RGPD3

Summary

RGPD3 (RANBP2 like and GRIP domain containing 3, HGNC:32416) is a protein-coding gene on chromosome 2q12.2, encoding RanBP2-like and GRIP domain-containing protein 3 (A6NKT7).

This gene is located in a cluster of Ran-binding protein related genes on chromosome 2 which arose through duplication in primates. The encoded protein contains an N-terminal TPR (tetratricopeptide repeat) domain, two Ran-binding domains, and a C-terminal GRIP domain (golgin-97, RanBP2alpha, Imh1p and p230/golgin-245) domain.

Source: NCBI Gene 653489 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 401 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_001144013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32416
Approved symbol	RGPD3
Name	RANBP2 like and GRIP domain containing 3
Location	2q12.2
Locus type	gene with protein product
Status	Approved
Aliases	RGP3
Ensembl gene	ENSG00000153165
Ensembl biotype	protein_coding
OMIM	612706
Entrez	653489

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000304514, ENST00000409886

RefSeq mRNA: 1 — MANE Select: NM_001144013 NM_001144013

CCDS: CCDS46379

Canonical transcript exons

ENST00000409886 — 23 exons

Exon	Start	End
ENSE00001886622	106403406	106405229
ENSE00001907451	106468217	106468413
ENSE00002477818	106459265	106459332
ENSE00002481904	106436123	106436246
ENSE00002487045	106433106	106433285
ENSE00002500452	106436414	106436589
ENSE00002512233	106452205	106452350
ENSE00002516276	106435041	106435202
ENSE00002518301	106432935	106433018
ENSE00003243383	106434637	106434774
ENSE00003286362	106434228	106434374
ENSE00003295234	106438968	106439177
ENSE00003306900	106452696	106452926
ENSE00003318454	106441293	106441380
ENSE00003323773	106413084	106413285
ENSE00003334853	106456971	106457123
ENSE00003347978	106436673	106436854
ENSE00003352012	106425994	106426088
ENSE00003380162	106429646	106429781
ENSE00003431604	106423043	106425266
ENSE00003437577	106447418	106447613
ENSE00003441781	106457567	106457678
ENSE00003453419	106415850	106415989

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 83.32.

Top tissues by expression

132 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	83.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.20	silver quality
calcaneal tendon	UBERON:0003701	73.38	gold quality
testis	UBERON:0000473	70.97	gold quality
right testis	UBERON:0004534	70.09	gold quality
left testis	UBERON:0004533	69.84	gold quality
right lobe of liver	UBERON:0001114	68.76	gold quality
liver	UBERON:0002107	64.17	gold quality
ventricular zone	UBERON:0003053	55.87	gold quality
primary visual cortex	UBERON:0002436	55.82	gold quality
cortical plate	UBERON:0005343	55.53	gold quality
islet of Langerhans	UBERON:0000006	54.69	gold quality
stromal cell of endometrium	CL:0002255	54.12	silver quality
mucosa of stomach	UBERON:0001199	53.85	gold quality
substantia nigra	UBERON:0002038	51.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	51.71	gold quality
putamen	UBERON:0001874	51.37	gold quality
prefrontal cortex	UBERON:0000451	51.15	gold quality
descending thoracic aorta	UBERON:0002345	51.14	gold quality
anterior cingulate cortex	UBERON:0009835	51.07	gold quality
cerebral cortex	UBERON:0000956	51.06	gold quality
ganglionic eminence	UBERON:0004023	50.99	gold quality
superior frontal gyrus	UBERON:0002661	50.98	gold quality
pituitary gland	UBERON:0000007	50.93	gold quality
frontal cortex	UBERON:0001870	50.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	50.80	gold quality
pancreas	UBERON:0001264	50.62	gold quality
skeletal muscle tissue	UBERON:0001134	50.35	silver quality
muscle tissue	UBERON:0002385	50.32	gold quality
hypothalamus	UBERON:0001898	50.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.72
E-MTAB-6142	no	9.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting RGPD3, 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-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-LET-7C-3P	99.95	73.42	2862
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-4727-3P	96.75	64.97	415
HSA-MIR-4714-3P	96.53	67.44	452
HSA-MIR-5579-5P	96.32	68.54	730
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-10A-3P	93.57	64.43	451

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), RANBP2 (ENSG00000153201), RANBP3L (ENSG00000164188), RGPD8 (ENSG00000169629), RGPD6 (ENSG00000183054), RGPD2 (ENSG00000185304), RGPD1 (ENSG00000187627), RGPD4 (ENSG00000196862)

Protein

Protein identifiers

RanBP2-like and GRIP domain-containing protein 3 — A6NKT7 (reviewed: A6NKT7)

All UniProt accessions (2): A6NKT7, J3KNE0

UniProt curated annotations — full annotation on UniProt →

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

RefSeq proteins (1): NP_001137485* (*=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, PF13181, PF16704

UniProt features (18 total): compositionally biased region 5, region of interest 4, domain 3, repeat 2, coiled-coil region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKT7-F1	67.49	0.30

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): 21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, chr2q12, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NLS_BEARING_PROTEIN_IMPORT_INTO_NUCLEUS, GOBP_NUCLEAR_EXPORT, GOBP_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOCC_NUCLEAR_ENVELOPE, GOCC_NUCLEAR_PORE, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_SUMO_TRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOCC_ORGANELLE_ENVELOPE, GOBP_INTRACELLULAR_TRANSPORT

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

1428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGPD3	GRIP1	Q9Y3R0	670
RGPD3	A0A3B3IRQ3	A0A3B3IRQ3	510
RGPD3	SLC35G6	P0C7Q6	434
RGPD3	KRTAP4-8	Q9BYQ9	432
RGPD3	POTEM	A6NI47	423
RGPD3	ZNF681	Q96N22	418
RGPD3	POTEC	B2RU33	384
RGPD3	VCF2	Q5XKR9	376
RGPD3	KRTAP4-3	Q9BYR4	373
RGPD3	DTD2	Q96FN9	359
RGPD3	GCC2	Q8IWJ2	350
RGPD3	KRTAP1-5	Q9BYS1	349
RGPD3	KRTAP5-11	Q6L8G4	348
RGPD3	KRTAP5-5	Q701N2	348
RGPD3	ANAPC1	Q9H1A4	336

IntAct

28 interactions, top by confidence:

A	B	Type	Score
MIA2	RGPD3	psi-mi:“MI:0914”(association)	0.530
AKIRIN2	RGPD3	psi-mi:“MI:0914”(association)	0.530
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
RCC1	RGPD3	psi-mi:“MI:0914”(association)	0.350
ESRP1	RGPD3	psi-mi:“MI:0914”(association)	0.350
CLIP1	RGPD3	psi-mi:“MI:0914”(association)	0.350
RANBP1	RGPD3	psi-mi:“MI:0914”(association)	0.350
XPO1	RGPD3	psi-mi:“MI:0914”(association)	0.350
FGFR1OP2	RGPD3	psi-mi:“MI:0914”(association)	0.350
TSNAX	RGPD3	psi-mi:“MI:0914”(association)	0.350
RGPD1	RGPD3	psi-mi:“MI:0914”(association)	0.350
NUP62	RGPD3	psi-mi:“MI:0914”(association)	0.350
HES6	RGPD3	psi-mi:“MI:0914”(association)	0.350
B9D2	RGPD3	psi-mi:“MI:2364”(proximity)	0.270
CEP152	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
CEP63	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
CEP44	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
SAMD4A	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
DISC1	RGPD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Proximity Label-MS), RGPD3 (Proximity Label-MS), RGPD3 (Proximity Label-MS), RGPD3 (Proximity Label-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (Affinity Capture-MS), RGPD3 (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, A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, D4AY02, F5H284, O00060, O49886, O93826, P0C1H7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
Mitotic Prometaphase	5	20.4×	3e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — HCC, LUSC, MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	364
Likely benign	28
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3041 predictions. Top by Δscore:

Variant	Effect	Δscore
2:106413071:T:A	donor_gain	1.0000
2:106413289:G:GC	acceptor_gain	1.0000
2:106413292:T:C	acceptor_gain	1.0000
2:106413292:T:TC	acceptor_gain	1.0000
2:106425265:CC:C	acceptor_gain	1.0000
2:106425266:CC:C	acceptor_gain	1.0000
2:106425983:T:TA	donor_gain	1.0000
2:106426089:C:CC	acceptor_gain	1.0000
2:106428263:T:TC	acceptor_gain	1.0000
2:106429643:CAC:C	donor_loss	1.0000
2:106429645:CCTGT:C	donor_loss	1.0000
2:106429778:CTTC:C	acceptor_gain	1.0000
2:106429781:CC:C	acceptor_loss	1.0000
2:106429781:CCTAT:C	acceptor_gain	1.0000
2:106429782:C:CC	acceptor_gain	1.0000
2:106429783:T:A	acceptor_loss	1.0000
2:106429785:T:TC	acceptor_gain	1.0000
2:106431491:TAG:T	donor_gain	1.0000
2:106432930:CTTA:C	donor_loss	1.0000
2:106432931:TTA:T	donor_loss	1.0000
2:106432932:TA:T	donor_loss	1.0000
2:106432933:A:AC	donor_gain	1.0000
2:106432933:AC:A	donor_gain	1.0000
2:106432934:C:CT	donor_gain	1.0000
2:106432934:CC:C	donor_gain	1.0000
2:106432934:CCTT:C	donor_gain	1.0000
2:106432934:CCTTA:C	donor_gain	1.0000
2:106433014:GAATA:G	acceptor_gain	1.0000
2:106433015:AATA:A	acceptor_gain	1.0000
2:106433016:ATA:A	acceptor_gain	1.0000

AlphaMissense

11568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:106424384:C:G	A1195P	0.994
2:106436214:A:T	V556D	0.994
2:106436454:A:G	W532R	0.994
2:106436454:A:T	W532R	0.994
2:106436677:A:G	L485P	0.994
2:106436189:T:A	R564S	0.993
2:106436189:T:G	R564S	0.993
2:106436451:A:G	W533R	0.993
2:106436451:A:T	W533R	0.993
2:106436680:T:G	D484A	0.993
2:106436681:C:G	D484H	0.993
2:106436692:A:T	I480K	0.993
2:106436813:A:G	W440R	0.993
2:106436813:A:T	W440R	0.993
2:106436146:A:G	W579R	0.992
2:106436146:A:T	W579R	0.992
2:106435152:A:C	S603R	0.991
2:106435152:A:T	S603R	0.991
2:106435154:T:G	S603R	0.991
2:106435155:T:A	R602S	0.991
2:106435155:T:G	R602S	0.991
2:106436680:T:A	D484V	0.991
2:106436680:T:C	D484G	0.991
2:106424514:A:C	F1151L	0.990
2:106424514:A:T	F1151L	0.990
2:106424516:A:G	F1151L	0.990
2:106436758:A:G	L458P	0.990
2:106441300:G:C	S353R	0.990
2:106441300:G:T	S353R	0.990
2:106441302:T:G	S353R	0.990

dbSNP variants (sampled 300 via entrez): RS1000067887 (2:106437530 GA>G), RS1000135126 (2:106449620 G>A), RS1000165143 (2:106404492 T>C), RS1000176027 (2:106414266 G>T), RS1000285554 (2:106413697 G>A), RS1000298913 (2:106449149 A>G), RS1000419740 (2:106470480 C>T), RS1000435597 (2:106408680 ATT>A,AT,ATTT), RS1000488209 (2:106408910 T>C), RS1000629835 (2:106412935 C>G,T), RS1000686139 (2:106469763 C>T), RS1000693554 (2:106413931 C>A,T), RS1000772207 (2:106406251 T>C), RS1000823556 (2:106469563 C>A,T), RS1000825175 (2:106406815 C>A,G,T)

Disease associations

OMIM: gene MIM:612706 | 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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	affects phosphorylation	1
indeno(1,2,3-cd)pyrene	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases phosphorylation	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin M1	decreases expression	1

Clinical trials (associated diseases)

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