RANBP6

Summary

RANBP6 (RAN binding protein 6, HGNC:9851) is a protein-coding gene on chromosome 9p24.1, encoding Ran-binding protein 6 (O60518). May function in nuclear protein import as nuclear transport receptor.

Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Located in mitochondrion.

Source: NCBI Gene 26953 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 140 total
• MANE Select transcript: NM_012416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9851
Approved symbol	RANBP6
Name	RAN binding protein 6
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137040
Ensembl biotype	protein_coding
Entrez	26953

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000259569, ENST00000485372, ENST00000623170

RefSeq mRNA: 3 — MANE Select: NM_012416 NM_001243202, NM_001243203, NM_012416

CCDS: CCDS6467, CCDS78378

Canonical transcript exons

ENST00000259569 — 1 exons

Exon	Start	End
ENSE00000813183	6011025	6015624

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2906 / max 401.9012, expressed in 1736 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99849	15.0946	1736
205421	0.1960	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.94	gold quality
biceps brachii	UBERON:0001507	95.59	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.34	gold quality
choroid plexus epithelium	UBERON:0003911	95.03	gold quality
substantia nigra pars compacta	UBERON:0001965	94.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.78	gold quality
heart right ventricle	UBERON:0002080	94.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.08	gold quality
pons	UBERON:0000988	94.07	gold quality
orbitofrontal cortex	UBERON:0004167	92.95	gold quality
superior vestibular nucleus	UBERON:0007227	92.86	gold quality
vastus lateralis	UBERON:0001379	92.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.65	gold quality
cerebellar vermis	UBERON:0004720	92.56	gold quality
parietal lobe	UBERON:0001872	92.38	gold quality
postcentral gyrus	UBERON:0002581	92.36	gold quality
quadriceps femoris	UBERON:0001377	91.93	gold quality
dorsal root ganglion	UBERON:0000044	91.91	gold quality
palpebral conjunctiva	UBERON:0001812	91.71	gold quality
germinal epithelium of ovary	UBERON:0001304	91.63	gold quality
eye	UBERON:0000970	91.59	gold quality
superior frontal gyrus	UBERON:0002661	91.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.41	gold quality
pigmented layer of retina	UBERON:0001782	91.25	gold quality
retina	UBERON:0000966	91.23	gold quality
medulla oblongata	UBERON:0001896	91.13	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.05	gold quality
frontal pole	UBERON:0002795	90.93	gold quality
islet of Langerhans	UBERON:0000006	90.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting RANBP6, 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-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-6510-5P	99.14	66.59	1081

Literature-anchored findings (GeneRIF, showing 1)

• Data indicate a mechanism of epidermal growth factor receptor (EGFR) regulation through the importin beta family member RAN-binding protein 6 (RanBP6). (PMID:29229958)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ranbp6	ENSMUSG00000074909
rattus_norvegicus	Ranbp6	ENSRNOG00000053859
drosophila_melanogaster	Karybeta3	FBGN0087013
caenorhabditis_elegans		WBGENE00002076
caenorhabditis_elegans	imb-3	WBGENE00002077

Paralogs (5): IPO5 (ENSG00000065150), TNPO1 (ENSG00000083312), TNPO2 (ENSG00000105576), KPNB1 (ENSG00000108424), IPO4 (ENSG00000196497)

Protein

Protein identifiers

Ran-binding protein 6 — O60518 (reviewed: O60518)

All UniProt accessions (3): A0A096LNS2, A0A096LPA6, O60518

UniProt curated annotations — full annotation on UniProt →

Function. May function in nuclear protein import as nuclear transport receptor.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the importin beta family.

RefSeq proteins (3): NP_001230131, NP_001230132, NP_036548* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000357	HEAT	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR040122	Importin_beta	Family
IPR041389	Importin_rep_6	Repeat
IPR041653	Importin_rep_4	Repeat
IPR057672	TPR_IPO4/5	Domain
IPR058584	IMB1_TNPO1-like_TPR	Domain

Pfam: PF02985, PF13513, PF18808, PF18829, PF25574, PF25780

UniProt features (13 total): repeat 7, initiator methionine 1, chain 1, coiled-coil region 1, modified residue 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60518-F1	91.28	0.74

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, OCT1_07, GARY_CD5_TARGETS_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GCM_NF2, ACEVEDO_LIVER_CANCER_UP, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, ATF_01

GO Biological Process (2): protein import into nucleus (GO:0006606), protein transport (GO:0015031)

GO Molecular Function (3): nuclear localization sequence binding (GO:0008139), nuclear import signal receptor activity (GO:0061608), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
import into nucleus	2
intracellular membrane-bounded organelle	2
intracellular protein transport	1
protein localization to nucleus	1
establishment of protein localization to organelle	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
signal sequence receptor activity	1
nucleocytoplasmic carrier activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
cell junction	1

Protein interactions and networks

STRING

2184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RANBP6	RANBP17	Q9H2T7	622
RANBP6	NUP93	Q8N1F7	617
RANBP6	XPOT	O43592	606
RANBP6	IPO13	O94829	589
RANBP6	KPNB1	Q14974	568
RANBP6	RAN	P17080	557
RANBP6	AGFG2	O95081	556
RANBP6	TNPO3	Q9Y5L0	549
RANBP6	MRPL46	Q9H2W6	546
RANBP6	IPO8	O15397	542
RANBP6	TIMM10B	Q9Y5J6	540
RANBP6	IPO11	Q9UI26	535
RANBP6	XPO1	O14980	514
RANBP6	MRPS5	P82675	514
RANBP6	CSE1L	P55060	509

IntAct

91 interactions, top by confidence:

A	B	Type	Score
ARMCX3	RANBP6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
RANBP6	MUL1	psi-mi:“MI:0914”(association)	0.640
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
NOL9	IPO5	psi-mi:“MI:0914”(association)	0.530
AVPI1	UNC119B	psi-mi:“MI:0914”(association)	0.530
CA14	EXOC5	psi-mi:“MI:0914”(association)	0.530
CCDC59	GAPDHS	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
RANBP6		psi-mi:“MI:0915”(physical association)	0.500
RANBP6	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
PB1	IPO5	psi-mi:“MI:0914”(association)	0.350
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
M2	AGPS	psi-mi:“MI:0914”(association)	0.350
PB1		psi-mi:“MI:0914”(association)	0.350
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (170): RANBP6 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), CLTC (Co-fractionation), COPB1 (Co-fractionation), MCM7 (Co-fractionation), RANBP6 (Co-fractionation), RANBP6 (Co-fractionation), RANBP6 (Co-fractionation), RANBP6 (Co-fractionation), RANBP6 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS)

ESM2 similar proteins: A5D785, A5WW24, O00410, O04375, O04376, O15397, O35638, O46563, O60518, O95373, Q08AM6, Q16401, Q499Y0, Q569Z2, Q5IFJ8, Q5R9G4, Q5R9J2, Q5ZLT0, Q5ZMR9, Q68F38, Q6GMY9, Q704U0, Q7PC79, Q7TMY7, Q802D3, Q8AY73, Q8BIV3, Q8BKC5, Q8GUL2, Q8K2V6, Q8N3U4, Q8VI75, Q8WVM7, Q91YE6, Q924C1, Q96P70, Q99NF8, Q9C0E2, Q9D3E6, Q9DGN0

Diamond homologs: O00410, O14089, O60518, O74476, P32337, Q8BIV3, Q8BKC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	134
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

44 predictions. Top by Δscore:

Variant	Effect	Δscore
9:6014467:T:TA	donor_gain	0.9100
9:6014468:C:A	donor_gain	0.6900
9:6015502:G:A	donor_gain	0.6900
9:6015469:G:T	donor_gain	0.5800
9:6015460:T:TA	donor_gain	0.5500
9:6015492:T:TA	donor_gain	0.5500
9:6015407:T:TA	donor_gain	0.5400
9:6015516:CAG:C	donor_gain	0.5400
9:6014359:G:GC	acceptor_gain	0.5200
9:6015458:AGT:A	donor_gain	0.5200
9:6014360:A:AA	acceptor_gain	0.5100
9:6014361:A:AA	acceptor_gain	0.5100
9:6014358:T:TA	acceptor_gain	0.4300
9:6015414:TCATA:T	donor_gain	0.4000
9:6014362:G:A	acceptor_gain	0.3900
9:6015241:C:CC	acceptor_gain	0.3700
9:6015240:A:AC	acceptor_gain	0.3600
9:6015468:A:T	donor_gain	0.3600
9:6015013:T:TA	donor_gain	0.3000
9:6013436:A:C	acceptor_gain	0.2800
9:6015465:C:T	donor_gain	0.2800
9:6015410:C:T	donor_gain	0.2500
9:6015427:T:TA	donor_gain	0.2400
9:6014368:G:GA	acceptor_gain	0.2300
9:6015463:TACAC:T	donor_loss	0.2300
9:6015464:ACAC:A	donor_loss	0.2300
9:6015465:CACA:C	donor_loss	0.2300
9:6015466:ACAGA:A	donor_loss	0.2300
9:6015467:C:T	donor_loss	0.2300
9:6015468:AGAC:A	donor_loss	0.2300

AlphaMissense

7312 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:6012528:A:G	L1027P	0.998
9:6012598:A:G	W1004R	0.998
9:6012598:A:T	W1004R	0.998
9:6012661:C:G	A983P	0.998
9:6012668:A:C	C980W	0.998
9:6013445:A:C	F721L	0.998
9:6013445:A:T	F721L	0.998
9:6013447:A:G	F721L	0.998
9:6013683:G:T	A642D	0.998
9:6015199:A:G	W137R	0.998
9:6015199:A:T	W137R	0.998
9:6012585:A:G	L1008P	0.997
9:6012934:C:G	G892R	0.997
9:6012934:C:T	G892R	0.997
9:6013194:A:G	L805P	0.997
9:6014443:C:G	A389P	0.997
9:6014451:C:T	G386E	0.997
9:6014460:C:G	R383P	0.997
9:6014470:A:G	W380R	0.997
9:6014470:A:T	W380R	0.997
9:6014757:C:G	R284P	0.997
9:6012660:G:T	A983E	0.996
9:6012670:A:G	C980R	0.996
9:6012801:C:T	G936D	0.996
9:6012915:T:A	D898V	0.996
9:6012915:T:G	D898A	0.996
9:6012933:C:T	G892E	0.996
9:6013348:A:G	W754R	0.996
9:6013348:A:T	W754R	0.996
9:6013395:A:G	L738P	0.996

dbSNP variants (sampled 300 via entrez): RS1000900409 (9:6015894 G>C,T), RS1001368829 (9:6015404 T>G), RS1001634296 (9:6013009 G>A,C), RS1001716726 (9:6015687 G>C,T), RS1002579898 (9:6011173 T>C), RS1002709216 (9:6017191 G>C), RS1002976053 (9:6016783 C>G,T), RS1003366132 (9:6017381 G>A), RS1004715106 (9:6015708 C>T), RS1005096531 (9:6016377 GGATA>G), RS1006338239 (9:6016975 A>C,G), RS1006390628 (9:6016819 A>G), RS1006888919 (9:6016107 C>A,T), RS1006941164 (9:6015945 T>A), RS1007217659 (9:6017147 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST002083_24	Self-reported allergy	2.000000e-09
GCST002322_21	Asthma and hay fever	2.000000e-06
GCST003987_3	Asthma	1.000000e-31
GCST003990_13	Allergy	8.000000e-11
GCST005038_118	Allergic disease (asthma, hay fever or eczema)	1.000000e-35
GCST005038_71	Allergic disease (asthma, hay fever or eczema)	3.000000e-10
GCST005212_26	Asthma	7.000000e-20
GCST005213_5	Asthma (childhood onset)	3.000000e-08
GCST006409_43	Allergic rhinitis	2.000000e-14
GCST006862_14	Asthma	4.000000e-29
GCST007013_3	Hippocampal volume in mild cognitive impairment	3.000000e-07
GCST007563_32	Allergic disease (asthma, hay fever or eczema)	4.000000e-08
GCST007797_3	Asthma onset (childhood vs adult)	4.000000e-12
GCST007797_5	Asthma onset (childhood vs adult)	1.000000e-14
GCST007797_6	Asthma onset (childhood vs adult)	9.000000e-22
GCST007797_7	Asthma onset (childhood vs adult)	1.000000e-20
GCST007798_88	Asthma	3.000000e-43
GCST007798_89	Asthma	5.000000e-41
GCST007798_90	Asthma	3.000000e-72
GCST007798_91	Asthma	9.000000e-71
GCST007799_22	Asthma (adult onset)	8.000000e-20
GCST007799_23	Asthma (adult onset)	2.000000e-29
GCST007800_41	Asthma (childhood onset)	3.000000e-62
GCST007800_46	Asthma (childhood onset)	5.000000e-115
GCST007993_10	Asthma (adult onset)	3.000000e-17
GCST007995_56	Asthma (childhood onset)	7.000000e-42
GCST008916_119	Asthma	1.000000e-15
GCST008916_20	Asthma	5.000000e-36
GCST008916_26	Asthma	3.000000e-64
GCST009798_28	Asthma	4.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004847	age at onset
EFO:1002011	adult onset asthma

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel chloride	decreases expression	1
nickel sulfate	decreases expression	1
1-nitropyrene	increases expression	1
pentanal	decreases expression	1
avobenzone	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects expression	1
Atrazine	decreases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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