RANBP1

Summary

RANBP1 (RAN binding protein 1, HGNC:9847) is a protein-coding gene on chromosome 22q11.21, encoding Ran-specific GTPase-activating protein (P43487). Plays a role in RAN-dependent nucleocytoplasmic transport. It is a selective cancer dependency (DepMap: 34.4% of cell lines).

This gene encodes a protein that forms a complex with Ras-related nuclear protein (Ran) and metabolizes guanoside triphosphate (GTP). This complex participates in the regulation of the cell cycle by controlling transport of proteins and nucleic acids into the nucleus. There are multiple pseudogenes for this gene on chromosomes 9, 12, 17, and X. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5902 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total — 2 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 34.4% of screened cell lines
• MANE Select transcript: NM_001278639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9847
Approved symbol	RANBP1
Name	RAN binding protein 1
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	HTF9A
Ensembl gene	ENSG00000099901
Ensembl biotype	protein_coding
OMIM	601180
Entrez	5902

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000331821, ENST00000402752, ENST00000411892, ENST00000416427, ENST00000418705, ENST00000421656, ENST00000423859, ENST00000430524, ENST00000435265, ENST00000448394, ENST00000467920, ENST00000486575, ENST00000488484, ENST00000856544

RefSeq mRNA: 4 — MANE Select: NM_001278639 NM_001278639, NM_001278640, NM_001278641, NM_002882

CCDS: CCDS13775, CCDS63408, CCDS74823

Canonical transcript exons

ENST00000430524 — 6 exons

Exon	Start	End
ENSE00000650881	20126303	20126368
ENSE00003484108	20125308	20125436
ENSE00003543626	20122264	20122421
ENSE00003568790	20119013	20119149
ENSE00003712777	20126952	20127355
ENSE00003848803	20116104	20116430

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.6209 / max 574.9946, expressed in 1821 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191113	78.5597	1819
191112	12.2641	1644
191114	1.9263	676
191111	0.8708	498
209396	0.8406	504
209394	0.4250	214
191116	0.2827	95
209395	0.2594	105
191115	0.0869	40
191109	0.0616	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.95	gold quality
embryo	UBERON:0000922	98.93	gold quality
ventricular zone	UBERON:0003053	98.84	gold quality
left testis	UBERON:0004533	98.65	gold quality
right testis	UBERON:0004534	98.61	gold quality
testis	UBERON:0000473	97.75	gold quality
mucosa of transverse colon	UBERON:0004991	97.53	gold quality
cortical plate	UBERON:0005343	96.97	gold quality
prefrontal cortex	UBERON:0000451	96.73	gold quality
cerebellar hemisphere	UBERON:0002245	96.73	gold quality
cerebellar cortex	UBERON:0002129	96.72	gold quality
anterior cingulate cortex	UBERON:0009835	96.71	gold quality
cingulate cortex	UBERON:0003027	96.68	gold quality
left uterine tube	UBERON:0001303	96.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.67	gold quality
ectocervix	UBERON:0012249	96.59	gold quality
esophagus mucosa	UBERON:0002469	96.55	gold quality
right adrenal gland	UBERON:0001233	96.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.41	gold quality
body of uterus	UBERON:0009853	96.35	gold quality
vermiform appendix	UBERON:0001154	96.30	gold quality
thymus	UBERON:0002370	96.28	gold quality
left adrenal gland cortex	UBERON:0035825	96.25	gold quality
right frontal lobe	UBERON:0002810	96.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.24	gold quality
left adrenal gland	UBERON:0001234	96.23	gold quality
right lobe of liver	UBERON:0001114	96.20	gold quality
right adrenal gland cortex	UBERON:0035827	96.19	gold quality
esophagus	UBERON:0001043	96.17	gold quality
adrenal tissue	UBERON:0018303	96.16	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	1112.32
E-HCAD-10	yes	982.27
E-MTAB-6911	yes	834.72
E-MTAB-8271	yes	753.50
E-GEOD-125970	yes	468.73
E-HCAD-4	yes	149.01
E-HCAD-8	yes	53.34
E-HCAD-5	yes	35.62
E-CURD-122	yes	24.08
E-CURD-46	yes	23.99
E-HCAD-13	yes	22.97
E-MTAB-9067	yes	21.34
E-HCAD-1	yes	19.05
E-CURD-112	yes	10.72
E-MTAB-10553	yes	8.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, XBP1

miRNA regulators (miRDB)

49 targeting RANBP1, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-584-3P	99.35	67.69	1082

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• structure of the Ran-RanBP1-RanGAP complex (PMID:14585972)
• Phosphorylated wild type RanGAP1, but not a mutant harboring a mutation at the phosphorylation site 358S, efficiently formed a stable ternary complex with Ran and RanBP1 in vivo, suggesting that the 358S phosphorylation of RanGAP1 affects the Ran system. (PMID:16428860)
• These data indicate that RANBP1 activity is required for the proper localization of specific factors that regulate microtubule function; loss of this activity contributes to the generation of aneuploidy in a microtubule-dependent manner. (PMID:17940066)
• RanBP1-interfered cells show an increased apoptotic response to taxol compared to their counterpart with normal or high RanBP1 levels, and this response is caspase-3 dependent. (PMID:19270727)
• Generation of Ran-GTP from Ran-GDP by importin-beta is activated by Ran-binding protein-1 (RanBP1) that forms a trimeric complex with Ran-GDP and importin-beta. (PMID:19549784)
• Downregulation of the Ran GTPase effector RanBP1 is required for nuclear reorganisation. (PMID:20658144)
• RANBP1 on 22q11.21 locus might be causally related to the smooth pursuit eye movement abnormality rather than the development of schizophrenia. (PMID:21184585)
• in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis, is demonstrated. (PMID:21813642)
• Sgk1-dependent regulation of RANBP1 has functional consequences on both mitotic microtubule activity and taxol sensitivity of cancer cells. (PMID:23108393)
• RanBP1 controls the Ran pathway in mammalian cells through regulation of mitotic RCC1 dynamics. (PMID:32594833)
• CD147 supports paclitaxel resistance via interacting with RanBP1. (PMID:34974521)
• RanBP1: A Potential Therapeutic Target for Cancer Stem Cells in Lung Cancer and Glioma. (PMID:37047826)
• Oxidative stress and signaling through EGFR and PKA pathways converge on the nuclear transport factor RanBP1. (PMID:38011756)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ranbp1	ENSMUSG00000005732
rattus_norvegicus	Ranbp1	ENSRNOG00000001884
rattus_norvegicus	Ranbp1l1	ENSRNOG00000023917
drosophila_melanogaster	Nup358	FBGN0039302
caenorhabditis_elegans		WBGENE00003795

Paralogs (10): RGPD5 (ENSG00000015568), RANBP3 (ENSG00000031823), RGPD3 (ENSG00000153165), RANBP2 (ENSG00000153201), RANBP3L (ENSG00000164188), RGPD8 (ENSG00000169629), RGPD6 (ENSG00000183054), RGPD2 (ENSG00000185304), RGPD1 (ENSG00000187627), RGPD4 (ENSG00000196862)

Protein

Protein identifiers

Ran-specific GTPase-activating protein — P43487 (reviewed: P43487)

Alternative names: Ran-binding protein 1

All UniProt accessions (8): P43487, A0A140VK94, A0AA34QVZ7, C9JGV6, C9JIC6, C9JXG8, F6WQW2, F8WCY3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in RAN-dependent nucleocytoplasmic transport. Alleviates the TNPO1-dependent inhibition of RAN GTPase activity and mediates the dissociation of RAN from proteins involved in transport into the nucleus. Induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Promotes the disassembly of the complex formed by RAN and importin beta. Promotes dissociation of RAN from a complex with KPNA2 and CSE1L. Required for normal mitotic spindle assembly and normal progress through mitosis via its effect on RAN. Does not increase the RAN GTPase activity by itself, but increases GTP hydrolysis mediated by RANGAP1. Inhibits RCC1-dependent exchange of RAN-bound GDP by GTP.

Subunit / interactions. Interacts with RAN (via C-terminus of GTP-bound form) but not with GDP-bound RAN. Identified in a complex composed of RAN, RANGAP1 and RANBP1. Identified in a complex that contains TNPO1, RAN and RANBP1. Identified in a complex that contains CSE1L, KPNA2, RAN and RANBP1. Identified in a complex with nucleotide-free RAN and RCC1.

Similarity. Belongs to the RANBP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P43487-1	1	yes
P43487-2	2

RefSeq proteins (4): NP_001265568, NP_001265569, NP_001265570, NP_002873 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000156	Ran_bind_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR045255	RanBP1-like	Family
IPR045256	RanBP1_RanBD	Domain

Pfam: PF00638

UniProt features (29 total): modified residue 9, strand 7, sequence variant 2, region of interest 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1, sequence conflict 1, domain 1, turn 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9N85	ELECTRON MICROSCOPY	2.6
1K5D	X-RAY DIFFRACTION	2.7
1K5G	X-RAY DIFFRACTION	3.1
9YB5	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43487-F1	84.05	0.62

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): 60, 150, 150, 183, 188, 190, 2, 13, 18, 21

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-165054	Rev-mediated nuclear export of HIV RNA

MSigDB gene sets: 345 (showing top): GNF2_CKS1B, RNGTGGGC_UNKNOWN, E2F_Q4, E2F_Q4_01, PAX4_01, E2F4DP1_01, GAANYNYGACNY_UNKNOWN, CMYB_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, MORF_HDAC2, GOMF_GTPASE_BINDING, PUJANA_CHEK2_PCC_NETWORK, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP

GO Biological Process (5): nucleocytoplasmic transport (GO:0006913), signal transduction (GO:0007165), positive regulation of mitotic centrosome separation (GO:0046604), spindle organization (GO:0007051), intracellular transport (GO:0046907)

GO Molecular Function (5): GDP-dissociation inhibitor activity (GO:0005092), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Late Phase of HIV Life Cycle	1
Interactions of Rev with host cellular proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
GTPase regulator activity	2
cellular anatomical structure	2
nuclear transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
mitotic centrosome separation	1
regulation of mitotic centrosome separation	1
positive regulation of cell cycle process	1
microtubule cytoskeleton organization	1
cell cycle process	1
transport	1
cellular localization	1
establishment of localization in cell	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
GTPase binding	1
cell adhesion molecule binding	1
binding	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
nuclear protein-containing complex	1
centriole	1
microtubule organizing center	1
cytoplasm	1

Protein interactions and networks

STRING

2924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RANBP1	RANGAP1	P46060	998
RANBP1	RAN	P17080	989
RANBP1	RANBP3	Q9H6Z4	957
RANBP1	TRMT2A	Q8IZ69	929
RANBP1	RCC1	P18754	912
RANBP1	NUTF2	P13662	908
RANBP1	RANGRF	Q9HD47	864
RANBP1	IPO8	O15397	805
RANBP1	GNB1L	Q9BYB4	786
RANBP1	XPO1	O14980	772
RANBP1	PPP4R3B	Q5MIZ7	745
RANBP1	IPO7	O95373	730
RANBP1	PPP4R3A	Q6IN85	719
RANBP1	CSE1L	P55060	690
RANBP1	NUP62	P37198	690

IntAct

124 interactions, top by confidence:

A	B	Type	Score
PDLIM1	ACTN4	psi-mi:“MI:0914”(association)	0.800
RAN	RANBP1	psi-mi:“MI:0407”(direct interaction)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
LRRK2	DFFA	psi-mi:“MI:0914”(association)	0.530
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
RAN	rna1	psi-mi:“MI:0915”(physical association)	0.400
Ranbp2		psi-mi:“MI:0915”(physical association)	0.400
NUPR1	RANBP1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Rcc1	WDR46	psi-mi:“MI:0914”(association)	0.350
Tubg1	ZC3H18	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
	TUBA4A	psi-mi:“MI:0914”(association)	0.350
LACC1	FLJ10842	psi-mi:“MI:0914”(association)	0.350
M	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
M2	IPO5	psi-mi:“MI:0914”(association)	0.350
PHOSPHO1	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (290): RANBP1 (Two-hybrid), HERC5 (Affinity Capture-Western), RANBP1 (Affinity Capture-MS), ATP6V1D (Co-fractionation), GOLPH3 (Co-fractionation), RAB1A (Co-fractionation), RAN (Co-fractionation), RANBP1 (Co-fractionation), RANBP1 (Co-fractionation), RANBP1 (Co-fractionation), RANBP3L (Co-fractionation), TARDBP (Co-fractionation), RANBP1 (Affinity Capture-MS), RANBP1 (Proximity Label-MS), RANBP1 (Affinity Capture-MS)

ESM2 similar proteins: A9YUB1, O13923, P05455, P09874, P10711, P10881, P11103, P18493, P20232, P23193, P26043, P26044, P26446, P27008, P28000, P28048, P28049, P31669, P34022, P35189, P35241, P41920, P43487, P48598, P55010, P59325, P87058, P92985, Q02790, Q06068, Q07205, Q09717, Q0IJ05, Q29RL9, Q32LP2, Q3T0M7, Q4KLL0, Q54KD9, Q5R4L0, Q5RD91

Diamond homologs: A0A0B4K7J2, A6NKT7, E9Q3G8, H2QII6, O14715, P0DJD0, P0DJD1, P34022, P40517, P41920, P43487, P92985, Q09717, Q3T0M7, Q54KD9, Q7Z3J3, Q8RWG8, Q99666, Q9C829, Q9LMK7, Q9USL4, D3ZZL9, P32499, P34562, P48820, P49792, Q8CHG3, Q8IWJ2, Q9ERU9, G0SDP9, G0S8I1, Q09146, Q4R4T9, Q5R4Y2, Q9CT10, Q9H6Z4, Q6PDH4, Q9LW88

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PLK1	“up-regulates activity”	RANBP1	phosphorylation

Enriched among interaction partners

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

Reactome pathways:

Pathway	Partners	Fold	FDR
Apoptotic execution phase	6	30.1×	2e-05
Nuclear import of Rev protein	5	17.7×	1e-03
Degradation of CDH1	6	12.4×	1e-03
Apoptosis	7	12.4×	4e-04
Activation of STAT3 by cadherin engagement	7	12.0×	4e-04
Programmed Cell Death	7	10.8×	7e-04
Regulation of RAS by GAPs	5	10.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of innate immune response	5	22.4×	1e-03
protein import into nucleus	9	11.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	41
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1703642	GRCh37/hg19 22q11.21(chr22:18644790-21800471)	Pathogenic
636281	GRCh37/hg19 22q11.21(chr22:18631364-21800471)x1	Pathogenic

SpliceAI

1678 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20116032:ACTC:A	donor_loss	1.0000
22:20116034:TCAC:T	donor_loss	1.0000
22:20116035:CA:C	donor_loss	1.0000
22:20116036:A:AC	donor_gain	1.0000
22:20116036:ACTTG:A	donor_loss	1.0000
22:20116037:C:CT	donor_gain	1.0000
22:20116037:CTTGG:C	donor_gain	1.0000
22:20119007:CCACA:C	acceptor_loss	1.0000
22:20119009:ACAG:A	acceptor_gain	1.0000
22:20119011:A:AG	acceptor_gain	1.0000
22:20119011:AG:A	acceptor_gain	1.0000
22:20119011:AGG:A	acceptor_loss	1.0000
22:20119012:G:GT	acceptor_gain	1.0000
22:20119012:GG:G	acceptor_gain	1.0000
22:20119012:GGA:G	acceptor_gain	1.0000
22:20119012:GGAC:G	acceptor_gain	1.0000
22:20119012:GGACA:G	acceptor_gain	1.0000
22:20119145:AAAAT:A	donor_gain	1.0000
22:20119146:AAAT:A	donor_gain	1.0000
22:20119147:AAT:A	donor_gain	1.0000
22:20119148:AT:A	donor_gain	1.0000
22:20119148:ATG:A	donor_loss	1.0000
22:20119150:GTAA:G	donor_gain	1.0000
22:20119153:A:AG	donor_gain	1.0000
22:20119154:G:GG	donor_gain	1.0000
22:20122259:TGCA:T	acceptor_loss	1.0000
22:20122260:GCAG:G	acceptor_loss	1.0000
22:20122261:CAG:C	acceptor_loss	1.0000
22:20122262:A:AG	acceptor_gain	1.0000
22:20122262:AG:A	acceptor_gain	1.0000

AlphaMissense

1828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20122275:T:C	L55P	1.000
22:20122310:T:A	W67R	1.000
22:20122310:T:C	W67R	1.000
22:20122312:G:C	W67C	1.000
22:20122312:G:T	W67C	1.000
22:20122322:G:C	G71R	1.000
22:20122323:G:A	G71D	1.000
22:20122328:G:C	G73R	1.000
22:20122329:G:A	G73D	1.000
22:20122329:G:T	G73V	1.000
22:20122335:T:A	V75D	1.000
22:20122344:T:C	L78P	1.000
22:20122380:T:C	M90T	1.000
22:20122386:G:T	R92M	1.000
22:20122407:G:A	C99Y	1.000
22:20122408:T:G	C99W	1.000
22:20122410:C:A	A100D	1.000
22:20125361:T:A	W122R	1.000
22:20125361:T:C	W122R	1.000
22:20125413:C:A	A139D	1.000
22:20125422:T:C	F142S	1.000
22:20119076:T:C	F27L	0.999
22:20119078:T:A	F27L	0.999
22:20119078:T:G	F27L	0.999
22:20122268:G:C	A53P	0.999
22:20122269:C:A	A53E	0.999
22:20122273:A:C	K54N	0.999
22:20122273:A:T	K54N	0.999
22:20122275:T:A	L55Q	0.999
22:20122281:G:C	R57P	0.999

dbSNP variants (sampled 300 via entrez): RS1000071889 (22:20120598 C>T), RS1000172388 (22:20117260 C>A), RS1000499497 (22:20127350 C>A,T), RS1001019119 (22:20116097 A>G), RS1001115998 (22:20121854 T>G), RS1001520635 (22:20120035 T>C), RS1001704629 (22:20125601 C>A,T), RS1001717454 (22:20123195 G>A), RS1001770206 (22:20118049 C>G,T), RS1001978951 (22:20119270 G>A), RS1002083227 (22:20122894 G>C), RS1002133449 (22:20119017 C>G), RS1002155247 (22:20125853 A>C), RS1002282793 (22:20124816 G>C), RS1002288415 (22:20114416 G>A)

Disease associations

OMIM: gene MIM:601180 | disease phenotypes: MIM:188400, MIM:192430

GenCC curated gene-disease

Mondo (2): DiGeorge syndrome (MONDO:0008564), velocardiofacial syndrome (MONDO:0008644)

Orphanet (1): 22q11.2 deletion syndrome (Orphanet:567)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066219 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 341 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4297623	ELTANEXOR	2	341

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.26	IC50	550	nM	ELTANEXOR
6.21	IC50	620	nM	CHEMBL6142071
5.44	Kd	3628	nM	CHEMBL3752910
5.44	ED50	3628	nM	CHEMBL3752910
5.09	Kd	8144	nM	CHEMBL5653589
5.09	ED50	8144	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149190: Binding affinity to human RANBP1 incubated for 45 mins by Kinobead based pull down assay	kd	3.6275	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149190: Binding affinity to human RANBP1 incubated for 45 mins by Kinobead based pull down assay	kd	8.1441	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
bisphenol A	affects expression, decreases expression	3
Benzo(a)pyrene	decreases expression	2
Copper	affects binding, decreases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Nickel	increases expression	2
Dronabinol	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
abemaciclib	decreases expression	1
bisphenol F	increases expression	1
TAK-243	affects sumoylation	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases expression, increases abundance	1
sulindac sulfide	increases expression	1
ochratoxin A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
quinoline	decreases expression	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
avobenzone	increases expression	1
bicalutamide	decreases expression	1
phenethyl isothiocyanate	affects binding	1
chromium hexavalent ion	increases abundance, decreases expression	1
chloropicrin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
sulphoraphene	affects localization	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5526700	Binding	Inhibition of RANBP1 nuclear export in human U2OS cells at 41 to 10000 nM measured for 6 hrs by DAPI staining based immunofluorescence analysis	Electrophile Determines Cellular Phenotypes among XPO1-Targeting Small Molecules. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B3FR	Abcam HEK293T RANBP1 KO	Transformed cell line	Female
CVCL_E4Q3	KOLF2.1J RANBP1 7.5kbdel DEL/DEL	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00768820	PHASE4	RECRUITING	The Psychiatric and Cognitive Phenotypes in Velocardiofacial Syndrome
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT05290493	PHASE2	COMPLETED	NB-001 in Children and Adolescents With 22q11 Deletion Syndrome
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT00849888	PHASE1	TERMINATED	Serum-Free Thymus Transplantation in DiGeorge Anomaly
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT00579527	PHASE1/PHASE2	COMPLETED	Phase I/II Thymus Transplantation With Immunosuppression #950
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
NCT00278005	Not specified	TERMINATED	Infection in DiGeorge Following CHD Surgery
NCT00556530	Not specified	RECRUITING	Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome
NCT00916955	Not specified	COMPLETED	Genetic Modifiers for 22q11.2 Syndrome
NCT01220531	Not specified	COMPLETED	Thymus Transplantation Safety-Efficacy
NCT01781923	Not specified	COMPLETED	Cognitive Remediation in 22q11DS
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02430584	Not specified	UNKNOWN	Whole Blood Specimen Collection From Pregnant Subjects
NCT02460328	Not specified	COMPLETED	Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome
NCT02787486	Not specified	COMPLETED	Expanded Noninvasive Genomic Medical Assessment: The Enigma Study
NCT03284060	Not specified	TERMINATED	Social Cognition Training and Cognitive Remediation
NCT04141540	Not specified	COMPLETED	Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11
NCT04373226	Not specified	TERMINATED	Arithmetic Abilities in Children With 22q11.2DS
NCT04639388	Not specified	RECRUITING	Understanding of Psychotic Disorders in Children With 22q11.2DS
NCT04639960	Not specified	TERMINATED	Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
NCT04647500	Not specified	COMPLETED	Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
NCT05924347	Not specified	RECRUITING	Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders
NCT02070211	PHASE2/PHASE3	UNKNOWN	Indicated Prevention With Long-chain Polyunsaturated Omega-3 Fatty Acids in Patients With 22q11 Microdeletion Syndrome.
NCT00917189	Not specified	COMPLETED	Computerized Cognitive Skills Training for Adolescents With Velocardiofacial Syndrome
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT05664412	Not specified	RECRUITING	Using Transcranial Alternating Current Stimulation to Improve Executive Function in 22q11.2 Deletion Syndrome
NCT05849441	Not specified	COMPLETED	Mindfulness Program for Adolescents With 22q11DS