RGPD6

Summary

RGPD6 (RANBP2 like and GRIP domain containing 6, HGNC:32419) is a protein-coding gene on chromosome 2q13, encoding RANBP2-like and GRIP domain-containing protein 5/6 (Q99666).

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 729540 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 8 total — 1 pathogenic
• MANE Select transcript: NM_001123363

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32419
Approved symbol	RGPD6
Name	RANBP2 like and GRIP domain containing 6
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	RGP6
Ensembl gene	ENSG00000183054
Ensembl biotype	protein_coding
OMIM	612709
Entrez	729540

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000329516, ENST00000330331, ENST00000437167, ENST00000446930, ENST00000455695, ENST00000459645, ENST00000463822, ENST00000473101, ENST00000480894, ENST00000484024, ENST00000490990, ENST00000696446, ENST00000696447, ENST00000696448, ENST00000696449, ENST00000918435, ENST00000918436, ENST00000918437

RefSeq mRNA: 11 — MANE Select: NM_001123363 NM_001037866, NM_001123363, NM_001384362, NM_001384363, NM_001384364, NM_001386141, NM_001386145, NM_001386155, NM_001386159, NM_001386163, NM_001387273

CCDS: CCDS42729, CCDS46388, CCDS92839

Canonical transcript exons

ENST00000329516 — 23 exons

Exon	Start	End
ENSE00001841896	110513802	110515645
ENSE00002433203	110562612	110562757
ENSE00002476264	110546554	110546677
ENSE00003290606	110563103	110563333
ENSE00003291923	110526265	110526404
ENSE00003342881	110533465	110535688
ENSE00003366160	110549393	110549602
ENSE00003527549	110543359	110543442
ENSE00003539428	110567964	110568075
ENSE00003541147	110540055	110540190
ENSE00003555183	110547104	110547285
ENSE00003555423	110551724	110551811
ENSE00003580225	110557852	110558047
ENSE00003594131	110545473	110545631
ENSE00003610939	110546845	110547020
ENSE00003613527	110545069	110545206
ENSE00003619466	110536416	110536510
ENSE00003629072	110523496	110523697
ENSE00003629196	110567376	110567528
ENSE00003660703	110569657	110569724
ENSE00003667059	110543536	110543715
ENSE00003678744	110544660	110544806
ENSE00003914027	110576953	110577222

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.26.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6726 / max 30.8240, expressed in 295 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21927	0.6726	295

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	95.26	gold quality
right testis	UBERON:0004534	95.15	gold quality
left testis	UBERON:0004533	94.67	gold quality
testis	UBERON:0000473	94.57	gold quality
calcaneal tendon	UBERON:0003701	94.04	gold quality
adrenal tissue	UBERON:0018303	92.23	gold quality
superior frontal gyrus	UBERON:0002661	91.26	gold quality
body of pancreas	UBERON:0001150	91.19	gold quality
adenohypophysis	UBERON:0002196	90.36	gold quality
pancreas	UBERON:0001264	90.33	gold quality
colonic epithelium	UBERON:0000397	90.26	gold quality
pituitary gland	UBERON:0000007	90.05	gold quality
islet of Langerhans	UBERON:0000006	90.03	gold quality
primary visual cortex	UBERON:0002436	89.07	gold quality
mucosa of stomach	UBERON:0001199	88.93	gold quality
corpus callosum	UBERON:0002336	88.38	gold quality
right coronary artery	UBERON:0001625	88.15	gold quality
ascending aorta	UBERON:0001496	88.04	gold quality
skin of abdomen	UBERON:0001416	88.00	gold quality
zone of skin	UBERON:0000014	87.93	gold quality
thoracic aorta	UBERON:0001515	87.91	gold quality
skin of leg	UBERON:0001511	87.83	gold quality
endometrium	UBERON:0001295	87.66	gold quality
descending thoracic aorta	UBERON:0002345	87.61	gold quality
endocervix	UBERON:0000458	87.22	gold quality
thyroid gland	UBERON:0002046	87.17	gold quality
thoracic mammary gland	UBERON:0005200	87.13	gold quality
prostate gland	UBERON:0002367	87.12	gold quality
gastrocnemius	UBERON:0001388	87.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.71
E-MTAB-7606	no	210.81
E-CURD-135	no	209.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

130 targeting RGPD6, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-12118	100.00	65.88	1270
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-3617-3P	99.98	67.86	918
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585

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), RGPD8 (ENSG00000169629), 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 (10): Q99666, A0A8Q3SII4, A0A8Q3SII5, A0A8Q3SIN4, A0A8Q3SIQ7, C9J1P2, C9JF75, H0YBN8, H7BZ48, 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 (11): NP_001032955, NP_001116835, NP_001371291, NP_001371292, NP_001371293, NP_001373070, NP_001373074, NP_001373084, NP_001373088, NP_001373092, NP_001374202 (=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: 58 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, 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, GOBP_IMPORT_INTO_NUCLEUS

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
RGPD6	GRIP1	Q9Y3R0	843
RGPD6	TNPO1	Q92973	814
RGPD6	LIMS3	P0CW19	651
RGPD6	MLLT10	P55197	623
RGPD6	MALL	Q13021	582
RGPD6	NPHP1	O15259	544
RGPD6	ANAPC1	Q9H1A4	404
RGPD6	GCC2	Q8IWJ2	398
RGPD6	GP5	P40197	395
RGPD6	ZSCAN30	Q86W11	393
RGPD6	LUZP6	Q538Z0	379
RGPD6	FAM25A	B3EWG3	372
RGPD6	FAM86C1P	Q9NVL1	371
RGPD6	SPIN2A	Q99865	370
RGPD6	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 142 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	6	38.5×	5e-06
mRNA transport	6	12.6×	1e-03
protein import into nucleus	9	10.4×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4820144	NC_000002.11:g.(110822372_110852372)_(110986372_111392372)del	Pathogenic

SpliceAI

3002 predictions. Top by Δscore:

Variant	Effect	Δscore
2:110515648:T:C	acceptor_gain	1.0000
2:110515655:G:C	acceptor_gain	1.0000
2:110515655:G:GC	acceptor_gain	1.0000
2:110523483:T:A	donor_gain	1.0000
2:110523492:CCAC:C	donor_loss	1.0000
2:110523694:GAAG:G	acceptor_gain	1.0000
2:110523704:T:C	acceptor_gain	1.0000
2:110523704:T:TC	acceptor_gain	1.0000
2:110526259:TCTCA:T	donor_loss	1.0000
2:110526260:CTCA:C	donor_loss	1.0000
2:110526261:TCA:T	donor_loss	1.0000
2:110526262:CAC:C	donor_loss	1.0000
2:110526263:A:C	donor_loss	1.0000
2:110526264:C:CT	donor_loss	1.0000
2:110535687:CC:C	acceptor_gain	1.0000
2:110535688:CC:C	acceptor_gain	1.0000
2:110536403:ATT:A	donor_gain	1.0000
2:110536405:T:TA	donor_gain	1.0000
2:110536411:GTTAC:G	donor_loss	1.0000
2:110536412:TTA:T	donor_loss	1.0000
2:110536413:TA:T	donor_loss	1.0000
2:110536414:ACCTT:A	donor_loss	1.0000
2:110536415:C:A	donor_loss	1.0000
2:110536508:CAA:C	acceptor_gain	1.0000
2:110536509:AA:A	acceptor_gain	1.0000
2:110536511:C:CC	acceptor_gain	1.0000
2:110540050:CTCA:C	donor_loss	1.0000
2:110540053:A:AG	donor_loss	1.0000
2:110540054:C:CA	donor_loss	1.0000
2:110540187:CTTT:C	acceptor_gain	1.0000

AlphaMissense

11603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:110568016:C:T	G67D	0.998
2:110568017:C:G	G67R	0.997
2:110534910:A:G	F1159S	0.996
2:110569699:G:T	A33E	0.996
2:110567420:C:G	A121P	0.995
2:110567969:A:C	Y83D	0.995
2:110569663:G:T	A45D	0.995
2:110533999:C:G	A1463P	0.994
2:110534909:G:C	F1159L	0.994
2:110534909:G:T	F1159L	0.994
2:110534911:A:G	F1159L	0.994
2:110567480:C:G	A101P	0.994
2:110568010:A:G	L69P	0.994
2:110568019:A:G	L66P	0.994
2:110547244:A:G	W440R	0.993
2:110547244:A:T	W440R	0.993
2:110563132:A:G	W203R	0.993
2:110563132:A:T	W203R	0.993
2:110567432:A:G	W117R	0.993
2:110567432:A:T	W117R	0.993
2:110567479:G:T	A101E	0.993
2:110567527:C:G	R85P	0.993
2:110567981:C:G	A79P	0.993
2:110535048:A:G	I1113T	0.992
2:110567525:A:G	S86P	0.992
2:110567980:G:T	A79D	0.992
2:110569691:A:C	Y36D	0.992
2:110534104:A:G	W1428R	0.991
2:110534104:A:T	W1428R	0.991
2:110551731:G:C	S353R	0.991

dbSNP variants (sampled 300 via entrez): RS1000031401 (2:110594341 T>C), RS1000493288 (2:110610671 C>G), RS1000913825 (2:110599236 A>C), RS1000985533 (2:110601113 C>A,T), RS1001515804 (2:110608412 A>T), RS1002109378 (2:110590659 T>C), RS1002155502 (2:110607996 G>A), RS1002797170 (2:110601873 T>C), RS1003193083 (2:110605983 G>T), RS1003831680 (2:110605672 G>C,T), RS1004475556 (2:110606778 T>C), RS1004943332 (2:110590872 A>G), RS1005384048 (2:110592106 G>A), RS1006113646 (2:110603756 C>G), RS1006560790 (2:110604349 T>C)

Disease associations

OMIM: gene MIM:612709 | disease phenotypes: MIM:256100

GenCC curated gene-disease

Mondo (1): nephronophthisis 1 (MONDO:0009728)

Orphanet (2): Nephronophthisis (Orphanet:655), Juvenile nephronophthisis (Orphanet:93592)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537699	Nephronophthisis, familial juvenile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
picene	decreases expression	1
abrine	increases expression	1
bisphenol Z	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Endosulfan	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Rifampin	decreases expression	1
Dronabinol	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	increases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies