVA3, Q9XWH0, Q9YGY3, S8ASK6, O43071, O93277, Q54MP8, Q5ZJW8, Q6GPU3, Q9FE91, O60907, Q4R8H1, Q95RJ9

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
RAE1	“up-regulates activity”	NUP98	binding
Interferon-type-I	“up-regulates quantity by expression”	RAE1	“transcriptional regulation”
RAE1	up-regulates	mRNA_nuclear_export
6	“down-regulates activity”	RAE1	binding
RAE1	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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	34.2×	7e-12
NEP/NS2 Interacts with the Cellular Export Machinery	10	33.9×	6e-11
Nuclear import of Rev protein	10	32.9×	6e-11
Transport of Ribonucleoproteins into the Host Nucleus	9	31.5×	9e-10
IPs transport between nucleus and cytosol	8	29.9×	9e-09
IP3 and IP4 transport between cytosol and nucleus	8	29.9×	9e-09
IP6 and IP7 transport between cytosol and nucleus	8	29.9×	9e-09
Vpr-mediated nuclear import of PICs	9	29.6×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	6	43.2×	1e-06
nucleocytoplasmic transport	9	27.1×	4e-08
protein export from nucleus	5	19.6×	1e-03
establishment of mitotic spindle orientation	5	18.5×	1e-03
mRNA export from nucleus	7	15.9×	7e-05
protein import into nucleus	12	13.3×	6e-08
mRNA transport	6	12.2×	2e-03

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	22
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2464 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:57356450:G:C	R67P	1.000
20:57356455:T:A	W69R	1.000
20:57356455:T:C	W69R	1.000
20:57365404:T:A	W113R	1.000
20:57365404:T:C	W113R	1.000
20:57368802:T:C	L211P	1.000
20:57373520:G:C	G230R	1.000
20:57373521:G:A	G230D	1.000
20:57373527:C:A	A232D	1.000
20:57373532:G:A	G234R	1.000
20:57373532:G:C	G234R	1.000
20:57373533:G:A	G234E	1.000
20:57373535:A:C	S235R	1.000
20:57373537:T:A	S235R	1.000
20:57373537:T:G	S235R	1.000
20:57373541:G:A	E237K	1.000
20:57373544:G:A	G238R	1.000
20:57373544:G:C	G238R	1.000
20:57373544:G:T	G238W	1.000
20:57373545:G:A	G238E	1.000
20:57373545:G:T	G238V	1.000
20:57373547:A:G	R239G	1.000
20:57373548:G:C	R239T	1.000
20:57373548:G:T	R239I	1.000
20:57373549:A:C	R239S	1.000
20:57373549:A:T	R239S	1.000
20:57373551:T:A	V240D	1.000
20:57373553:G:C	A241P	1.000
20:57373554:C:A	A241D	1.000
20:57373557:T:A	I242N	1.000

dbSNP variants (sampled 300 via entrez): RS1000066145 (20:57377742 G>T), RS1000151698 (20:57377516 C>T), RS1000208804 (20:57369328 T>C), RS1000286074 (20:57356907 A>T), RS1000355948 (20:57361804 G>A), RS1000406440 (20:57374257 C>A,G,T), RS1000470608 (20:57379453 G>A), RS1000547040 (20:57368404 A>G), RS1000601632 (20:57369511 G>A), RS1000714107 (20:57373061 G>A,T), RS1000755497 (20:57378577 G>A), RS1000820725 (20:57358199 G>A), RS1000899608 (20:57378251 C>T), RS1000915623 (20:57358056 T>C), RS1001103836 (20:57352095 T>A)

Disease associations

OMIM: gene MIM:603343 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066294 (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
8.15	Kd	7.018	nM	CHEMBL5653589
8.15	ED50	7.018	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	2149187: Binding affinity to human RAE1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
deoxynivalenol	increases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
nivalenol	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Coumestrol	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Naled	affects expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Rotenone	increases expression	1
Smoke	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
CHEMBL5652229	Binding	Binding affinity to human RAE1 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.