RANBP3L

Summary

RANBP3L (RAN binding protein 3 like, HGNC:26353) is a protein-coding gene on chromosome 5p13.2, encoding Ran-binding protein 3-like (Q86VV4). Nuclear export factor for BMP-specific SMAD1/5/8 that plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation by blocking osteoblast differentiation to promote myogenic differention.

Enables SMAD binding activity. Predicted to be involved in several processes, including mesenchymal cell differentiation involved in bone development; negative regulation of osteoblast differentiation; and protein export from nucleus. Predicted to be located in cytoplasm and nucleus.

Source: NCBI Gene 202151 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_145000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26353
Approved symbol	RANBP3L
Name	RAN binding protein 3 like
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25422
Ensembl gene	ENSG00000164188
Ensembl biotype	protein_coding
OMIM	616391
Entrez	202151

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000296604, ENST00000502994, ENST00000505865, ENST00000515759, ENST00000900326, ENST00000900327, ENST00000944868, ENST00000944869, ENST00000944870

RefSeq mRNA: 10 — MANE Select: NM_145000 NM_001161429, NM_001323273, NM_001323274, NM_001323275, NM_001323276, NM_001323277, NM_001323278, NM_001323279, NM_001323280, NM_145000

CCDS: CCDS3918, CCDS54843

Canonical transcript exons

ENST00000296604 — 14 exons

Exon	Start	End
ENSE00001082249	36261939	36262042
ENSE00001082250	36269951	36269990
ENSE00001082251	36257454	36257556
ENSE00001082252	36264959	36265098
ENSE00001082253	36271253	36271311
ENSE00001082254	36265449	36265520
ENSE00001082255	36301326	36301902
ENSE00001082256	36260780	36260864
ENSE00001082257	36269390	36269467
ENSE00001082258	36256941	36257071
ENSE00001337531	36251313	36251499
ENSE00001337535	36253647	36253789
ENSE00001337538	36255470	36255590
ENSE00001337651	36246913	36249697

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 87.27.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0707 / max 588.4982, expressed in 328 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61323	3.5332	304
61324	0.4613	159
61325	0.0761	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	87.27	gold quality
caudate nucleus	UBERON:0001873	86.33	gold quality
amygdala	UBERON:0001876	85.87	gold quality
putamen	UBERON:0001874	85.39	gold quality
nucleus accumbens	UBERON:0001882	85.04	gold quality
anterior cingulate cortex	UBERON:0009835	84.76	gold quality
right frontal lobe	UBERON:0002810	84.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.66	gold quality
left coronary artery	UBERON:0001626	80.19	gold quality
popliteal artery	UBERON:0002250	80.06	gold quality
tibial artery	UBERON:0007610	80.01	gold quality
prefrontal cortex	UBERON:0000451	79.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.61	gold quality
coronary artery	UBERON:0001621	77.85	gold quality
right coronary artery	UBERON:0001625	77.76	gold quality
neocortex	UBERON:0001950	77.67	gold quality
frontal cortex	UBERON:0001870	77.64	gold quality
aorta	UBERON:0000947	77.21	gold quality
forebrain	UBERON:0001890	76.49	gold quality
hypothalamus	UBERON:0001898	76.34	gold quality
descending thoracic aorta	UBERON:0002345	76.32	gold quality
temporal lobe	UBERON:0001871	75.84	gold quality
Ammon’s horn	UBERON:0001954	75.82	gold quality
cerebral cortex	UBERON:0000956	75.69	gold quality
calcaneal tendon	UBERON:0003701	75.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.29	gold quality
thoracic aorta	UBERON:0001515	73.91	gold quality
adult mammalian kidney	UBERON:0000082	73.68	gold quality
right lung	UBERON:0002167	73.62	gold quality
ascending aorta	UBERON:0001496	73.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	74.50
E-CURD-119	yes	45.49
E-GEOD-84465	yes	13.05
E-ANND-3	yes	4.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

138 targeting RANBP3L, 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-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-539-5P	99.93	70.30	2855
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

Literature-anchored findings (GeneRIF, showing 4)

• Results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation. (PMID:25755279)
• The single nucleotide polymorphism, rs16902947 in RANBP3L at 5p13.2 (p = .01), is significantly associated with Benign Prostate Hyperplasia. Rs16902947 in RANBP3L at 5p13.2 (p = .0388) is associated withalpha-adrenergic receptor antagonist drug effect in Benign Prostate Hyperplasia. (PMID:28787260)
• Loss of RANBP3L leads to transformation of renal epithelial cells towards a renal clear cell carcinoma like phenotype. (PMID:34233711)
• Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer’s disease. (PMID:38942763)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ranbp3l	ENSMUSG00000048424
rattus_norvegicus	Ranbp3l	ENSRNOG00000052173

Paralogs (10): RGPD5 (ENSG00000015568), RANBP3 (ENSG00000031823), RANBP1 (ENSG00000099901), RGPD3 (ENSG00000153165), RANBP2 (ENSG00000153201), RGPD8 (ENSG00000169629), RGPD6 (ENSG00000183054), RGPD2 (ENSG00000185304), RGPD1 (ENSG00000187627), RGPD4 (ENSG00000196862)

Protein

Protein identifiers

Ran-binding protein 3-like — Q86VV4 (reviewed: Q86VV4)

All UniProt accessions (2): D6RCM9, Q86VV4

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear export factor for BMP-specific SMAD1/5/8 that plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation by blocking osteoblast differentiation to promote myogenic differention. Directly recognizes dephosphorylated SMAD1/5/8 and mediates their nuclear export in a Ran-dependent manner.

Subunit / interactions. Interacts with SMAD1, SMAD5 and SMAD8; the interaction (with SMAD at least) increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export.

Subcellular location. Nucleus. Cytoplasm.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86VV4-1	1	yes
Q86VV4-2	2
Q86VV4-3	3

RefSeq proteins (10): NP_001154901, NP_001310202, NP_001310203, NP_001310204, NP_001310205, NP_001310206, NP_001310207, NP_001310208, NP_001310209, NP_659437* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00638

UniProt features (9 total): splice variant 3, sequence variant 3, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VV4-F1	61.71	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NUCLEAR_TRANSPORT, GOBP_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_BONE_DEVELOPMENT, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_MYOBLAST_DIFFERENTIATION, GOBP_OSSIFICATION, GOBP_REGULATION_OF_OSTEOBLAST_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_MESENCHYME_DEVELOPMENT

GO Biological Process (5): protein export from nucleus (GO:0006611), positive regulation of myoblast differentiation (GO:0045663), negative regulation of osteoblast differentiation (GO:0045668), mesenchymal cell differentiation involved in bone development (GO:1901706), intracellular transport (GO:0046907)

GO Molecular Function (2): SMAD binding (GO:0046332), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
intracellular protein transport	1
nuclear export	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
mesenchymal cell differentiation	1
bone development	1
transport	1
cellular localization	1
establishment of localization in cell	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RANBP3L	KRTAP17-1	Q9BYP8	501
RANBP3L	KIAA1755	Q5JYT7	474
RANBP3L	LMBRD2	Q68DH5	472
RANBP3L	SMAD9	O15198	462
RANBP3L	PTPRN2	Q92932	458
RANBP3L	ZNF608	Q9ULD9	457
RANBP3L	SMAD5	Q99717	454
RANBP3L	KATNAL2	Q8IYT4	426
RANBP3L	WDR70	Q9NW82	418
RANBP3L	PRSS35	Q8N3Z0	396
RANBP3L	CYP4Z1	Q86W10	395
RANBP3L	NADK2	Q4G0N4	395
RANBP3L	WT1	P19544	388
RANBP3L	FIBIN	Q8TAL6	387
RANBP3L	SLC6A12	P48065	379

IntAct

22 interactions, top by confidence:

A	B	Type	Score
MTUS2	RANBP3L	psi-mi:“MI:0915”(physical association)	0.560
KIF24	RANBP3L	psi-mi:“MI:0915”(physical association)	0.560
RANBP3L	MID2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	RANBP3L	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	RANBP3L	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	RANBP3L	psi-mi:“MI:0915”(physical association)	0.560
RANBP3L	SPRTN	psi-mi:“MI:0915”(physical association)	0.400
BIN1	RANBP3L	psi-mi:“MI:0915”(physical association)	0.000
RANBP3L	MTUS2	psi-mi:“MI:0915”(physical association)	0.000
RANBP3L	KIF24	psi-mi:“MI:0915”(physical association)	0.000
RANBP3L	MID2	psi-mi:“MI:0915”(physical association)	0.000
RANBP3L	GOLGA2	psi-mi:“MI:0915”(physical association)	0.000
RANBP3L	GOLGA6L9	psi-mi:“MI:0915”(physical association)	0.000
RANBP3L	TRIP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): RANBP3L (Co-fractionation), SPRTN (Affinity Capture-MS), RANBP3L (Affinity Capture-MS), RANBP3L (Two-hybrid), RANBP3L (Two-hybrid), RANBP3L (Two-hybrid), GOLGA2 (Two-hybrid), KIF24 (Two-hybrid), GOLGA6L9 (Two-hybrid), SPRTN (Affinity Capture-MS), RANBP3L (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JM98, A1L1H3, A7MBJ2, B2GUN4, B4F7C4, D2H3M0, D3ZF42, E1BP74, E1BPH3, E1BZ85, E1C3S7, E2QTD3, E2RDV1, O35618, O88850, P61590, P61591, P61592, P61593, P61594, Q1L981, Q501R9, Q5BLK4, Q5IFK1, Q5M7P8, Q5RC94, Q5SXH7, Q5VCS6, Q5VXU9, Q5VYS8, Q5XIN1, Q5XX13, Q68D51, Q6GPJ8, Q7TT79, Q7ZYI3, Q86VV4, Q8BJ34, Q8BUH8, Q8C0V1

Diamond homologs: G0S8I1, H2QII6, O14715, P0DJD0, P40517, P48820, P49792, Q09146, Q54KD9, Q7Z3J3, Q86VV4, Q99666, Q9ERU9, A0A0B4K7J2, A6NKT7, P0DJD1, P32499, P41920, P92985, Q09717, Q4R4T9, Q5R4Y2, Q8RWG8, Q9C829, Q9CT10, Q9H6Z4, Q9LMK7, Q9LW88, Q6PDH4, Q9USL4, G0SDP9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1759 predictions. Top by Δscore:

Variant	Effect	Δscore
5:36251495:CTGGC:C	acceptor_gain	1.0000
5:36251496:TGGC:T	acceptor_gain	1.0000
5:36251497:GGC:G	acceptor_gain	1.0000
5:36251498:GC:G	acceptor_gain	1.0000
5:36251499:CC:C	acceptor_gain	1.0000
5:36251500:C:A	acceptor_loss	1.0000
5:36251500:C:CC	acceptor_gain	1.0000
5:36251501:T:C	acceptor_loss	1.0000
5:36251503:C:CT	acceptor_gain	1.0000
5:36251504:A:C	acceptor_gain	1.0000
5:36251512:C:CT	acceptor_gain	1.0000
5:36251513:A:C	acceptor_gain	1.0000
5:36253787:TAA:T	acceptor_gain	1.0000
5:36253790:C:CC	acceptor_gain	1.0000
5:36255468:A:AC	donor_gain	1.0000
5:36255469:C:CC	donor_gain	1.0000
5:36257448:TCTTA:T	donor_loss	1.0000
5:36257449:CTTAC:C	donor_loss	1.0000
5:36257450:TTA:T	donor_loss	1.0000
5:36257451:TAC:T	donor_loss	1.0000
5:36257452:A:AC	donor_gain	1.0000
5:36257453:C:CC	donor_gain	1.0000
5:36257455:TGA:T	donor_gain	1.0000
5:36257555:CC:C	acceptor_gain	1.0000
5:36257556:CC:C	acceptor_gain	1.0000
5:36257556:CCTG:C	acceptor_loss	1.0000
5:36257558:T:A	acceptor_loss	1.0000
5:36258148:A:C	donor_gain	1.0000
5:36259746:T:A	donor_gain	1.0000
5:36260862:CAT:C	acceptor_gain	1.0000

AlphaMissense

3069 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:36255517:A:G	L326P	0.994
5:36255548:A:G	W316R	0.994
5:36255548:A:T	W316R	0.994
5:36253691:C:G	A375P	0.990
5:36253749:G:C	S355R	0.990
5:36253749:G:T	S355R	0.990
5:36253751:T:G	S355R	0.990
5:36251454:G:T	R405S	0.989
5:36255472:A:G	L341P	0.989
5:36253783:C:G	R344P	0.988
5:36251453:C:G	R405P	0.987
5:36253784:G:T	R344S	0.987
5:36255523:A:G	L324S	0.987
5:36255474:T:A	R340S	0.986
5:36255474:T:G	R340S	0.986
5:36255582:G:C	C304W	0.986
5:36253690:G:T	A375D	0.985
5:36253756:A:G	L353P	0.982
5:36255584:A:G	C304R	0.982
5:36260807:A:C	F214L	0.982
5:36260807:A:T	F214L	0.982
5:36260809:A:G	F214L	0.982
5:36253656:A:C	F386L	0.981
5:36253656:A:T	F386L	0.981
5:36253658:A:G	F386L	0.981
5:36255476:T:C	R340G	0.981
5:36255517:A:T	L326Q	0.980
5:36255475:C:G	R340T	0.979
5:36255513:A:C	N327K	0.978
5:36255513:A:T	N327K	0.978

dbSNP variants (sampled 300 via entrez): RS1000094941 (5:36285155 G>C), RS1000130597 (5:36278903 G>A), RS1000141371 (5:36260078 A>G), RS1000172021 (5:36260428 A>G), RS1000275344 (5:36299304 C>T), RS1000317218 (5:36291588 C>T), RS1000435897 (5:36271813 T>G), RS1000480116 (5:36291168 T>C,G), RS1000536570 (5:36301986 G>A), RS1000548724 (5:36284793 A>G), RS1000581254 (5:36285017 G>A), RS1000689167 (5:36296147 A>G), RS1000717377 (5:36278025 A>G), RS1000732838 (5:36277477 T>A), RS1000761054 (5:36295964 A>G)

Disease associations

OMIM: gene MIM:616391 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001744_1	Serum tamsulosin hydrochloride concentration	1.000000e-07
GCST003542_17	Night sleep phenotypes	4.000000e-06
GCST003542_3	Night sleep phenotypes	1.000000e-06
GCST005580_269	Intraocular pressure	5.000000e-10
GCST005580_298	Intraocular pressure	3.000000e-09
GCST007014_4	Lumbar spine bone mineral density (trabecular)	2.000000e-08
GCST007015_13	Lumbar spine bone mineral density (integral)	3.000000e-07
GCST010118_41	Type 2 diabetes	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0007620	volumetric bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Tetrachlorodibenzodioxin	affects expression, affects cotreatment, decreases expression	2
bisphenol A	decreases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	increases expression	1
Endosulfan	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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