RANBP9

Summary

RANBP9 (RAN binding protein 9, HGNC:13727) is a protein-coding gene on chromosome 6p23, encoding Ran-binding protein 9 (Q96S59). May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways.

This gene encodes a protein that binds RAN, a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The protein encoded by this gene has also been shown to interact with several other proteins, including met proto-oncogene, homeodomain interacting protein kinase 2, androgen receptor, and cyclin-dependent kinase 11.

Source: NCBI Gene 10048 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_005493

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13727
Approved symbol	RANBP9
Name	RAN binding protein 9
Location	6p23
Locus type	gene with protein product
Status	Approved
Aliases	RanBPM
Ensembl gene	ENSG00000010017
Ensembl biotype	protein_coding
OMIM	603854
Entrez	10048

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000011619, ENST00000469916, ENST00000940147, ENST00000940148, ENST00000940149, ENST00000962251

RefSeq mRNA: 1 — MANE Select: NM_005493 NM_005493

CCDS: CCDS4529

Canonical transcript exons

ENST00000011619 — 14 exons

Exon	Start	End
ENSE00000848070	13639563	13639753
ENSE00001009197	13652659	13652681
ENSE00001009198	13641199	13641307
ENSE00001009205	13642479	13642591
ENSE00001009209	13637808	13637955
ENSE00001009216	13621498	13622492
ENSE00001009217	13634431	13634552
ENSE00001009219	13632370	13632521
ENSE00001141779	13696785	13696896
ENSE00001815244	13710935	13711835
ENSE00003505270	13625653	13625764
ENSE00003565295	13658780	13658832
ENSE00003712108	13644545	13644729
ENSE00003714478	13657109	13657276

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.9962 / max 342.1206, expressed in 1820 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71851	11.3714	1785
71849	3.4082	1506
71845	1.6711	955
71850	1.2932	888
71841	1.2722	704
71848	1.0332	638
71846	0.9337	551
71853	0.9178	518
71847	0.8154	454
71852	0.5324	289

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.81	gold quality
secondary oocyte	CL:0000655	99.61	gold quality
male germ cell	CL:0000015	99.55	gold quality
esophagus squamous epithelium	UBERON:0006920	99.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.31	gold quality
epithelium of esophagus	UBERON:0001976	99.22	gold quality
endothelial cell	CL:0000115	99.21	gold quality
squamous epithelium	UBERON:0006914	99.17	gold quality
cervix squamous epithelium	UBERON:0006922	99.16	gold quality
amniotic fluid	UBERON:0000173	99.08	gold quality
tongue squamous epithelium	UBERON:0006919	99.07	gold quality
oocyte	CL:0000023	98.94	gold quality
oral cavity	UBERON:0000167	98.68	gold quality
pharyngeal mucosa	UBERON:0000355	98.55	gold quality
upper leg skin	UBERON:0004262	98.47	gold quality
penis	UBERON:0000989	98.46	gold quality
adult organism	UBERON:0007023	98.42	gold quality
gingiva	UBERON:0001828	98.41	gold quality
gingival epithelium	UBERON:0001949	98.41	gold quality
epithelium of nasopharynx	UBERON:0001951	98.35	gold quality
lower esophagus mucosa	UBERON:0035834	98.25	gold quality
tibia	UBERON:0000979	97.83	gold quality
skin of hip	UBERON:0001554	97.73	gold quality
substantia nigra pars compacta	UBERON:0001965	97.71	gold quality
pancreatic ductal cell	CL:0002079	97.69	gold quality
choroid plexus epithelium	UBERON:0003911	97.63	gold quality
cervix epithelium	UBERON:0004801	97.62	gold quality
body of tongue	UBERON:0011876	97.55	gold quality
tongue	UBERON:0001723	97.48	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.89
E-MTAB-7303	no	178.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting RANBP9, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Literature-anchored findings (GeneRIF, showing 40)

• RanBPM is the enzymic substrate for USP11 and is deubiquitinated specifically (PMID:12084015)
• RANBPM has a role in the HGF-MET and Ras signal transduction pathways (PMID:12147692)
• overexpressed wildtype HIPK2 and a kinase defective mutant of HIPK2 directly interact with RanBPM in the nucleus of mammalian cells. (PMID:12220523)
• interacts with steroid receptors to selectively modify their activity (PMID:12361945)
• demonstrates that CDK11(p46) directly interacts with RanBPM in vitro and in human cells (PMID:14511641)
• RanBPM may constitute a molecular scaffold that contributes to coupling LFA-1 and other integrins with intracellular signaling pathways (PMID:14722085)
• Expression of RanBPM inhibited the ubiquitination of p73alpha, and thereby prolonged its half-life. (PMID:15558019)
• Results identify and characterise a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. (PMID:15964779)
• Coexpression of RANBP9 with constitutively active Raf kinase synergistically inhibited myogenic regulatory factor MyoD-directed muscle reporter gene transcription (PMID:16364241)
• CD39 associations with RanBPM have the potential to regulate NTPDase catalytic activity. This intermolecular interaction may have important implications for the regulation of extracellular nucleotide-mediated signalling. (PMID:16478441)
• RanBPM is a potent novel coactivator for thyroid hormone receptors (PMID:16595702)
• RanBPM, ARMC8alpha, ARMC8beta, Muskelin, p48EMLP, and p44CTLH form complexes in cells (PMID:17467196)
• Studies in this review indicate that RanBPM acts as a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. (PMID:18040864)
• RanBPM co-localizes with p42IP4 and, together with p42(IP4), the SPRY domain of RanBPM could act as a modulator of synaptic plasticity. (PMID:18298663)
• Results describe the enhancement of the transactivation activity of Epstein-Barr virus Rta protein by RanBPM. (PMID:18455188)
• These novel findings identify a role for muskelin-RanBP9 complex in pathways that integrate cell morphology regulation and nucleocytoplasmic communication. (PMID:18710924)
• These results suggest that RanBPM could be a key regulator of Ca(v)3.1 channel-mediated signaling pathways. (PMID:18801335)
• Overexpression of RanBP9 resulted in the enhancement of APP interactions with LRP and BACE1 and increased lipid raft association of APP. (PMID:19251705)
• RanBP9-N60, a processed form of RanBP9 virtually identical to the RanBP9-Delta1/N60 mutant, was strongly increased in Alzheimer disease brains compared with controls. (PMID:19729516)
• results indicate that RanBPM, potentially through interaction with citron kinase, plays a role in the progression of neocortical precursors through M-phase at the ventricular surface. (PMID:19790105)
• These results reveal a novel proapoptotic function for RanBPM in DNA damage-induced apoptosis through the regulation of factors involved in the mitochondrial apoptotic pathway. (PMID:19996306)
• data support the idea that RanBP9 and RanBP10 may function as signaling integrators and dictate the efficient regulation of D(1) receptor signaling by PKCdelta and PKCgamma (PMID:20395553)
• RanBPM may modulate TrkB-mediated downstream signaling and biological functions. (PMID:20403074)
• RanBPM influences TRAF6 ubiquitination and the TRAF6-triggered NF-kappaB signaling pathway through RanBPM’s interaction with TRAF6. These data suggest that RanBPM participates in gene transcription by binding to TRAF6. (PMID:21805090)
• Data indicate that RanBP9 simultaneously inhibits cell-adhesive processes and enhances Abeta generation by accelerating APP, LRP, and beta1-integrin endocytosis. (PMID:22223749)
• COPS5 is a novel RanBP9-binding protein that increases APP processing and Abeta generation by stabilizing RanBP9 protein levels (PMID:23926111)
• RanBPM acts as a negative regulator of BLT2 signaling to attenuate BLT2-mediated cell motility (PMID:23928309)
• RanBP9 transgene overexpression causes early synaptic deficits, impaired learning and accelerates amyloid plaque accumulation. (PMID:24254706)
• RanBP9 relocates APP intracellular domain to Tip60-enriched nuclear speckles and prevented the formation of nuclear spots formation; results place RanBP9 as an important player in the multiple steps of AbetaPP signaling (PMID:25024339)
• association analyses between RANBP9 variants and the risk of schizophrenia were conducted, however no significant association was identified. (PMID:25482375)
• these analyses reveal that RanBPM subcellular localization results from the combined effects of several elements that either confer direct transport through the nucleocytoplasmic transport machinery (PMID:25659156)
• RanBPM was found to enhance Zta-dependent transcriptional activity via the inhibition of Zta sumoylation. (PMID:25900136)
• High RANBPM expression is associated with cancer. (PMID:26919101)
• RanBP9 absence hampers the molecular mechanisms leading to efficient repair of damaged DNA, resulting in enhanced sensitivity to genotoxic stress. (PMID:26943034)
• Loss of RanBPM expression may play an important role in gastric cancer tumor development and metastasis. Reduced RanBPM expression is also associated with chemoresistance of gastric cancer cells. (PMID:26977028)
• RanBP9 is positively expressed in bone tumor tissues and cell strains. (PMID:27049080)
• The 20-mer peptide (residues 228-247) of human DDX-4, an ATP-dependent RNA helicase known to regulate germ cell development, binds to a unique shallow binding surface on RanBPM formed by highly conserved loops on the surface of the beta-sheet with two aspartates on one end, a positive patch on the opposite end, and a tryptophan lining at the bottom of the surface. (PMID:27622290)
• RanBPM acts as a negative regulator of BLT2 and IL8, thus attenuating the invasiveness of aggressive breast cancer cells (PMID:28027932)
• RanBP9/TSSC3 complex cooperatively suppress metastasis via downregulation of Src-dependent Akt pathway to expedite mitochondrial-associated anoikis. (PMID:28032865)
• Ran binding protein 9(RanBPM) is a scaffolding protein with a modulatory function that regulates the activities of IFN-stimulated response elements. IFN-lambda1 affects the cellular distribution of RanBPM and stimulates the interaction between RanBPM and interferon, lambda receptor 1(IFN-lambdaR1). Therefore, RanBPM plays a novel role in the IFN-lambda-regulated signaling pathway. (PMID:28547582)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ranbp9	ENSDARG00000061048
mus_musculus	Ranbp9	ENSMUSG00000038546
rattus_norvegicus	Ranbp9	ENSRNOG00000017951
drosophila_melanogaster	RanBPM	FBGN0262114

Paralogs (3): GID8 (ENSG00000101193), RANBP10 (ENSG00000141084), SPRYD3 (ENSG00000167778)

Protein

Protein identifiers

Ran-binding protein 9 — Q96S59 (reviewed: Q96S59)

Alternative names: BPM-L, BPM90, Ran-binding protein M, RanBP7

All UniProt accessions (1): Q96S59

UniProt curated annotations — full annotation on UniProt →

Function. May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways. Acts as a mediator of cell spreading and actin cytoskeleton rearrangement. Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA.

Subunit / interactions. Part of a complex consisting of RANBP9, MKLN1 and GID8. Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with GTP-bound Ran, AR, CDC2L1/p110C, CALB1, S100A7, USP11, MKLN1, SOS1 or SOS2, GID8, and FMR1. Interacts with the Dyrk kinases HIPK2, DYRK1A, and DYRK1B. Interacts with TP73 isoform Alpha but not with TP53. Interacts with the HGF receptor MET and the integrins ITGB1 and ITGB2, but not with ITGAL. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Directly interacts with RANBP10. Interacts with YPEL5. Interacts with DDX4. Interacts with NGFR. Interacts with TEX19.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Ubiquitously expressed, with highest levels in testes, placenta, heart, and muscle, and lowest levels in lung. Within the brain, expressed predominantly by neurons in the gray matter of cortex, the granular layer of cerebellum and the Purkinje cells.

Post-translational modifications. Phosphorylated in response to stress. Can be phosphorylated by the cleaved p110 form of CDC2L1 (p110C). Ubiquitinated. Polyubiquitination targets the protein for rapid degradation via the ubiquitin system. Can be deubiquitinated by USP11.

Domain organisation. The SPRY domain mediates the interaction with MET, AR, and CDC2L1.

Similarity. Belongs to the RANBP9/10 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96S59-1	1	yes
Q96S59-2	2
Q96S59-3	3

RefSeq proteins (1): NP_005484* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR006594	LisH	Conserved_site
IPR006595	CTLH_C	Domain
IPR013144	CRA_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR024964	CTLH/CRA	Domain
IPR035782	SPRY_RanBP9/10	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050618	Ubq-SigPath_Reg	Family

Pfam: PF00622, PF08513, PF10607

UniProt features (49 total): strand 15, helix 9, compositionally biased region 6, turn 5, region of interest 4, domain 3, modified residue 3, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5JI7	X-RAY DIFFRACTION	1.51
5JIU	X-RAY DIFFRACTION	2.05
5JI9	X-RAY DIFFRACTION	2.5
7NSC	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S59-F1	73.43	0.52

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 (3): 405, 477, 487

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-373760	L1CAM interactions
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-8851805	MET activates RAS signaling
R-HSA-9861718	Regulation of pyruvate metabolism

MSigDB gene sets: 263 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, DITTMER_PTHLH_TARGETS_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TACAATC_MIR508, GOBP_MICROTUBULE_NUCLEATION, GOMF_GTPASE_BINDING, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_AMYLOID_PRECURSOR_PROTEIN_CATABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, TGCTGAY_UNKNOWN, GTGTTGA_MIR505, ATTACAT_MIR3803P, DEN_INTERACT_WITH_LCA5, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS

GO Biological Process (5): cytoskeleton organization (GO:0007010), microtubule nucleation (GO:0007020), protein-containing complex assembly (GO:0065003), negative regulation of ERK1 and ERK2 cascade (GO:0070373), positive regulation of amyloid precursor protein catabolic process (GO:1902993)

GO Molecular Function (3): enzyme binding (GO:0019899), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (9): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), nuclear body (GO:0016604), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Axon guidance	1
MAPK1/MAPK3 signaling	1
Signaling by MET	1
Pyruvate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
organelle organization	1
microtubule cytoskeleton organization	1
microtubule polymerization	1
cellular component assembly	1
protein-containing complex organization	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
amyloid precursor protein catabolic process	1
positive regulation of protein metabolic process	1
regulation of amyloid precursor protein catabolic process	1
protein binding	1
GTPase binding	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
microtubule cytoskeleton	1
protein-containing complex	1
membrane	1
cell periphery	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RANBP9	MKLN1	Q9UL63	993
RANBP9	RMND5A	Q9H871	960
RANBP9	MPHOSPH8	Q99549	929
RANBP9	AXL	P30530	831
RANBP9	GID8	Q9NWU2	759
RANBP9	ARMC8	Q8IUR7	734
RANBP9	YPEL5	P62699	721
RANBP9	NTRK1	P04629	720
RANBP9	GID4	Q8IVV7	716
RANBP9	WDR26	Q9H7D7	716
RANBP9	MAEA	Q7L5Y9	632
RANBP9	PLXNA1	Q9UIW2	576
RANBP9	NGFR	P08138	573
RANBP9	RMND5B	Q96G75	569
RANBP9	PLXNA3	P51805	559

IntAct

202 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
ARMC8	HTRA2	psi-mi:“MI:0914”(association)	0.750
RANBP9	OPRM1	psi-mi:“MI:0915”(physical association)	0.690
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
RANBP10	MAEA	psi-mi:“MI:0914”(association)	0.640
RANBP9	YPEL5	psi-mi:“MI:0914”(association)	0.640
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
PRG2	YPEL5	psi-mi:“MI:0914”(association)	0.640
DYRK1B	RANBP9	psi-mi:“MI:0915”(physical association)	0.630
RANBP9	DYRK1B	psi-mi:“MI:0407”(direct interaction)	0.630
DISC1	RANBP9	psi-mi:“MI:0915”(physical association)	0.630
RANBP9	DISC1	psi-mi:“MI:0915”(physical association)	0.630
GID8	HTRA2	psi-mi:“MI:0914”(association)	0.610
ITGB2	RANBP9	psi-mi:“MI:0915”(physical association)	0.610
RANBP9	ITGB2	psi-mi:“MI:0915”(physical association)	0.610
RANBP9	ITGB2	psi-mi:“MI:0407”(direct interaction)	0.610
RANBP9	ITGB2	psi-mi:“MI:0403”(colocalization)	0.610
RANBP9	MET	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (656): RANBP9 (Two-hybrid), RANBP9 (Affinity Capture-Western), RANBP9 (Two-hybrid), RANBP9 (Reconstituted Complex), RANBP9 (Two-hybrid), RANBP9 (Two-hybrid), RANBP9 (Two-hybrid), RANBP9 (Reconstituted Complex), RANBP9 (Two-hybrid), RANBP9 (Two-hybrid), RANBP9 (Affinity Capture-Western), OPRM1 (Affinity Capture-Western), RANBP9 (Affinity Capture-MS), RANBP9 (Affinity Capture-MS), RANBP9 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA8, A1A5P5, A1L252, A1YVX4, A3KMI0, A3KMV8, A6H8H2, F4HYD7, F4HYJ7, O73630, O94712, P29375, P41229, P41230, P69566, Q04861, Q1LUS8, Q28FM1, Q30DN6, Q32SG6, Q38JA7, Q3B8D5, Q3UXZ9, Q4R8E0, Q5F3R2, Q5U245, Q5VZ89, Q5XUN4, Q62240, Q63185, Q6IQX0, Q6P158, Q6P5D3, Q6VN19, Q6VN20, Q7Z3E5, Q7Z401, Q80Y84, Q94545, Q96S59

Diamond homologs: A0A5F9C6I2, A1L252, A2VD92, B0LPN4, D3ZXK7, E9PZQ0, E9Q401, F1LMY4, O94712, P11716, P16960, P21817, P30957, P69566, Q15413, Q19614, Q1LUS8, Q28FM1, Q5R881, Q5XH91, Q5XPI3, Q5XPI4, Q6VN19, Q8BVR6, Q90WU3, Q92736, Q95LP3, Q96DX4, Q96S59, Q9PTY5, Q9VNV3, A1CNW8, A1D1S7, A3KMV8, A6S3E0, A6ZZJ6, A7EQ00, A7TE03, O74497, P18160

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RANBP9	“down-regulates activity”	DYRK1B	binding
ATM	“up-regulates activity”	RANBP9	phosphorylation
MET	up-regulates	RANBP9	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
Regulation of pyruvate metabolism	9	40.5×	3e-10
Downregulation of TGF-beta receptor signaling	5	16.1×	3e-03
Pyruvate metabolism	5	16.1×	3e-03
Transcriptional Regulation by MECP2	5	12.5×	6e-03
Deubiquitination	7	6.8×	8e-03
Ub-specific processing proteases	11	4.6×	4e-03
Diseases of signal transduction by growth factor receptors and second messengers	10	4.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
reactive oxygen species metabolic process	5	14.8×	8e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	17	5.6×	2e-05
positive regulation of ERK1 and ERK2 cascade	10	5.4×	8e-03
negative regulation of cell population proliferation	14	3.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2563 predictions. Top by Δscore:

Variant	Effect	Δscore
6:13625647:ACTT:A	donor_loss	1.0000
6:13625648:CTT:C	donor_loss	1.0000
6:13625649:TTACC:T	donor_loss	1.0000
6:13625650:TA:T	donor_loss	1.0000
6:13625651:A:AC	donor_gain	1.0000
6:13625652:C:CC	donor_gain	1.0000
6:13632365:TTCA:T	donor_loss	1.0000
6:13632366:TCACC:T	donor_loss	1.0000
6:13632367:CA:C	donor_loss	1.0000
6:13632368:A:C	donor_loss	1.0000
6:13632369:C:CG	donor_loss	1.0000
6:13632371:TTCA:T	donor_gain	1.0000
6:13632417:G:C	donor_gain	1.0000
6:13632517:AACTT:A	acceptor_gain	1.0000
6:13632519:CTT:C	acceptor_gain	1.0000
6:13632520:TT:T	acceptor_gain	1.0000
6:13632522:C:CC	acceptor_gain	1.0000
6:13632523:T:G	acceptor_loss	1.0000
6:13634422:A:AC	donor_gain	1.0000
6:13634423:C:CC	donor_gain	1.0000
6:13634451:T:TA	donor_gain	1.0000
6:13634548:CATTA:C	acceptor_gain	1.0000
6:13634549:ATTA:A	acceptor_gain	1.0000
6:13634550:TTA:T	acceptor_gain	1.0000
6:13634550:TTAC:T	acceptor_loss	1.0000
6:13634551:TA:T	acceptor_gain	1.0000
6:13634551:TACTG:T	acceptor_loss	1.0000
6:13634553:C:CC	acceptor_gain	1.0000
6:13634553:CTGAA:C	acceptor_loss	1.0000
6:13634554:T:G	acceptor_loss	1.0000

AlphaMissense

4739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:13625655:A:G	L686S	1.000
6:13625658:A:C	I685R	1.000
6:13625658:A:G	I685T	1.000
6:13625658:A:T	I685K	1.000
6:13625662:C:G	A684P	1.000
6:13625666:G:C	N682K	1.000
6:13625666:G:T	N682K	1.000
6:13625670:A:G	L681P	1.000
6:13625670:A:T	L681H	1.000
6:13625690:T:A	R674S	1.000
6:13625690:T:G	R674S	1.000
6:13625691:C:G	R674T	1.000
6:13625706:A:G	L669P	1.000
6:13625743:A:C	Y657D	1.000
6:13625745:G:T	A656E	1.000
6:13625748:A:G	L655P	1.000
6:13625748:A:T	L655Q	1.000
6:13625751:A:C	L654R	1.000
6:13625751:A:G	L654P	1.000
6:13625751:A:T	L654Q	1.000
6:13625753:A:C	S653R	1.000
6:13625753:A:T	S653R	1.000
6:13625755:T:G	S653R	1.000
6:13625756:G:C	F652L	1.000
6:13625756:G:T	F652L	1.000
6:13625758:A:G	F652L	1.000
6:13625760:G:T	A651E	1.000
6:13632374:A:G	L648S	1.000
6:13632416:A:G	L634P	1.000
6:13632437:A:G	L627P	1.000

dbSNP variants (sampled 300 via entrez): RS1000006877 (6:13633652 A>T), RS1000007568 (6:13674618 G>A), RS1000025021 (6:13640343 G>A), RS1000121094 (6:13639062 C>T), RS1000144471 (6:13674943 T>A), RS1000200724 (6:13700648 TA>T), RS1000201671 (6:13663192 A>T), RS1000269220 (6:13700202 C>T), RS1000292408 (6:13710303 G>A), RS1000324763 (6:13623646 T>A,C), RS1000395041 (6:13691411 G>C), RS1000448896 (6:13629095 A>T), RS1000462945 (6:13710832 A>G), RS1000463040 (6:13679926 CA>C), RS1000480050 (6:13629328 A>G)

Disease associations

OMIM: gene MIM:603854 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001937_5	Breast cancer	8.000000e-09
GCST004988_11	Breast cancer	8.000000e-13

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases expression, affects expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2IG	HAP1 RANBP9 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms