RANBP2

Summary

RANBP2 (RAN binding protein 2, HGNC:9848) is a protein-coding gene on chromosome 2q13, encoding E3 SUMO-protein ligase RanBP2 (P49792). E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. It is a selective cancer dependency (DepMap: 51.2% of cell lines).

RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q.

Source: NCBI Gene 5903 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial acute necrotizing encephalopathy (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 1,736 total — 7 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 51.2% of screened cell lines
• MANE Select transcript: NM_006267

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9848
Approved symbol	RANBP2
Name	RAN binding protein 2
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	NUP358, ADANE
Ensembl gene	ENSG00000153201
Ensembl biotype	protein_coding
OMIM	601181
Entrez	5903

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 12 retained_intron, 9 protein_coding, 2 nonsense_mediated_decay

ENST00000283195, ENST00000425282, ENST00000495506, ENST00000495924, ENST00000697737, ENST00000697738, ENST00000697739, ENST00000697740, ENST00000697741, ENST00000697742, ENST00000697743, ENST00000697744, ENST00000697745, ENST00000697746, ENST00000697747, ENST00000697748, ENST00000697749, ENST00000697750, ENST00000697751, ENST00000917983, ENST00000917984, ENST00000960085, ENST00000960086

RefSeq mRNA: 4 — MANE Select: NM_006267 NM_001415871, NM_001415872, NM_001415873, NM_006267

CCDS: CCDS2079

Canonical transcript exons

ENST00000283195 — 29 exons

Exon	Start	End
ENSE00001009418	108771701	108771871
ENSE00001009419	108775732	108775936
ENSE00001009428	108777130	108777231
ENSE00001009429	108772489	108772581
ENSE00001147257	108782528	108782862
ENSE00001147357	108763237	108768388
ENSE00001291545	108772868	108773046
ENSE00001316371	108783596	108785809
ENSE00001377207	108781269	108781429
ENSE00001383394	108782128	108782401
ENSE00001427934	108719482	108719678
ENSE00001785652	108740489	108740681
ENSE00002437359	108751528	108751703
ENSE00002437505	108762101	108762195
ENSE00002439890	108730774	108730885
ENSE00002459851	108753825	108753971
ENSE00002472646	108754905	108755084
ENSE00002476126	108735532	108735762
ENSE00002476777	108748920	108749129
ENSE00002479403	108755176	108755259
ENSE00002497068	108736104	108736249
ENSE00002509667	108751264	108751445
ENSE00002510422	108746711	108746798
ENSE00002513403	108751871	108751994
ENSE00002522596	108758413	108758548
ENSE00002524114	108752998	108753159
ENSE00002533119	108753426	108753563
ENSE00003241565	108729132	108729199
ENSE00003641991	108731322	108731474

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.3895 / max 583.0253, expressed in 1809 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21910	38.7634	1808
21909	1.2309	754
21911	1.1889	310
21912	0.1079	39
21916	0.0792	10
21917	0.0192	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.70	gold quality
sperm	CL:0000019	97.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.37	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.17	gold quality
blood vessel layer	UBERON:0004797	96.95	gold quality
epithelium of nasopharynx	UBERON:0001951	96.75	gold quality
tibia	UBERON:0000979	96.72	gold quality
visceral pleura	UBERON:0002401	96.60	gold quality
superficial temporal artery	UBERON:0001614	96.59	gold quality
seminal vesicle	UBERON:0000998	96.51	gold quality
germinal epithelium of ovary	UBERON:0001304	96.44	gold quality
parietal pleura	UBERON:0002400	96.38	gold quality
pleura	UBERON:0000977	96.36	gold quality
male germ cell	CL:0000015	96.33	gold quality
oral cavity	UBERON:0000167	96.23	gold quality
choroid plexus epithelium	UBERON:0003911	96.03	gold quality
biceps brachii	UBERON:0001507	95.90	gold quality
superior surface of tongue	UBERON:0007371	95.85	gold quality
penis	UBERON:0000989	95.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.72	gold quality
corpus epididymis	UBERON:0004359	95.58	gold quality
skin of hip	UBERON:0001554	95.51	gold quality
adrenal tissue	UBERON:0018303	95.46	gold quality
calcaneal tendon	UBERON:0003701	95.45	gold quality
jejunum	UBERON:0002115	95.43	gold quality
gluteal muscle	UBERON:0002000	95.34	gold quality
upper leg skin	UBERON:0004262	95.30	gold quality
gingival epithelium	UBERON:0001949	95.24	gold quality
urethra	UBERON:0000057	95.23	gold quality
cardia of stomach	UBERON:0001162	95.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	23.03
E-ANND-3	yes	10.13
E-MTAB-7008	no	192.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYOD1

miRNA regulators (miRDB)

103 targeting RANBP2, 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-4668-3P	100.00	68.74	2635
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 51.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• reports identification of a binding domain in RanBP2, the zinc-finger rich domain, toward CRM1/exportin-1 (PMID:10601307)
• reports identification of a novel domain in RanBP2 located between RBD2 and RBD3 with specific binding activity against the conventional heavy chain kinesins, KIF5B and KIF5C (PMID:11553612)
• Here, we define a Pro-Glu-Asp-Ser-Thr-rich element containing 129 amino acid residues, designated IR1+2, on the human nucleoporin RanBP2/Nup358, which binds directly to Ubc9 with high affinity both in vitro and in vivo (PMID:11709548)
• The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase (PMID:12032081)
• identification of RanBP2-mediated transport pathways with restricted neuronal and subcellular localization (PMID:12191015)
• reports the novel subcellular localizations of RanBP2 in retinal neurons of human and bovine (PMID:12191015)
• RanBP2 sumoylates MDM2 during nuclear translocation in human cells (PMID:12393906)
• Without Nup358, chromosome congression and segregation are severely perturbed. Meanwhile, the assembly of other kinetochore components is strongly inhibited. (PMID:12963708)
• RanGAP1 remains associated with RanBP2/Nup358 and the SUMO E2-conjugating enzyme Ubc9 in mitosis. (PMID:15037602)
• Ubc9- small ubiquitin-like modifier (SUMO-1) thioester could be recruited to RanBP2 via SUMO-1 in the absence of strong binding between Ubc9 and RanBP2 (PMID:15608651)
• Nup358/RanBP2 acts as an E3 by binding both SUMO and Ubc9 to position the SUMO-E2-thioester in an optimal orientation to enhance conjugation (PMID:15931224)
• the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways (PMID:16332688)
• The Trp2 allele is an age-dependent risk factor for the severity of disc degeneration in younger patients with symptomatic herniated nucleus pulposus of the lumbar spine. (PMID:16586133)
• Our data imply that SUMO E3 proteins like RanBP2 facilitate spatio-temporal SUMOylation for certain nuclear structure and function. (PMID:16688858)
• ent-15-oxokaurenoic acid inhibits mitotic chromosome movement and binds the kinetochore protein ran-binding protein 2 (PMID:17168522)
• binding of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function (PMID:17887960)
• Biopsy samples from 288 patients suffering from LDD with and without relapse were analyzed by PCR restriction fragment analysis and direct sequencing. The mutated Trp2 allele was not detected in the patients’ samples of the present study. (PMID:18080148)
• These data suggest a dual function of the Nup358-RanGAP1 complex as a coordinator of importin beta recycling and reformation of novel import complexes. (PMID:18305100)
• Silencing of the RANBP2 E3 ligase reverts HDAC 4 repression by blocking its own sumoylation (PMID:18691615)
• Data describe a mitotic SUMO2/3 conjugation-deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway. (PMID:18946085)
• missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE. (PMID:19118815)
• Upregulated in at least 50% of multiple myeloma cases tested. (PMID:19171422)
• The nuclear pore component Nup358 promotes transportin-dependent nuclear import. (PMID:19299463)
• RANBP2 is the first native and positive allosteric activator known to jump-start and boost directly the activity of KIF5B. (PMID:19305391)
• The middle region of APC is sufficient to recruit Nup358 to the plus ends of microtubules. (PMID:19654215)
• ANE may, in some instances, represent a familial disorder or may be the result of an inherited predisposition due to a mutation in the RANBP2 gene. It also broadens the phenotype of neurological problems in individuals that harbour a RANBP2 mutation. (PMID:19807769)
• Both the patient and her mother, who had also had postviral polyneuritis in the past, harbour a mutation in Ran-binding protein 2 (RANBP2); this occurred de novo in the mother and confers genetic susceptibility to ANE. (PMID:19811512)
• Oxidative stress up-regulated the binding of Crm1 to Ran and affected multiple repeat-containing nucleoporins by changing their localization, phosphorylation, O-glycosylation, or interaction with other transport components. (PMID:19828735)
• Untreated recurrent acute necrotising encephalopathy associated with RANBP2 missense mutation, and normal outcome in a Caucasian boy. (PMID:20473521)
• RanBP2 is a host factor that is involved in the nuclear import of HIV-1 PIC (DNA), but is not critical to the nuclear export of the viral mRNAs or nucleo-cytoplasmic shuttling of Rev (PMID:21179483)
• Data establish a subset of RANBP2-type zinc fingers as a new family of ssRNA-binding motifs. (PMID:21256132)
• This study measures for the first time the activation entropy and enthalpy of ubiquitin-like modifications and finds that the E3 ligase, RanBP2, confers a large entropic effect to lower the activation energy, thereby accelerating the reactions. (PMID:21568279)
• Data show that Epac1 directly interacts with the zinc fingers of RanBP2, tethering Epac1 to the nuclear pore complex, revealing a novel mechanism of Epac1 regulation and an unexpected link between the NPC and cAMP signaling. (PMID:21670213)
• A critical function of RanBP2 is to capture recycling RanGTP-importin-beta complexes at cytoplasmic fibrils to allow for adequate classical nuclear localization signal-mediated cargo import. (PMID:21859863)
• Nup358 functions as a cargo- and receptor-specific assembly platform, increasing the efficiency of nuclear import of proteins through various mechanisms. (PMID:21995724)
• Determinants of small ubiquitin-like modifier 1 (SUMO1) protein specificity, E3 ligase, and SUMO-RanGAP1 binding activities of nucleoporin RanBP2. (PMID:22194619)
• Knockdown of RANBP2 specifically affected the late step of nuclear entry, inducing cytoplasmic granules enriched with phosphorylated components. This suggests a novel regulatory mechanism for nuclear speckle formation involving RANBP2 and phosphorylation. (PMID:22262462)
• The structure reveals that the C-terminal domain adopts a cyclophilin-like fold with a non-canonical active-site configuration. (PMID:23353830)
• The translation of a subset of mRNAs encoding secretory proteins is potentiated by RanBP2. (PMID:23630457)
• These findings reveal novel roles of Ranbp2 in the modulation of intrinsic and extrinsic cell death mechanisms and pathways (PMID:23818861)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ranbp1	ENSDARG00000014817
mus_musculus	Ranbp2	ENSMUSG00000003226
rattus_norvegicus	Ranbp2	ENSRNOG00000000796

Paralogs (10): RGPD5 (ENSG00000015568), RANBP3 (ENSG00000031823), RANBP1 (ENSG00000099901), RGPD3 (ENSG00000153165), RANBP3L (ENSG00000164188), RGPD8 (ENSG00000169629), RGPD6 (ENSG00000183054), RGPD2 (ENSG00000185304), RGPD1 (ENSG00000187627), RGPD4 (ENSG00000196862)

Protein

Protein identifiers

E3 SUMO-protein ligase RanBP2 — P49792 (reviewed: P49792)

Alternative names: 358 kDa nucleoporin, Nuclear pore complex protein Nup358, Nucleoporin Nup358, Ran-binding protein 2, p270

All UniProt accessions (7): P49792, A0A8V8TL79, A0A8V8TLA0, A0A8V8TLN4, A0A8V8TMN6, A0A8V8TMX6, F8WBP7

UniProt curated annotations — full annotation on UniProt →

Function. E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Binds single-stranded RNA (in vitro). May bind DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1. Inhibits EIF4E-dependent mRNA export. Sumoylates PML at ‘Lys-490’ which is essential for the proper assembly of PML-NB. Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity.

Subunit / interactions. Part of the nuclear pore complex. Forms a complex with NXT1, NXF1 and RANGAP1. Forms a tight complex with RANBP1 and UBE2I. Interacts with SUMO1 but not SUMO2. Interacts with PRKN. Interacts with sumoylated RANGAP1. Interacts with CDCA8. Interacts with PML (isoform PML-4). Interacts with BICD2. Interacts with MCM3AP isoform GANP. Interacts with COX11. Interacts with synaptic plasticity regulator PANTS. (Microbial infection) Interacts with HIV-1 Vpu protein; this interaction allows Vpu to down-regulate BLM sumoylation.

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

Post-translational modifications. Polyubiquitinated by PRKN, which leads to proteasomal degradation. 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. Encephalopathy, acute, infection-induced, 3 (IIAE3) [MIM:608033] A rapidly progressive encephalopathy manifesting in susceptible individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. The disease is caused by variants affecting the gene represented in this entry. Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required. A chromosomal aberration involving RANBP2 is a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(2;8)(q12;p11) with FGFR1. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia.

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. The PPIase cyclophilin-type domain has high structural similarity with PPIA, but has extremely low and barely detectable proline isomerase activity (in vitro). Only about half of the residues that surround the PPIA active site cleft are conserved.

Pathway. Protein modification; protein sumoylation.

Similarity. Belongs to the RanBP2 E3 ligase family.

RefSeq proteins (4): NP_001402800, NP_001402801, NP_001402802, NP_006258* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000156	Ran_bind_dom	Domain
IPR001876	Znf_RanBP2	Domain
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR022011	IR1-M	Domain
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR045255	RanBP1-like	Family

Pfam: PF00160, PF00638, PF00641, PF12185

UniProt features (283 total): modified residue 53, strand 43, turn 34, repeat 31, helix 22, cross-link 19, region of interest 18, mutagenesis site 17, compositionally biased region 12, sequence variant 11, sequence conflict 8, zinc finger region 8, domain 5, chain 1, site 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7MNK	X-RAY DIFFRACTION	1.1
4GA0	X-RAY DIFFRACTION	1.15
4I9Y	X-RAY DIFFRACTION	1.75
7MNR	X-RAY DIFFRACTION	1.8
7MNV	X-RAY DIFFRACTION	1.8
4LQW	X-RAY DIFFRACTION	1.95
7MNU	X-RAY DIFFRACTION	2
7MNP	X-RAY DIFFRACTION	2.05
7MNQ	X-RAY DIFFRACTION	2.05
7MNS	X-RAY DIFFRACTION	2.1
3UIP	X-RAY DIFFRACTION	2.29
7MNZ	X-RAY DIFFRACTION	2.35
7MNW	X-RAY DIFFRACTION	2.4
7MNX	X-RAY DIFFRACTION	2.4
5CLL	X-RAY DIFFRACTION	2.45
7MNT	X-RAY DIFFRACTION	2.45
4L6E	X-RAY DIFFRACTION	2.5
3UIN	X-RAY DIFFRACTION	2.6
3UIO	X-RAY DIFFRACTION	2.6
7MNY	X-RAY DIFFRACTION	2.7
9B62	ELECTRON MICROSCOPY	2.9
1RRP	X-RAY DIFFRACTION	2.96
1Z5S	X-RAY DIFFRACTION	3.01
5CLQ	X-RAY DIFFRACTION	3.2
7MNJ	X-RAY DIFFRACTION	3.8
7MNL	X-RAY DIFFRACTION	3.95
7MNM	X-RAY DIFFRACTION	4.7
7MNN	X-RAY DIFFRACTION	6.7
7MNO	X-RAY DIFFRACTION	6.73
7R5K	ELECTRON MICROSCOPY	12

Predicted structure (AlphaFold)

No AlphaFold model available for P49792 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Antibody-complex structures (SAbDab): 4 — 7MNL, 7MNM, 7MNN, 7MNO

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 932–933 (breakpoint for translocation to form ranbp2-fgfr1 protein)

Post-translational modifications (72): 1520, 1573, 1833, 1835, 1869, 1871, 1977, 2005, 2008, 2153, 2246, 2251, 2270, 2280, 2290, 2293, 2297, 2462, 2493, 2510 …

Mutagenesis-validated functional residues (17):

Position	Phenotype
2632	abolishes interaction with sumoylated rangap1.
2634	abolishes interaction with sumoylated rangap1.
2635	abolishes interaction with sumoylated rangap1.
2640	no effect on sumo e3 ligase activity.
2645	no effect on sumo e3 ligase activity.
2651	abolishes binding to ube2i and sumo e3 ligase activity.
2652	no effect on sumo e3 ligase activity.
2653	abolishes binding to ube2i and sumo e3 ligase activity.
2654	impairs sumo e3 ligase activity.
2655	no effect on sumo e3 ligase activity.
2656	impairs sumo e3 ligase activity.
2657	abolishes binding to ube2i and sumo e3 ligase activity.
2658	abolishes binding to ube2i and sumo e3 ligase activity.
2659	impairs sumo e3 ligase activity.
2676	impairs sumo e3 ligase activity.
2677	impairs sumo e3 ligase activity.
2689	impairs sumo e3 ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-180746	Nuclear import of Rev protein
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-1855170	IPs transport between nucleus and cytosol
R-HSA-1855196	IP3 and IP4 transport between cytosol and nucleus
R-HSA-1855229	IP6 and IP7 transport between cytosol and nucleus
R-HSA-191859	snRNP Assembly
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-5663220	RHO GTPases Activate Formins

MSigDB gene sets: 369 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GGGACCA_MIR133A_MIR133B, PID_HDAC_CLASSI_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AAGCAAT_MIR137, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, ACTACCT_MIR196A_MIR196B, GOBP_RESPONSE_TO_AMINE, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TTTGTAG_MIR520D, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GTTAAAG_MIR302B

GO Biological Process (18): negative regulation of transcription by RNA polymerase II (GO:0000122), intracellular glucose homeostasis (GO:0001678), response to amphetamine (GO:0001975), regulation of gluconeogenesis (GO:0006111), protein folding (GO:0006457), NLS-bearing protein import into nucleus (GO:0006607), nucleocytoplasmic transport (GO:0006913), protein sumoylation (GO:0016925), mRNA transport (GO:0051028), nuclear export (GO:0051168), centrosome localization (GO:0051642), protein peptidyl-prolyl isomerization (GO:0000413), toll-like receptor signaling pathway (GO:0002224), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), protein transport (GO:0015031), negative regulation of innate immune response (GO:0045824), negative regulation of RNA export from nucleus (GO:0046832), intracellular transport (GO:0046907)

GO Molecular Function (13): RNA binding (GO:0003723), zinc ion binding (GO:0008270), kinase activator activity (GO:0019209), SUMO transferase activity (GO:0019789), protein-macromolecule adaptor activity (GO:0030674), small GTPase binding (GO:0031267), protein-containing complex binding (GO:0044877), SUMO ligase activity (GO:0061665), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), GTPase activator activity (GO:0005096), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (14): nucleus (GO:0005634), nuclear envelope (GO:0005635), annulate lamellae (GO:0005642), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nuclear membrane (GO:0031965), nuclear inclusion body (GO:0042405), nuclear pore cytoplasmic filaments (GO:0044614), nuclear pore nuclear basket (GO:0044615), SUMO ligase complex (GO:0106068), cytoplasmic periphery of the nuclear pore complex (GO:1990723)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
Antimicrobial mechanism of IFN-stimulated genes	1
Amplification of signal from the kinetochores	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Mitotic Anaphase	1
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nucleus	3
nuclear protein-containing complex	3
pattern recognition receptor signaling pathway	2
transport	2
intracellular anatomical structure	2
enzyme activator activity	2
binding	2
nuclear envelope	2
nuclear pore	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
glucose homeostasis	1
intracellular chemical homeostasis	1
response to amine	1
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
cellular process	1
protein maturation	1
protein import into nucleus	1
nuclear transport	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
RNA transport	1
nucleocytoplasmic transport	1
intercellular transport	1
microtubule organizing center localization	1
peptidyl-proline modification	1
positive regulation of cytokine production	1
intracellular receptor signaling pathway	1
intracellular protein localization	1
establishment of protein localization	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1

Protein interactions and networks

STRING

6564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RANBP2	RANGAP1	P46060	999
RANBP2	UBE2I	P50550	998
RANBP2	NUP214	P35658	997
RANBP2	SUMO1	P55856	997
RANBP2	BICD2	Q8TD16	993
RANBP2	NUP88	Q99567	993
RANBP2	KIF5C	O60282	990
RANBP2	NUP98	P52948	975
RANBP2	KIF5B	P33176	969
RANBP2	XPO1	O14980	965
RANBP2	RAN	P17080	946
RANBP2	NUP62	P37198	939
RANBP2	NUP133	Q8WUM0	922
RANBP2	NUP155	O75694	919
RANBP2	NUP35	Q8NFH5	916
RANBP2	AHCTF1	Q8WYP5	916

IntAct

245 interactions, top by confidence:

A	B	Type	Score
RAN	RANBP2	psi-mi:“MI:0407”(direct interaction)	0.860
RAN	RANBP2	psi-mi:“MI:0915”(physical association)	0.860
RANBP2	RANGAP1	psi-mi:“MI:0407”(direct interaction)	0.710
RANGAP1	RANBP2	psi-mi:“MI:0407”(direct interaction)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
B2M	NEMP1	psi-mi:“MI:0914”(association)	0.640
RAN	RGPD8	psi-mi:“MI:0914”(association)	0.640
NEMP1	RANGAP1	psi-mi:“MI:0914”(association)	0.640
Bicd2	RANBP2	psi-mi:“MI:0407”(direct interaction)	0.630
Bicd2	RANBP2	psi-mi:“MI:0915”(physical association)	0.630
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
RANBP2	KPNA2	psi-mi:“MI:0915”(physical association)	0.550
RANBP2	C7orf25	psi-mi:“MI:0407”(direct interaction)	0.540
C7orf25	RANBP2	psi-mi:“MI:0915”(physical association)	0.540
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
B2M	KPNA3	psi-mi:“MI:0914”(association)	0.530

BioGRID (539): RANGAP1 (Reconstituted Complex), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANBP2 (Reconstituted Complex), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS), RANBP2 (Affinity Capture-Western), CDCA8 (Biochemical Activity), SUMO1 (Reconstituted Complex), RANBP2 (Biochemical Activity), RANBP2 (Affinity Capture-Western)

ESM2 similar proteins: A0A0B4K7J2, A1ZAK1, A6NKT7, F4J8D3, G5ED39, H2QII6, O01510, O14715, O48767, P0DJD0, P0DJD1, P12798, P33144, P40358, P42286, P49792, Q00416, Q0IEK6, Q18508, Q18892, Q20937, Q291E4, Q2U639, Q4WVM7, Q5B8K7, Q61CW2, Q61WP7, Q6C9G0, Q6CXL5, Q6FUS3, Q6FVG5, Q70PP2, Q751J3, Q754V0, Q759B7, Q759Y1, Q75B70, Q75CM2, Q7TSH2, Q7Z3J3

Diamond homologs: A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, D4AY02, F5H284, H2QII6, O00060, O49886, O93826, P0C1H7, P0C1H8, P0C1I2, P0C1I7, P0C1I8, P0C1I9, P0CP78, P0CP79, P0DN26, P0DN37, P10111, P10255, P14088, P14832, P14851, P17742, P18253, P21568, P21569, P22011, P24367, P24525, P25007, P25719, P29117, P30404, P30405, P34790, P34791

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
RANBP2	“down-regulates quantity”	CDKN1B	relocalization
PRKN	“down-regulates quantity by destabilization”	RANBP2	ubiquitination
RANBP2	“up-regulates quantity”	BICD2	relocalization
RANBP2	“up-regulates activity”	TNPO1	binding
CDK1	“up-regulates activity”	RANBP2	phosphorylation
RANBP2	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 208 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	13	31.7×	4e-14
Postmitotic nuclear pore complex (NPC) reformation	10	31.4×	5e-11
Nuclear import of Rev protein	11	28.4×	2e-11
NEP/NS2 Interacts with the Cellular Export Machinery	10	26.6×	3e-10
NS1 Mediated Effects on Host Pathways	12	26.4×	5e-12
Transport of Ribonucleoproteins into the Host Nucleus	9	24.7×	5e-09
IPs transport between nucleus and cytosol	8	23.4×	6e-08
IP3 and IP4 transport between cytosol and nucleus	8	23.4×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	9	42.7×	1e-10
RNA export from nucleus	7	38.8×	1e-07
nucleocytoplasmic transport	9	20.9×	1e-07
protein export from nucleus	6	18.1×	2e-04
mRNA transport	10	15.6×	2e-07
protein import into nucleus	17	14.5×	3e-12
mRNA export from nucleus	6	10.5×	3e-03
regulation of alternative mRNA splicing, via spliceosome	6	8.7×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — CCRCC, HCC, LUSC, NBL, PGNG.

Clinical variants and AI predictions

ClinVar

1736 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	6
Uncertain significance	1204
Likely benign	307
Benign	65

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1322816	NM_022336.4(EDAR):c.1004del (p.Asn335fs)	Pathogenic
1401027	NM_022336.4(EDAR):c.1151_1154dup (p.Asp386fs)	Pathogenic
163325	NM_022336.3(EDAR):c.(?998)(1347_?)del	Pathogenic
2203127	NM_022336.4(EDAR):c.73C>T (p.Arg25Ter)	Pathogenic
3757074	NM_022336.4(EDAR):c.1164del (p.Ile388fs)	Pathogenic
5854	NM_022336.4(EDAR):c.51+1G>A	Pathogenic
5857	NM_022336.4(EDAR):c.1060G>T (p.Glu354Ter)	Pathogenic
3065283	NM_006267.5(RANBP2):c.5822_5823insTG (p.Ser1942fs)	Likely pathogenic
3065984	NM_006267.5(RANBP2):c.2070G>T (p.Lys690Asn)	Likely pathogenic
393529	NM_006267.5(RANBP2):c.5249C>G (p.Pro1750Arg)	Likely pathogenic
429792	NM_006267.5(RANBP2):c.3125G>A (p.Gly1042Asp)	Likely pathogenic
4539015	NM_022336.4(EDAR):c.1084dup (p.Ser362fs)	Likely pathogenic
847026	NM_022336.4(EDAR):c.973C>T (p.Arg325Trp)	Likely pathogenic

SpliceAI

3829 predictions. Top by Δscore:

Variant	Effect	Δscore
2:108719675:ACAGG:A	donor_loss	1.0000
2:108719676:CAGGT:C	donor_loss	1.0000
2:108719677:AGGT:A	donor_loss	1.0000
2:108719679:G:GA	donor_loss	1.0000
2:108719680:T:A	donor_loss	1.0000
2:108729126:TTTTA:T	acceptor_loss	1.0000
2:108729127:TTTA:T	acceptor_loss	1.0000
2:108729128:TTA:T	acceptor_loss	1.0000
2:108729129:TA:T	acceptor_loss	1.0000
2:108729130:A:AC	acceptor_loss	1.0000
2:108729130:A:AG	acceptor_gain	1.0000
2:108729131:G:GA	acceptor_gain	1.0000
2:108729131:G:GT	acceptor_loss	1.0000
2:108729131:GA:G	acceptor_gain	1.0000
2:108729131:GAA:G	acceptor_gain	1.0000
2:108729131:GAAGT:G	acceptor_gain	1.0000
2:108729196:AAAAG:A	donor_loss	1.0000
2:108729197:AAA:A	donor_gain	1.0000
2:108729197:AAAGT:A	donor_loss	1.0000
2:108729198:AA:A	donor_gain	1.0000
2:108729199:AG:A	donor_loss	1.0000
2:108729200:G:GG	donor_gain	1.0000
2:108729200:GTA:G	donor_loss	1.0000
2:108729201:TA:T	donor_loss	1.0000
2:108729202:AAG:A	donor_loss	1.0000
2:108729203:AGT:A	donor_loss	1.0000
2:108730766:A:G	acceptor_gain	1.0000
2:108730773:GATAC:G	acceptor_gain	1.0000
2:108730884:GG:G	donor_gain	1.0000
2:108730885:GG:G	donor_gain	1.0000

AlphaMissense

21328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:108764147:G:C	R1203P	1.000
2:108764170:T:A	W1211R	1.000
2:108764170:T:C	W1211R	1.000
2:108764172:G:C	W1211C	1.000
2:108764172:G:T	W1211C	1.000
2:108764180:G:C	R1214P	1.000
2:108764182:G:A	G1215R	1.000
2:108764182:G:C	G1215R	1.000
2:108764183:G:A	G1215E	1.000
2:108764246:G:C	R1236P	1.000
2:108764335:T:A	W1266R	1.000
2:108764335:T:C	W1266R	1.000
2:108766664:T:A	L2042Q	1.000
2:108766664:T:C	L2042P	1.000
2:108766693:T:A	W2052R	1.000
2:108766693:T:C	W2052R	1.000
2:108766695:G:C	W2052C	1.000
2:108766695:G:T	W2052C	1.000
2:108766704:G:C	R2055S	1.000
2:108766704:G:T	R2055S	1.000
2:108766705:G:C	G2056R	1.000
2:108766706:G:A	G2056D	1.000
2:108766711:G:A	G2058R	1.000
2:108766711:G:C	G2058R	1.000
2:108766711:G:T	G2058W	1.000
2:108766712:G:A	G2058E	1.000
2:108766712:G:T	G2058V	1.000
2:108766727:T:C	L2063P	1.000
2:108766754:G:C	R2072T	1.000
2:108766755:A:C	R2072S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001447 (2:109494755 A>T), RS1000010484 (2:109619019 C>T), RS1000010939 (2:108965575 G>A), RS1000011024 (2:109185342 G>T), RS1000012768 (2:109104782 C>T), RS1000013775 (2:109088060 C>T), RS1000014075 (2:109313734 T>C), RS1000014844 (2:108840757 T>C,G), RS1000021593 (2:109458965 G>A), RS1000023920 (2:109053261 C>A,G,T), RS1000026494 (2:108931525 A>C), RS1000026654 (2:108756561 A>T), RS1000028371 (2:108833257 A>T), RS1000029237 (2:109707580 C>T), RS1000029304 (2:108815569 G>A)

Disease associations

OMIM: gene MIM:601181 | disease phenotypes: MIM:608033, MIM:129490, MIM:224900, MIM:168300, MIM:170500, MIM:613345, MIM:614198, MIM:608390, MIM:609423, MIM:305100, MIM:603553

GenCC curated gene-disease

Disease	Classification	Inheritance
familial acute necrotizing encephalopathy	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Leigh syndrome	Limited	AD
familial acute necrotizing encephalopathy	Moderate	AD

Mondo (16): familial acute necrotizing encephalopathy (MONDO:0011953), ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (MONDO:0007509), autosomal recessive hypohidrotic ectodermal dysplasia (MONDO:0016619), ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (MONDO:0009147), hypohidrotic ectodermal dysplasia (MONDO:0016535), autosomal dominant hypohidrotic ectodermal dysplasia (MONDO:0015884), paramyotonia congenita of Von Eulenburg (MONDO:0008195), hyperkalemic periodic paralysis (MONDO:0008224), hypokalemic periodic paralysis, type 2 (MONDO:0013234), congenital myasthenic syndrome 16 (MONDO:0013620), potassium-aggravated myotonia (MONDO:0018959), susceptibility to HIV infection (MONDO:0004951), intellectual disability (MONDO:0001071), hereditary ataxia (MONDO:0100309), ectodermal dysplasia syndrome (MONDO:0019287)

Orphanet (16): Familial acute necrotizing encephalopathy (Orphanet:88619), Autosomal dominant hypohidrotic ectodermal dysplasia (Orphanet:1810), Hypohidrotic ectodermal dysplasia (Orphanet:238468), Autosomal recessive hypohidrotic ectodermal dysplasia (Orphanet:248), Congenital myasthenic syndrome (Orphanet:590), Potassium-aggravated myotonia (Orphanet:612), Hypokalemic periodic paralysis (Orphanet:681), Hyperkalemic periodic paralysis (Orphanet:682), Paramyotonia congenita of Von Eulenburg (Orphanet:684), Myotonia fluctuans (Orphanet:99734), Myotonia permanens (Orphanet:99735), Acetazolamide-responsive myotonia (Orphanet:99736), Hereditary ataxia (Orphanet:183518), Ectodermal dysplasia syndrome (Orphanet:79373), Familial hemophagocytic lymphohistiocytosis (Orphanet:540)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001259	Coma
HP:0001260	Dysarthria
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001298	Encephalopathy
HP:0001945	Fever
HP:0002013	Vomiting
HP:0002063	Rigidity
HP:0002090	Pneumonia
HP:0002171	Gliosis
HP:0002181	Cerebral edema
HP:0002363	Abnormal brainstem morphology
HP:0002376	Developmental regression
HP:0002445	Tetraplegia
HP:0002510	Spastic tetraplegia
HP:0002715	Abnormality of the immune system
HP:0002793	Abnormal pattern of respiration
HP:0002922	Increased CSF protein concentration
HP:0003324	Generalized muscle weakness
HP:0003593	Infantile onset
HP:0003829	Typified by incomplete penetrance
HP:0006846	Acute encephalopathy
HP:0010663	Abnormal thalamus morphology
HP:0011887	Choroid hemorrhage
HP:0012747	Abnormal brainstem MRI signal intensity
HP:0025404	Abnormal visual fixation

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003474_7	Scalp hair shape	3.000000e-119
GCST003475_4	Beard thickness	1.000000e-15
GCST003477_5	Monobrow thickness	1.000000e-07
GCST012597_8	Attention deficit hyperactivity disorder	2.000000e-06

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D004476	Ectodermal Dysplasia	C16.131.077.350; C16.131.831.350; C16.320.850.250; C17.800.804.350; C17.800.827.250
D053360	Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive	C16.131.077.350.348; C16.131.831.350.348; C16.320.850.250.348; C17.800.804.350.348; C17.800.827.250.348
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020513	Paralysis, Hyperkalemic Periodic	C05.651.701.600; C10.668.491.650.600; C16.320.565.618.711.600; C18.452.648.618.711.600
C537250	Hemophagocytic lymphohistiocytosis, familial, 2 (supp.)
C531684	Hereditary spinal ataxia (supp.)
C567635	Hypokalemic Periodic Paralysis, Type 2 (supp.)
C538353	Potassium aggravated myotonia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066882 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	increases abundance, increases expression, decreases expression	2
Arsenic	increases expression, increases response to substance, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases methylation, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
tetrahydropalmatine	decreases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
coumarin	affects phosphorylation	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
Rosiglitazone	decreases reaction, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Pioglitazone	decreases reaction, increases expression	1
Troglitazone	decreases reaction, increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Azacitidine	increases expression	1
Cadmium	increases abundance, increases 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
CHEMBL5652233	Binding	Binding affinity to human RANBP2 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2DD	Abcam HeLa RANBP2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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