RGPD5

Summary

RGPD5 (RANBP2 like and GRIP domain containing 5, HGNC:32418) is a protein-coding gene on chromosome 2q13, encoding RANBP2-like and GRIP domain-containing protein 5/6 (Q99666).

RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene shares a high degree of sequence identity with RANBP2, a large RAN-binding protein localized at the cytoplasmic side of the nuclear pore complex. It is believed that this RANBP2 gene family member arose from a duplication event 3 Mb distal to RANBP2. Alternative splicing has been observed for this locus and two variants are described. Additional splicing is suggested but complete sequence for further transcripts has not been determined.

Source: NCBI Gene 84220 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_005054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32418
Approved symbol	RGPD5
Name	RANBP2 like and GRIP domain containing 5
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	RGP5, BS-63, DKFZp686I1842
Ensembl gene	ENSG00000015568
Ensembl biotype	protein_coding
OMIM	612708
Entrez	84220

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000016946, ENST00000272454, ENST00000393283, ENST00000413468, ENST00000430736, ENST00000432606, ENST00000441344, ENST00000472794, ENST00000477523, ENST00000482778, ENST00000493394, ENST00000495473, ENST00000495582, ENST00000931938

RefSeq mRNA: 2 — MANE Select: NM_005054 NM_005054, NM_032260

CCDS: CCDS2082, CCDS2083

Canonical transcript exons

ENST00000016946 — 23 exons

Exon	Start	End
ENSE00001814572	109855862	109857705
ENSE00002432472	109794305	109794537
ENSE00002445929	109824830	109824953
ENSE00002466468	109808750	109808895
ENSE00003270306	109845103	109845242
ENSE00003275858	109803432	109803543
ENSE00003385170	109835819	109838042
ENSE00003430849	109808174	109808404
ENSE00003470180	109826301	109826438
ENSE00003489964	109828065	109828148
ENSE00003496718	109825876	109826034
ENSE00003517670	109847810	109848011
ENSE00003539089	109824222	109824403
ENSE00003557068	109819696	109819783
ENSE00003588845	109827792	109827971
ENSE00003589951	109821905	109822114
ENSE00003606722	109834997	109835091
ENSE00003608895	109801783	109801850
ENSE00003623998	109831317	109831452
ENSE00003642843	109813460	109813655
ENSE00003684229	109824487	109824662
ENSE00003691380	109826701	109826847
ENSE00003790096	109803979	109804131

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 97.77.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6698 / max 31.0258, expressed in 821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21928	1.6698	821
202335	1.1300	570

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.77	gold quality
buccal mucosa cell	CL:0002336	97.06	gold quality
sural nerve	UBERON:0015488	96.51	gold quality
trachea	UBERON:0003126	94.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.79	gold quality
nipple	UBERON:0002030	93.56	gold quality
pylorus	UBERON:0001166	93.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.96	gold quality
bone marrow cell	CL:0002092	92.67	gold quality
superior surface of tongue	UBERON:0007371	92.26	gold quality
adrenal tissue	UBERON:0018303	92.11	gold quality
saphenous vein	UBERON:0007318	91.88	gold quality
corpus callosum	UBERON:0002336	91.45	gold quality
trigeminal ganglion	UBERON:0001675	91.11	gold quality
renal medulla	UBERON:0000362	90.87	gold quality
cardia of stomach	UBERON:0001162	90.36	gold quality
cauda epididymis	UBERON:0004360	89.84	gold quality
caput epididymis	UBERON:0004358	89.74	gold quality
thymus	UBERON:0002370	89.08	gold quality
colonic epithelium	UBERON:0000397	88.87	gold quality
corpus epididymis	UBERON:0004359	88.57	gold quality
sperm	CL:0000019	88.29	gold quality
tendon	UBERON:0000043	88.18	gold quality
pericardium	UBERON:0002407	88.10	gold quality
gastrocnemius	UBERON:0001388	87.63	gold quality
right lobe of liver	UBERON:0001114	87.54	gold quality
pharyngeal mucosa	UBERON:0000355	87.53	gold quality
muscle of leg	UBERON:0001383	86.97	gold quality
dorsal root ganglion	UBERON:0000044	86.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.69	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	778.32
E-CURD-122	yes	17.81
E-ANND-3	yes	10.67
E-GEOD-106540	no	321.25
E-MTAB-7606	no	245.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting RGPD5, 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-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	ranbp3a	ENSDARG00000008727
drosophila_melanogaster	RanBP3	FBGN0039110

Paralogs (10): RANBP3 (ENSG00000031823), RANBP1 (ENSG00000099901), RGPD3 (ENSG00000153165), RANBP2 (ENSG00000153201), RANBP3L (ENSG00000164188), RGPD8 (ENSG00000169629), RGPD6 (ENSG00000183054), RGPD2 (ENSG00000185304), RGPD1 (ENSG00000187627), RGPD4 (ENSG00000196862)

Protein

Protein identifiers

RANBP2-like and GRIP domain-containing protein 5/6 — Q99666 (reviewed: Q99666)

Alternative names: Ran-binding protein 2-like 1/2, Sperm membrane protein BS-63

All UniProt accessions (6): Q99666, C9J1P2, C9J1W9, C9J6W1, H0YBN8, V9HWE4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in testis.

Miscellaneous. One of the 8 copies of RANBP2 clustered close to the chromosome 2 centromere.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99666-1	1	yes
Q99666-2	2

RefSeq proteins (2): NP_005045, NP_115636 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000156	Ran_bind_dom	Domain
IPR000237	GRIP_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR032023	GCC2_Rab_bind	Domain
IPR045255	RanBP1-like	Family

Pfam: PF00638, PF01465, PF16704

UniProt features (38 total): sequence conflict 16, compositionally biased region 6, region of interest 5, repeat 3, domain 3, modified residue 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99666-F1	67.02	0.27

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 (2): 19, 21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, AAGCCAT_MIR135A_MIR135B, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NLS_BEARING_PROTEIN_IMPORT_INTO_NUCLEUS, MODULE_175, GOBP_NUCLEAR_EXPORT, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, SUZUKI_RESPONSE_TO_TSA, GOCC_NUCLEAR_ENVELOPE, LIU_SOX4_TARGETS_UP, MASSARWEH_TAMOXIFEN_RESISTANCE_UP

GO Biological Process (2): NLS-bearing protein import into nucleus (GO:0006607), intracellular transport (GO:0046907)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (2): nuclear pore (GO:0005643), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein import into nucleus	1
transport	1
cellular localization	1
establishment of localization in cell	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
nuclear envelope	1
nuclear protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGPD5	GRIP1	Q9Y3R0	843
RGPD5	TNPO1	Q92973	814
RGPD5	LIMS3	P0CW19	651
RGPD5	MLLT10	P55197	623
RGPD5	MALL	Q13021	582
RGPD5	NPHP1	O15259	544
RGPD5	ANAPC1	Q9H1A4	404
RGPD5	GCC2	Q8IWJ2	398
RGPD5	GP5	P40197	395
RGPD5	ZSCAN30	Q86W11	393
RGPD5	LUZP6	Q538Z0	379
RGPD5	FAM25A	B3EWG3	372
RGPD5	FAM86C1P	Q9NVL1	371
RGPD5	SPIN2A	Q99865	370
RGPD5	ACTL7A	Q9Y615	363

IntAct

140 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
CENPS	CENPX	psi-mi:“MI:0914”(association)	0.810
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
KPNA2	NUP153	psi-mi:“MI:0914”(association)	0.790
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
RAN	RGPD5	psi-mi:“MI:0915”(physical association)	0.660
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
B2M	NEMP1	psi-mi:“MI:0914”(association)	0.640
RAN	RGPD8	psi-mi:“MI:0914”(association)	0.640
NEMP1	RANGAP1	psi-mi:“MI:0914”(association)	0.640
MIA2	RGPD8	psi-mi:“MI:0914”(association)	0.640
NUP43	NUP98	psi-mi:“MI:0914”(association)	0.640
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530

BioGRID (173): RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), RGPD5 (Co-fractionation)

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

Diamond homologs: 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, G0S8I1, Q09146, Q86VV4, A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, D4AY02, F5H284, O00060

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Rev-mediated nuclear export of HIV RNA	8	30.2×	7e-08
Postmitotic nuclear pore complex (NPC) reformation	6	29.1×	5e-06
Nuclear import of Rev protein	7	28.0×	9e-07
NEP/NS2 Interacts with the Cellular Export Machinery	6	24.7×	9e-06
NS1 Mediated Effects on Host Pathways	7	23.8×	2e-06
Transport of the SLBP independent Mature mRNA	6	23.3×	1e-05
Transport of the SLBP Dependant Mature mRNA	6	22.7×	1e-05
IPs transport between nucleus and cytosol	5	22.7×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	5	32.4×	1e-04
mRNA transport	6	12.7×	1e-03
protein import into nucleus	9	10.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2960 predictions. Top by Δscore:

Variant	Effect	Δscore
2:109794538:G:C	donor_loss	1.0000
2:109794539:T:A	donor_loss	1.0000
2:109801781:A:AG	acceptor_gain	1.0000
2:109801782:G:GA	acceptor_gain	1.0000
2:109801782:GA:G	acceptor_gain	1.0000
2:109801782:GAA:G	acceptor_gain	1.0000
2:109801782:GAAGT:G	acceptor_gain	1.0000
2:109801847:AAAAG:A	donor_loss	1.0000
2:109801848:AAA:A	donor_gain	1.0000
2:109801848:AAAG:A	donor_loss	1.0000
2:109801849:AA:A	donor_gain	1.0000
2:109801850:AG:A	donor_loss	1.0000
2:109801851:G:GG	donor_gain	1.0000
2:109801851:GTA:G	donor_loss	1.0000
2:109801852:T:TC	donor_loss	1.0000
2:109801853:A:AG	donor_loss	1.0000
2:109801854:AGTA:A	donor_loss	1.0000
2:109803424:A:G	acceptor_gain	1.0000
2:109803431:GATAC:G	acceptor_gain	1.0000
2:109803542:GG:G	donor_gain	1.0000
2:109803543:GG:G	donor_gain	1.0000
2:109803543:GGT:G	donor_loss	1.0000
2:109803544:G:T	donor_loss	1.0000
2:109803545:T:A	donor_loss	1.0000
2:109803970:T:TA	acceptor_gain	1.0000
2:109803975:T:G	acceptor_gain	1.0000
2:109803976:TAG:T	acceptor_loss	1.0000
2:109803977:A:AG	acceptor_gain	1.0000
2:109803978:G:GA	acceptor_gain	1.0000
2:109803978:GC:G	acceptor_gain	1.0000

AlphaMissense

11603 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000098584 (2:109772680 T>C), RS1000510827 (2:109780216 G>A), RS1001023292 (2:109763320 A>C), RS1001104189 (2:109779073 T>C), RS1001174302 (2:109767943 C>T), RS1001397073 (2:109758663 G>A,C), RS1001771143 (2:109767451 A>G), RS1002181661 (2:109775787 A>G), RS1002288495 (2:109761090 G>A), RS1002811511 (2:109761442 C>A,G), RS1004141235 (2:109765910 C>A,T), RS1004535730 (2:109766378 C>G), RS1004624874 (2:109759179 CAT>C), RS1004636256 (2:109758697 G>A), RS1005114996 (2:109769684 G>A)

Disease associations

OMIM: gene MIM:612708 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, increases methylation	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects expression	1
Caffeine	increases phosphorylation	1
Clorgyline	increases expression	1
Doxorubicin	increases expression	1
Formaldehyde	decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, increases expression	1
Plant Oils	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
S-Nitrosoglutathione	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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