RGPD8

Summary

RGPD8 (RANBP2 like and GRIP domain containing 8, HGNC:9849) is a protein-coding gene on chromosome 2q14.1, encoding RANBP2-like and GRIP domain-containing protein 8 (O14715).

Predicted to enable small GTPase binding activity. Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm.

Source: NCBI Gene 727851 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 200 total — 2 pathogenic
• MANE Select transcript: NM_001164463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9849
Approved symbol	RGPD8
Name	RANBP2 like and GRIP domain containing 8
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	RanBP2alpha
Ensembl gene	ENSG00000169629
Ensembl biotype	protein_coding
OMIM	602752
Entrez	727851

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000302558, ENST00000330575, ENST00000409750, ENST00000471422, ENST00000482903, ENST00000496537, ENST00000522286, ENST00000929966

RefSeq mRNA: 1 — MANE Select: NM_001164463 NM_001164463

CCDS: CCDS46394

Canonical transcript exons

ENST00000302558 — 23 exons

Exon	Start	End
ENSE00002439741	112421960	112422112
ENSE00002447820	112417193	112417338
ENSE00002457769	112378053	112378254
ENSE00002459041	112422548	112422659
ENSE00002461552	112380824	112380963
ENSE00002467742	112433382	112433645
ENSE00002480479	112401117	112401240
ENSE00002483202	112417684	112417914
ENSE00002517895	112388024	112390247
ENSE00002523283	112403966	112404175
ENSE00003533182	112424240	112424307
ENSE00003564739	112400036	112400194
ENSE00003586760	112406297	112406384
ENSE00003604039	112394618	112394753
ENSE00003610246	112390975	112391069
ENSE00003624035	112401667	112401848
ENSE00003642132	112399632	112399769
ENSE00003653293	112397922	112398005
ENSE00003664074	112412431	112412626
ENSE00003674443	112398099	112398278
ENSE00003689127	112401408	112401583
ENSE00003692916	112399223	112399369
ENSE00003894210	112368369	112370212

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 89.83.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1300 / max 26.2194, expressed in 570 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
202335	1.1300	570

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.83	gold quality
calcaneal tendon	UBERON:0003701	88.49	gold quality
sural nerve	UBERON:0015488	83.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.66	gold quality
right testis	UBERON:0004534	82.97	gold quality
testis	UBERON:0000473	82.95	gold quality
bone marrow cell	CL:0002092	82.02	gold quality
left testis	UBERON:0004533	81.95	gold quality
bone marrow	UBERON:0002371	81.55	gold quality
adrenal tissue	UBERON:0018303	80.47	gold quality
tonsil	UBERON:0002372	79.13	gold quality
ventricular zone	UBERON:0003053	78.89	gold quality
primary visual cortex	UBERON:0002436	78.52	gold quality
mucosa of stomach	UBERON:0001199	78.36	gold quality
right coronary artery	UBERON:0001625	78.29	gold quality
adenohypophysis	UBERON:0002196	77.89	gold quality
pituitary gland	UBERON:0000007	77.58	gold quality
islet of Langerhans	UBERON:0000006	77.52	gold quality
body of pancreas	UBERON:0001150	77.12	gold quality
thoracic mammary gland	UBERON:0005200	77.07	gold quality
endometrium	UBERON:0001295	77.02	gold quality
pancreas	UBERON:0001264	77.00	gold quality
superior frontal gyrus	UBERON:0002661	76.99	gold quality
cortical plate	UBERON:0005343	76.65	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.48	gold quality
thoracic aorta	UBERON:0001515	76.35	gold quality
ascending aorta	UBERON:0001496	76.32	gold quality
cerebellar cortex	UBERON:0002129	76.10	gold quality
cerebellar hemisphere	UBERON:0002245	76.07	gold quality
descending thoracic aorta	UBERON:0002345	76.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	37.80
E-ANND-3	no	3.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting RGPD8, 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-12118	100.00	65.88	1270
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
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-4500	99.99	72.72	2367
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

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	ranbp3a	ENSDARG00000008727
drosophila_melanogaster	RanBP3	FBGN0039110

Paralogs (10): RGPD5 (ENSG00000015568), RANBP3 (ENSG00000031823), RANBP1 (ENSG00000099901), RGPD3 (ENSG00000153165), RANBP2 (ENSG00000153201), RANBP3L (ENSG00000164188), RGPD6 (ENSG00000183054), RGPD2 (ENSG00000185304), RGPD1 (ENSG00000187627), RGPD4 (ENSG00000196862)

Protein

Protein identifiers

RANBP2-like and GRIP domain-containing protein 8 — O14715 (reviewed: O14715)

Alternative names: Ran-binding protein 2-like 3

All UniProt accessions (5): C9J6W1, O14715, F8W705, H0YBN8, J3KQ37

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with GTP-bound ARL1.

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

RefSeq proteins (1): NP_001157935* (*=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 (23 total): region of interest 5, compositionally biased region 5, sequence conflict 4, repeat 3, domain 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14715-F1	67.28	0.28

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: 62 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOMF_GTPASE_BINDING, GOBP_NUCLEAR_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NLS_BEARING_PROTEIN_IMPORT_INTO_NUCLEUS, GOBP_NUCLEAR_EXPORT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, chr2q14, GOCC_NUCLEAR_ENVELOPE, GOCC_NUCLEAR_PORE, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_SUMO_TRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY

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

GO Molecular Function (3): small GTPase binding (GO:0031267), 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 binding	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

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGPD8	GRIP1	Q9Y3R0	855
RGPD8	GOLGA4	Q13439	673
RGPD8	GOLGA1	Q92805	671
RGPD8	GCC1	Q96CN9	512
RGPD8	M0QZ92	M0QZ92	418
RGPD8	GCC2	Q8IWJ2	405
RGPD8	RNASE4	P34096	398
RGPD8	SYS1	Q8N2H4	315
RGPD8	RUSC1	Q9BVN2	311
RGPD8	ARFIP2	P53365	304
RGPD8	CCDC186	Q7Z3E2	304
RGPD8	RUNDC3A	Q59EK9	298
RGPD8	MON2	Q7Z3U7	287
RGPD8	ARFRP1	Q13795	269
RGPD8	GBF1	Q92538	260

IntAct

103 interactions, top by confidence:

A	B	Type	Score
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
NUP50	KPNA3	psi-mi:“MI:0914”(association)	0.780
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
NEMP1	RGPD8	psi-mi:“MI:0914”(association)	0.640
RAN	RGPD8	psi-mi:“MI:0914”(association)	0.640
B2M	NEMP1	psi-mi:“MI:0914”(association)	0.640
MIA2	RGPD8	psi-mi:“MI:0914”(association)	0.640
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
MIA2	RGPD3	psi-mi:“MI:0914”(association)	0.530
AKIRIN2	RGPD3	psi-mi:“MI:0914”(association)	0.530
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
IER2	KPNA3	psi-mi:“MI:0914”(association)	0.530
MLLT6	RGPD8	psi-mi:“MI:0914”(association)	0.530
TSKS	RGPD8	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530

BioGRID (105): RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS)

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 100 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
Nuclear import of Rev protein	10	63.4×	7e-14
Rev-mediated nuclear export of HIV RNA	10	59.9×	7e-14
NEP/NS2 Interacts with the Cellular Export Machinery	9	58.8×	1e-12
NS1 Mediated Effects on Host Pathways	10	53.9×	2e-13
Transport of Ribonucleoproteins into the Host Nucleus	8	53.9×	7e-11
IPs transport between nucleus and cytosol	7	50.3×	2e-09
IP3 and IP4 transport between cytosol and nucleus	7	50.3×	2e-09
IP6 and IP7 transport between cytosol and nucleus	7	50.3×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	5	47.2×	9e-06
nucleocytoplasmic transport	7	32.3×	4e-07
protein import into nucleus	12	20.3×	3e-10
mRNA transport	6	18.6×	1e-04
mRNA export from nucleus	5	17.4×	8e-04
exocytosis	6	10.7×	1e-03
chromosome segregation	5	10.2×	6e-03
cell division	9	4.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	178
Likely benign	16
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1807763	GRCh37/hg19 2q13(chr2:111369264-113142794)x1	Pathogenic
2580318	GRCh37/hg19 2q13(chr2:111335152-113127204)x1	Pathogenic

SpliceAI

3151 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112370222:G:GC	acceptor_gain	1.0000
2:112378040:T:A	donor_gain	1.0000
2:112378049:CCA:C	donor_loss	1.0000
2:112378050:CA:C	donor_loss	1.0000
2:112378258:G:GC	acceptor_gain	1.0000
2:112378261:T:C	acceptor_gain	1.0000
2:112378261:T:TC	acceptor_gain	1.0000
2:112380818:TCTCA:T	donor_loss	1.0000
2:112380819:CTCA:C	donor_loss	1.0000
2:112380820:TCA:T	donor_loss	1.0000
2:112380821:CA:C	donor_loss	1.0000
2:112380823:CC:C	donor_loss	1.0000
2:112390962:ATT:A	donor_gain	1.0000
2:112390964:T:TA	donor_gain	1.0000
2:112391070:C:CC	acceptor_gain	1.0000
2:112394613:CTCA:C	donor_loss	1.0000
2:112394614:TCA:T	donor_loss	1.0000
2:112394615:CAC:C	donor_loss	1.0000
2:112394616:A:AT	donor_loss	1.0000
2:112394617:C:A	donor_loss	1.0000
2:112394750:CTTT:C	acceptor_gain	1.0000
2:112394754:C:CC	acceptor_gain	1.0000
2:112394757:T:TC	acceptor_gain	1.0000
2:112397917:CTTA:C	donor_loss	1.0000
2:112397918:TTA:T	donor_loss	1.0000
2:112397919:TA:T	donor_loss	1.0000
2:112397920:A:AC	donor_gain	1.0000
2:112397920:AC:A	donor_gain	1.0000
2:112397921:C:CA	donor_gain	1.0000
2:112397921:CC:C	donor_gain	1.0000

AlphaMissense

11594 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112422600:C:T	G67D	0.998
2:112422601:C:G	G67R	0.998
2:112388663:A:G	W1428R	0.997
2:112388663:A:T	W1428R	0.997
2:112389554:A:G	W1131R	0.996
2:112389554:A:T	W1131R	0.996
2:112424246:G:T	A45D	0.996
2:112424282:G:T	A33E	0.996
2:112389469:A:G	F1159S	0.995
2:112389495:A:C	F1150L	0.995
2:112389495:A:T	F1150L	0.995
2:112389496:A:G	F1150S	0.995
2:112389497:A:G	F1150L	0.995
2:112422004:C:G	A121P	0.995
2:112422063:G:T	A101E	0.995
2:112422064:C:G	A101P	0.995
2:112422553:A:C	Y83D	0.995
2:112422565:C:G	A79P	0.995
2:112422603:A:G	L66P	0.995
2:112389468:G:C	F1159L	0.994
2:112389468:G:T	F1159L	0.994
2:112389470:A:G	F1159L	0.994
2:112422564:G:T	A79D	0.994
2:112422594:A:G	L69P	0.994
2:112388558:C:G	A1463P	0.993
2:112388611:A:T	V1445D	0.993
2:112389552:C:A	W1131C	0.993
2:112389552:C:G	W1131C	0.993
2:112401807:A:G	W440R	0.993
2:112401807:A:T	W440R	0.993

dbSNP variants (sampled 300 via entrez): RS1000043652 (2:112430520 C>A), RS1000097726 (2:112380412 G>A), RS1000138102 (2:112430789 C>A,T), RS1000203792 (2:112413703 T>C), RS1000382912 (2:112369895 T>C), RS1000503754 (2:112422716 C>G,T), RS1000598025 (2:112423952 G>A,C), RS1000705052 (2:112373638 C>T), RS1000717430 (2:112414777 T>C,G), RS1001116073 (2:112375057 T>C), RS1001608630 (2:112392788 A>C), RS1002337606 (2:112434418 G>A), RS1002384576 (2:112429289 C>A,T), RS1002482588 (2:112429618 C>T), RS1002734103 (2:112434261 CG>C)

Disease associations

OMIM: gene MIM:602752 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): 2q13 microdeletion syndrome (MONDO:0975887)

Orphanet (1): 2q13 microdeletion syndrome (Orphanet:684742)

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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Selenium	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	affects cotreatment, decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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