RGP1

Summary

RGP1 (RGP1 partner of RAB6A GEF complex, HGNC:21965) is a protein-coding gene on chromosome 9p13.3, encoding RAB6A-GEF complex partner protein 2 (Q92546). The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP and may thereby required for efficient fusion of endosome-derived vesicles with the Golgi compartment. It is a selective cancer dependency (DepMap: 44.0% of cell lines).

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in negative regulation of protein catabolic process; positive regulation of GTPase activity; and retrograde transport, endosome to Golgi. Located in cytosol and plasma membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex.

Source: NCBI Gene 9827 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 63 total
• Cancer dependency (DepMap): dependent in 44.0% of screened cell lines
• MANE Select transcript: NM_001080496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21965
Approved symbol	RGP1
Name	RGP1 partner of RAB6A GEF complex
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000107185
Ensembl biotype	protein_coding
OMIM	615742
Entrez	9827

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000378078, ENST00000496906, ENST00000880976, ENST00000880977, ENST00000931309, ENST00000965086

RefSeq mRNA: 1 — MANE Select: NM_001080496 NM_001080496

CCDS: CCDS47964

Canonical transcript exons

ENST00000378078 — 9 exons

Exon	Start	End
ENSE00000699418	35750658	35750741
ENSE00000699421	35750840	35750989
ENSE00001476210	35749287	35749408
ENSE00001929561	35752651	35758585
ENSE00003467286	35749737	35749871
ENSE00003492519	35751627	35751754
ENSE00003529146	35751266	35751412
ENSE00003615089	35750243	35750379
ENSE00003635275	35751956	35752145

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7619 / max 79.2193, expressed in 1799 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96628	16.4018	1799
96629	0.3601	175

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.93	gold quality
medial globus pallidus	UBERON:0002477	91.81	gold quality
pylorus	UBERON:0001166	91.01	gold quality
renal medulla	UBERON:0000362	90.88	gold quality
nipple	UBERON:0002030	90.37	gold quality
globus pallidus	UBERON:0001875	89.82	gold quality
cardia of stomach	UBERON:0001162	88.63	gold quality
cervix squamous epithelium	UBERON:0006922	88.61	silver quality
body of tongue	UBERON:0011876	88.30	gold quality
saphenous vein	UBERON:0007318	87.97	gold quality
gluteal muscle	UBERON:0002000	87.20	gold quality
inferior vagus X ganglion	UBERON:0005363	86.72	gold quality
islet of Langerhans	UBERON:0000006	86.51	gold quality
vena cava	UBERON:0004087	86.46	silver quality
tongue	UBERON:0001723	86.45	gold quality
parotid gland	UBERON:0001831	86.08	gold quality
stromal cell of endometrium	CL:0002255	86.06	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.04	gold quality
superior surface of tongue	UBERON:0007371	86.04	gold quality
triceps brachii	UBERON:0001509	86.01	silver quality
gastrocnemius	UBERON:0001388	85.38	gold quality
ventral tegmental area	UBERON:0002691	85.33	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.04	gold quality
pons	UBERON:0000988	85.01	gold quality
muscle of leg	UBERON:0001383	85.01	gold quality
mucosa of transverse colon	UBERON:0004991	84.78	gold quality
pharyngeal mucosa	UBERON:0000355	84.55	gold quality
medulla oblongata	UBERON:0001896	84.22	gold quality
muscle organ	UBERON:0001630	84.05	gold quality
rectum	UBERON:0001052	83.86	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.49

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 44.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase. (PMID:23091056)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgp1	ENSDARG00000006545
mus_musculus	Rgp1	ENSMUSG00000028468
rattus_norvegicus	Rgp1	ENSRNOG00000016309
drosophila_melanogaster	CG1116	FBGN0037297
caenorhabditis_elegans		WBGENE00010815

Protein

Protein identifiers

RAB6A-GEF complex partner protein 2 — Q92546 (reviewed: Q92546)

Alternative names: Retrograde Golgi transport protein RGP1 homolog

All UniProt accessions (1): Q92546

UniProt curated annotations — full annotation on UniProt →

Function. The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP and may thereby required for efficient fusion of endosome-derived vesicles with the Golgi compartment. The RIC1-RGP1 complex participates in the recycling of mannose-6-phosphate receptors.

Subunit / interactions. Forms a complex with RIC1; the interaction enhances RAB6A GTPase activity. Interacts with RIC1. Interacts with RAB6A; the interaction is direct with a preference for RAB6A-GDP. Interacts with RAB33B.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Similarity. Belongs to the RGP1 family.

RefSeq proteins (1): NP_001073965* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014848	Rgp1	Family

Pfam: PF08737

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92546-F1	85.74	0.58

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6811438	Intra-Golgi traffic
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 119 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOCC_TRANS_GOLGI_NETWORK, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, chr9p13, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (3): retrograde transport, endosome to Golgi (GO:0042147), negative regulation of protein catabolic process (GO:0042177), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (8): Golgi membrane (GO:0000139), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), trans-Golgi network membrane (GO:0032588), protein-containing complex (GO:0032991), Ric1-Rgp1 guanyl-nucleotide exchange factor complex (GO:0034066), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	2
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
Golgi apparatus	2
intercellular transport	1
endosomal transport	1
cytosolic transport	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase binding	1
binding	1
bounding membrane of organelle	1
cytoplasm	1
membrane	1
cell periphery	1
trans-Golgi network	1
organelle membrane	1
cellular_component	1
guanyl-nucleotide exchange factor complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGP1	YBEY	P58557	605
RGP1	C1S	P09871	488
RGP1	POMGNT1	Q8WZA1	393
RGP1	CBX7	O95931	349
RGP1	RIC1	Q4ADV7	349
RGP1	NSD2	O96028	301
RGP1	VPS52	Q8N1B4	287
RGP1	VPS53	Q5VIR6	253
RGP1	RAB6B	Q9NRW1	246
RGP1	RAB6A	P20340	246
RGP1	RAB41	Q5JT25	246
RGP1	RAB6C	Q9H0N0	246
RGP1	TRAPPC5	Q8IUR0	240
RGP1	MGAT1	P26572	224
RGP1	TRAPPC13	A5PLN9	214

IntAct

40 interactions, top by confidence:

A	B	Type	Score
RGP1	RIC1	psi-mi:“MI:0915”(physical association)	0.700
RIC1	RGP1	psi-mi:“MI:0915”(physical association)	0.700
RGP1	RIC1	psi-mi:“MI:0407”(direct interaction)	0.700
RAB33B	RIC1	psi-mi:“MI:0914”(association)	0.590
RAB6A	RIC1	psi-mi:“MI:0914”(association)	0.590
RGP1	RAB6A	psi-mi:“MI:0407”(direct interaction)	0.580
RGP1	RAB6A	psi-mi:“MI:0914”(association)	0.580
	RGP1	psi-mi:“MI:0915”(physical association)	0.560
RGP1		psi-mi:“MI:0915”(physical association)	0.560
RFPL3	RGP1	psi-mi:“MI:0915”(physical association)	0.560
RGP1	tax	psi-mi:“MI:0915”(physical association)	0.560
tax	RGP1	psi-mi:“MI:0915”(physical association)	0.560
SOCS3	RGP1	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
rep	RGP1	psi-mi:“MI:0915”(physical association)	0.490
CCDC102B	TARSL2	psi-mi:“MI:0914”(association)	0.350
GTSF1	MAPK14	psi-mi:“MI:0914”(association)	0.350
SOCS3	PLS1	psi-mi:“MI:0914”(association)	0.350
SYNGR1	TNPO2	psi-mi:“MI:0914”(association)	0.350
ETNK2	ZNF185	psi-mi:“MI:0914”(association)	0.350
C1orf210	SPAG9	psi-mi:“MI:0914”(association)	0.350
CACNG3	NOTCH2	psi-mi:“MI:0914”(association)	0.350
EPHA1	ENC1	psi-mi:“MI:0914”(association)	0.350
OCIAD1	DCTN6	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): NBPF22P (Two-hybrid), RGP1 (Synthetic Lethality), RGP1 (Affinity Capture-MS), RGP1 (Affinity Capture-MS), RGP1 (Affinity Capture-MS), RGP1 (Proximity Label-MS), RFPL3 (Two-hybrid), RGP1 (Proximity Label-MS), RGP1 (Proximity Label-MS), RGP1 (Proximity Label-MS), RGP1 (Proximity Label-MS), RGP1 (Proximity Label-MS), RGP1 (Affinity Capture-RNA), RGP1 (Proximity Label-MS), RGP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

Diamond homologs: Q2T9P3, Q8BHT7, Q92546

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1432 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35750238:CACA:C	acceptor_loss	1.0000
9:35750240:CAG:C	acceptor_loss	1.0000
9:35750241:A:AG	acceptor_gain	1.0000
9:35750241:AGT:A	acceptor_gain	1.0000
9:35750242:G:A	acceptor_loss	1.0000
9:35750242:G:GA	acceptor_gain	1.0000
9:35750242:GT:G	acceptor_gain	1.0000
9:35750242:GTG:G	acceptor_gain	1.0000
9:35750242:GTGA:G	acceptor_gain	1.0000
9:35750377:GAGG:G	donor_loss	1.0000
9:35750378:AGG:A	donor_loss	1.0000
9:35750379:GGTTA:G	donor_loss	1.0000
9:35750380:GTT:G	donor_loss	1.0000
9:35750654:TCAG:T	acceptor_loss	1.0000
9:35750655:CAGG:C	acceptor_loss	1.0000
9:35750656:AGG:A	acceptor_loss	1.0000
9:35751413:G:GG	donor_gain	1.0000
9:35749454:A:T	donor_gain	0.9900
9:35749732:TCTAG:T	acceptor_loss	0.9900
9:35749733:CTAGA:C	acceptor_loss	0.9900
9:35749734:TAGA:T	acceptor_loss	0.9900
9:35749735:A:AG	acceptor_gain	0.9900
9:35749736:G:GG	acceptor_gain	0.9900
9:35749736:G:GT	acceptor_loss	0.9900
9:35749823:T:TA	donor_gain	0.9900
9:35749824:A:AA	donor_gain	0.9900
9:35749870:AG:A	donor_loss	0.9900
9:35749871:GG:G	donor_loss	0.9900
9:35749872:GTGGG:G	donor_loss	0.9900
9:35749873:T:A	donor_loss	0.9900

AlphaMissense

2491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35750256:T:A	W44R	1.000
9:35750256:T:C	W44R	1.000
9:35750258:G:C	W44C	1.000
9:35750258:G:T	W44C	1.000
9:35750266:C:A	A47D	1.000
9:35750259:G:C	A45P	0.999
9:35750260:C:A	A45D	0.999
9:35750262:A:C	S46R	0.999
9:35750264:T:A	S46R	0.999
9:35750264:T:G	S46R	0.999
9:35750269:A:C	Q48P	0.999
9:35750277:T:C	C51R	0.999
9:35750279:C:G	C51W	0.999
9:35750697:T:C	I98T	0.999
9:35750697:T:G	I98S	0.999
9:35750700:T:C	L99P	0.999
9:35750706:G:A	C101Y	0.999
9:35750712:T:C	L103P	0.999
9:35750718:T:A	L105H	0.999
9:35750845:T:G	Y115D	0.999
9:35750897:T:A	V132D	0.999
9:35750902:T:G	Y134D	0.999
9:35750915:T:C	L138P	0.999
9:35750921:T:A	I140N	0.999
9:35750924:G:A	G141D	0.999
9:35751963:T:A	V257D	0.999
9:35752662:T:A	W322R	0.999
9:35752662:T:C	W322R	0.999
9:35749819:T:C	C22R	0.998
9:35749832:T:A	V26D	0.998

dbSNP variants (sampled 300 via entrez): RS1000092662 (9:35763825 T>G), RS1000111753 (9:35764908 G>T), RS1000120959 (9:35778343 C>A,T), RS1000243732 (9:35790519 C>G), RS1000318678 (9:35758183 T>G), RS1000358774 (9:35790121 T>C), RS1000387085 (9:35789473 G>A), RS1000423369 (9:35764261 G>A,T), RS1000528887 (9:35769696 A>T), RS1000586955 (9:35783600 A>G), RS1000690639 (9:35747607 A>C), RS1000699518 (9:35753765 G>A,T), RS1000712043 (9:35783577 T>C), RS1000751991 (9:35753433 G>A), RS1000926582 (9:35778510 C>A)

Disease associations

OMIM: gene MIM:615742 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010703_52	Brain morphology (MOSTest)	1.000000e-08
GCST012227_49	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

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
dicrotophos	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
abrine	increases expression	1
Temozolomide	affects response to substance	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Carmustine	affects response to substance	1
Doxorubicin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Zinc Sulfate	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2J7	HAP1 RGP1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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