RAB6A

Summary

RAB6A (RAB6A, member RAS oncogene family, HGNC:9786) is a protein-coding gene on chromosome 11q13.4, encoding Ras-related protein Rab-6A (P20340). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. It is a selective cancer dependency (DepMap: 48.8% of cell lines).

This gene encodes a member of the RAB family, which belongs to the small GTPase superfamily. GTPases of the RAB family bind to various effectors to regulate the targeting and fusion of transport carriers to acceptor compartments. This protein is located at the Golgi apparatus, which regulates trafficking in both a retrograde (from early endosomes and Golgi to the endoplasmic reticulum) and an anterograde (from the Golgi to the plasma membrane) directions. Myosin II is an effector of this protein in these processes. This protein is also involved in assembly of human cytomegalovirus (HCMV) by interacting with the cellular protein Bicaudal D1, which interacts with the HCMV virion tegument protein, pp150. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 5870 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 20 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 48.8% of screened cell lines
• MANE Select transcript: NM_198896

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9786
Approved symbol	RAB6A
Name	RAB6A, member RAS oncogene family
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175582
Ensembl biotype	protein_coding
OMIM	179513
Entrez	5870

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000310653, ENST00000336083, ENST00000400470, ENST00000536566, ENST00000537446, ENST00000540771, ENST00000541588, ENST00000541795, ENST00000541973, ENST00000545625, ENST00000851637, ENST00000851638, ENST00000919626, ENST00000919627

RefSeq mRNA: 4 — MANE Select: NM_198896 NM_001243718, NM_001243719, NM_002869, NM_198896

CCDS: CCDS58155, CCDS58156, CCDS8223, CCDS8224

Canonical transcript exons

ENST00000336083 — 8 exons

Exon	Start	End
ENSE00001184543	73718613	73718718
ENSE00001358753	73679654	73679720
ENSE00001759909	73720846	73720899
ENSE00002238736	73760566	73761074
ENSE00002297551	73675638	73677962
ENSE00003467266	73716251	73716362
ENSE00003622686	73730765	73730823
ENSE00003629629	73707420	73707513

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3626 / max 326.8838, expressed in 1820 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121269	41.5648	1818
121266	1.6228	950
121268	1.0014	583
121267	0.9507	661
121263	0.7070	346
121265	0.5510	258
121262	0.5262	250
121264	0.4386	155

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.88	gold quality
calcaneal tendon	UBERON:0003701	98.80	gold quality
anterior cingulate cortex	UBERON:0009835	97.95	gold quality
ganglionic eminence	UBERON:0004023	97.88	gold quality
cingulate cortex	UBERON:0003027	97.87	gold quality
ventricular zone	UBERON:0003053	97.86	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.79	gold quality
colonic epithelium	UBERON:0000397	97.78	gold quality
frontal pole	UBERON:0002795	97.72	gold quality
prefrontal cortex	UBERON:0000451	97.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.45	gold quality
right frontal lobe	UBERON:0002810	97.41	gold quality
adrenal tissue	UBERON:0018303	97.38	gold quality
stromal cell of endometrium	CL:0002255	97.20	gold quality
middle frontal gyrus	UBERON:0002702	97.10	gold quality
rectum	UBERON:0001052	97.02	gold quality
popliteal artery	UBERON:0002250	96.96	gold quality
tibial artery	UBERON:0007610	96.96	gold quality
right coronary artery	UBERON:0001625	96.73	gold quality
descending thoracic aorta	UBERON:0002345	96.71	gold quality
cerebellar hemisphere	UBERON:0002245	96.68	gold quality
cerebellar cortex	UBERON:0002129	96.66	gold quality
monocyte	CL:0000576	96.65	gold quality
aorta	UBERON:0000947	96.64	gold quality
thoracic aorta	UBERON:0001515	96.53	gold quality
ascending aorta	UBERON:0001496	96.50	gold quality
artery	UBERON:0001637	96.49	gold quality
islet of Langerhans	UBERON:0000006	96.43	gold quality
tendon	UBERON:0000043	96.39	gold quality
lower esophagus mucosa	UBERON:0035834	96.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	no	3.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting RAB6A, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4713-5P	99.78	67.80	1794

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 48.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 38)

• recombinant antibodies specific to the GTP-bound conformation of Rab6 were generated and used to locate Rab6; Rab6 was in its GTP-bound conformation on the Golgi apparatus and transport intermediates (PMID:12738866)
• Rab6A and Rab6A’ regulate microtubule-dependent recycling at the trans-Golgi network (PMID:15483056)
• 10 genes were down-regulated following treatment of the T-ALL cells with 0.15 and 1.5 microg/mL of metal ores at 72 h. GTP binding activity, RaB small monomeric GTPase activity, protein transporter activity. (PMID:15747776)
• Results show the crystal structure of the GTPase Rab6A in the GTP bound form. (PMID:16332443)
• Rab6A’ likely regulates the dynamics of the dynein/dynactin complex at the kinetochores and consequently the inactivation of the Mad2-spindle checkpoint. (PMID:16395330)
• Results show that Rab6A and Rab6A’ perform different functions within the cell and suggests a novel role for Rab6A’ as the major Rab6 isoform regulating previously described Rab6-dependent transport pathways. (PMID:16536738)
• role of the Rab6 isoforms in retrograde transport of ricin using both oligo- and vector-based RNAi assays (PMID:16683916)
• a highly significant correlation between the Rab6 and the UPR marker BiP in Alzheimer disease brains. (PMID:17573808)
• These data demonstrate that although Rab6 is not essential for secretion, it controls the organization of exocytosis within the cellular space. (PMID:17681140)
• Rab6 regulates distinct Golgi trafficking pathways involving two separate protein complexes: ZW10/RINT-1 and COG. (PMID:17699596)
• These data demonstrate that Rab2 and Rab6 differentially influence anterograde transport and signaling of GPCRs. (PMID:17716866)
• DYNLRB1 specifically interacts with all three Rab6 isoforms and co-localises at the Golgi. (PMID:18044744)
• Data show that iPLA(1)gamma is a novel membrane transport factor that contributes to a specific Golgi-to-ER retrograde pathway distinct from presently characterized COPI- and Rab6-dependent pathways. (PMID:19632984)
• Study demonstrates that Golgi recruitment of endogenous GCC185 does not involve Rab6A/A’ and Arl1. (PMID:19703403)
• Data show that Rab6, a Golgi-associated Rab, forms a complex with myosin II, contributes to its localization at the Golgi complex and, unexpectedly, controls the fission of Rab6 vesicles. (PMID:20562865)
• The authors found that the small GTPase Rab6 also interacts indirectly with cytomegalovirus pp150 through its interaction with Bicaudal D1. (PMID:21411515)
• In contrast to wild-type R6IP1-Rab6 crystals, which took several weeks to grow to full size, the engineered R6IP1 (RPdel)-Rab6 crystals could be grown in a matter of days (PMID:21543860)
• Rab6 is required for Rab8A association with exocytotic vesicles. (PMID:21596566)
• Rab6 modulates the unfolded protein response (UPR), increased levels inhibit whereas decreased levels augment UPR induction. (PMID:22124028)
• Electron tomography reveals Rab6 is essential to the trafficking of trans-Golgi clathrin and COPI-coated vesicles and the maintenance of Golgi cisternal number (PMID:22335553)
• GTP-bound form of Rab6 promotes retrograde trafficking of cav-2 from the Golgi to ER (PMID:22607032)
• the crystal structure of the human Rab6A’(Q72L) mutant form at 1.9A resolution is reported. (PMID:22750005)
• 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)
• The presence of an active pool of Rab6 within host cells early during infection is required to support efficient intracellular growth of L. pneumophila. (PMID:23569112)
• Mint1 826 bridges APP to the small GTPase (PMID:23737971)
• Data indicate that myosin Va interacted with multiple new Rab subfamilies including Rab6, Rab14 and Rab39B. (PMID:24006491)
• Data suggest that miR-5100 promotes tumor growth by facilitating the G1/S transition and targeting Rab6. (PMID:25754817)
• Rab6A binding to KIF1C’s motor domain represents an entirely new mode of regulation for a kinesin motor, and likely has important consequences for KIF1C’s cellular functions. (PMID:25821985)
• several analyses of vesicular transport demonstrated that Rab6A and BICD2 play crucial roles in Golgi tubule fusion with the endoplasmic reticulum (ER) in brefeldin A (BFA)-treated cells (PMID:25962623)
• GORAB missense mutation disrupt RAB6 protein binding in genetic skin diseases. (PMID:26000619)
• Ectopic expression of an N-terminal-truncated ARHGEF10 mutant led to the generation of large vesicle-like structures containing both Rab6 and Rab8. (PMID:27550519)
• it was suggested that ARHGEF10 is involved in the regulation of Rab6A and Rab8A localization and invasion of breast carcinoma cells, in which Rab8 also acts via regulation of membrane trafficking. (PMID:28448737)
• These results suggest that miR-5100 increases the cisplatin resistance of the lung cancer stem cells by inhibiting the Rab6. (PMID:29144562)
• LAT, once internalized, transits through the Golgi-trans-Golgi network (TGN), where it is repolarized to the immune synapse. (PMID:29440364)
• We observed that, irrespective of the transported cargos, most post-Golgi carriers are positive for RAB6 and that its inactivation leads to a broad reduction of protein secretion. RAB6 may thus be a general regulator of post-Golgi secretion. (PMID:31142554)
• Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis. (PMID:33012781)
• Rab6 regulates recycling and retrograde trafficking of MR1 molecules. (PMID:33247182)
• RAB6A functions as a critical modulator of the stem-like subsets in cholangiocarcinoma. (PMID:37278569)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab6a	ENSDARG00000103714
mus_musculus	Rab6a	ENSMUSG00000030704
rattus_norvegicus	Rab6a	ENSRNOG00000018176
drosophila_melanogaster	Rab6	FBGN0015797
caenorhabditis_elegans		WBGENE00004269

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955)

Protein

Protein identifiers

Ras-related protein Rab-6A — P20340 (reviewed: P20340)

All UniProt accessions (4): P20340, A0A024R5J5, F5GX61, F5H3K7

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB6A acts as a regulator of COPI-independent retrograde transport from the Golgi apparatus towards the endoplasmic reticulum (ER). Has a low GTPase activity. Recruits VPS13B to the Golgi membrane. Plays a role in neuron projection development.

Subunit / interactions. Interacts (GTP-bound) with DYNLRB1; the interaction is direct. Interacts with BICD1. Interacts with BICD2; the interaction is direct. Interacts (GTP-bound) with VPS13B. Interacts with BICD1. Interacts (GDP-bound) with DYNLRB1; the interaction is direct. Interacts (GTP-bound) with VPS13B. Interacts with BICDL1; leads to its accumulation in the pericentrosomal region. Interacts with SCYL1BP1. Interacts with VSP52. Interacts with RABGAP1. Interacts with GCC2 (via its GRIP domain). Interacts with RAB6IP1 (via its RUN 1 domain). Interacts with TMF1. Interacts with CIMAP3. Interacts (GTP-bound) with APBA1/MINT1 isoform 2, also called Mint1_826, but not with isoform 1. Interacts with RIC1; the interaction is direct with a preference for RAB6A-GDP. Interacts with RGP1; the interaction is direct with a preference for RAB6A-GDP. (Microbial infection) Interacts with human cytomegalovirus protein UL32.

Subcellular location. Golgi apparatus membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane Golgi apparatus membrane Golgi apparatus membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Prenylated.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).

Domain organisation. Switch 1, switch 2 and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drives interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

Similarity. Belongs to the small GTPase superfamily. Rab family.

Isoforms (4)

UniProt ID	Names	Canonical?
P20340-1	1, Rab-6a	yes
P20340-2	2, Rab-6a’, Rab-6C, Rab6C
P20340-3	3
P20340-4	4

RefSeq proteins (4): NP_001230647, NP_001230648, NP_002860, NP_942599* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050227	Rab	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (53 total): binding site 20, helix 9, strand 6, modified residue 4, splice variant 3, mutagenesis site 3, short sequence motif 2, lipid moiety-binding region 2, initiator methionine 1, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1YZQ	X-RAY DIFFRACTION	1.78
2GIL	X-RAY DIFFRACTION	1.82
4DKX	X-RAY DIFFRACTION	1.9
5LEF	X-RAY DIFFRACTION	2.09
3BBP	X-RAY DIFFRACTION	3
3CWZ	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20340-F1	85.76	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 28; 39; 40; 42; 45; 45; 68; 71; 126; 127; 129; 156 …

Post-translational modifications (6): 2, 82, 184, 208, 206, 208

Mutagenesis-validated functional residues (3):

Position	Phenotype
27	loss of apba1-binding. no loss of ric1- and rgp1-binding.
46	loss of rab6ip1-binding.
72	loss of gtpase activity. interacts with apba1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1912420	Pre-NOTCH Processing in Golgi
R-HSA-6798695	Neutrophil degranulation
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8854214	TBC/RABGAPs
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 269 (showing top): MORF_MTA1, REACTOME_SIGNALING_BY_NOTCH, REACTOME_INNATE_IMMUNE_SYSTEM, CCAWYNNGAAR_UNKNOWN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6, DITTMER_PTHLH_TARGETS_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS, CREBP1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE

GO Biological Process (13): intracellular protein transport (GO:0006886), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), intra-Golgi vesicle-mediated transport (GO:0006891), peptidyl-cysteine methylation (GO:0018125), antigen processing and presentation (GO:0019882), neuron projection development (GO:0031175), protein localization to Golgi apparatus (GO:0034067), early endosome to Golgi transport (GO:0034498), retrograde transport, endosome to Golgi (GO:0042147), minus-end-directed organelle transport along microtubule (GO:0072385), protein localization to Golgi membrane (GO:1903292), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), protein domain specific binding (GO:0019904), myosin V binding (GO:0031489), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (16): Golgi membrane (GO:0000139), acrosomal membrane (GO:0002080), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), secretory granule membrane (GO:0030667), cytoplasmic vesicle (GO:0031410), trans-Golgi network membrane (GO:0032588), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062), endosome to plasma membrane transport vesicle (GO:0070381)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Rab regulation of trafficking	2
Pre-NOTCH Expression and Processing	1
Innate Immune System	1
Golgi-to-ER retrograde transport	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
Golgi vesicle transport	3
cytoplasm	3
intracellular protein localization	2
transport	2
bounding membrane of organelle	2
organelle membrane	2
protein transport	1
intracellular transport	1
protein methylation	1
peptidyl-cysteine modification	1
immune system process	1
neuron development	1
plasma membrane bounded cell projection organization	1
protein localization to organelle	1
retrograde transport, endosome to Golgi	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
organelle transport along microtubule	1
protein localization to Golgi apparatus	1
protein localization to membrane	1
establishment of protein localization	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
myosin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
acrosomal vesicle	1
secretory granule membrane	1
nuclear lumen	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

2208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB6A	KIF20A	O95235	992
RAB6A	GCC2	Q8IWJ2	991
RAB6A	DENND5A	Q6IQ26	986
RAB6A	GORAB	Q5T7V8	975
RAB6A	ERC1	Q8IUD2	964
RAB6A	BICD2	Q8TD16	944
RAB6A	BICD1	Q96G01	933
RAB6A	BICDL1	Q6ZP65	887
RAB6A	VPS53	Q5VIR6	855
RAB6A	TMF1	P82094	846
RAB6A	RAB8A	P24407	824
RAB6A	KIF1C	O43896	789
RAB6A	VPS13B	Q7Z7G8	785
RAB6A	GOLPH3	Q9H4A6	761
RAB6A	TBC1D15	Q8TC07	756

IntAct

132 interactions, top by confidence:

A	B	Type	Score
OCRL	RAB6A	psi-mi:“MI:0407”(direct interaction)	0.870
RAB6A	OCRL	psi-mi:“MI:0915”(physical association)	0.870
OCRL	RAB6A	psi-mi:“MI:0915”(physical association)	0.870
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PMM1	RAB6A	psi-mi:“MI:0915”(physical association)	0.670
RAB6A	PMM1	psi-mi:“MI:0915”(physical association)	0.670
OCRL	AP2A1	psi-mi:“MI:0914”(association)	0.640
GCC2	RAB6A	psi-mi:“MI:0407”(direct interaction)	0.620
RAB6A	GCC2	psi-mi:“MI:0407”(direct interaction)	0.620
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
RAB6A	RIC1	psi-mi:“MI:0407”(direct interaction)	0.590
RAB6A	RIC1	psi-mi:“MI:0914”(association)	0.590
RAB6A	RIC1	psi-mi:“MI:0915”(physical association)	0.590
RGP1	RAB6A	psi-mi:“MI:0407”(direct interaction)	0.580
RGP1	RAB6A	psi-mi:“MI:0914”(association)	0.580
Bicdl1	KIF1C	psi-mi:“MI:0403”(colocalization)	0.540

BioGRID (216): RAB6A (Two-hybrid), BICD1 (Two-hybrid), BICD2 (Two-hybrid), RAB6A (Two-hybrid), RAB6A (Two-hybrid), DCTN1 (Two-hybrid), BICD1 (Reconstituted Complex), KIF20A (Reconstituted Complex), RAB6A (Reconstituted Complex), RAB6A (Affinity Capture-Western), RAB6A (Affinity Capture-MS), RAB6A (Affinity Capture-MS), RAB6A (Affinity Capture-MS), RAB6A (Affinity Capture-MS), RAB6A (Affinity Capture-MS)

ESM2 similar proteins: A6QR46, C4YL11, O00194, O18334, O23657, O49841, O80501, P0CY30, P0CY31, P10949, P17608, P20340, P34213, P35279, P35289, P35293, P36017, P55745, P59190, P61294, P62823, P62824, P90726, Q05976, Q0IIG8, Q17R06, Q1KME6, Q1RMR4, Q22782, Q54DA7, Q55FK2, Q5R5H5, Q5RAV6, Q5ZLG1, Q6DHC1, Q8CG50, Q8HZJ5, Q8K386, Q8MXS1, Q96E17

Diamond homologs: A4FV54, A6QR46, M0RC99, O18333, O18334, O80501, P05712, P11023, P16976, P17608, P18066, P20336, P20339, P20340, P22127, P22128, P24409, P25228, P29687, P31582, P31583, P34213, P35276, P35278, P35279, P35280, P35292, P36017, P36586, P36863, P49103, P49104, P51147, P51148, P53994, P55258, P61006, P61007, P61019, P61020

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
RAB6A	“down-regulates activity”	VPS13B	binding
RAB6A	“up-regulates activity”	VPS13B	binding
RAB6A	up-regulates	Neurite_outgrowth
KIF1C	“up-regulates quantity”	RAB6A	relocalization
RAB6A	up-regulates	Synaptic_vesicle_exocytosis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
NCAM signaling for neurite out-growth	5	12.6×	2e-03
Retrograde transport at the Trans-Golgi-Network	6	12.2×	8e-04
TBC/RABGAPs	5	12.0×	2e-03
Regulation of RAS by GAPs	6	10.8×	1e-03
RAB GEFs exchange GTP for GDP on RABs	9	10.3×	1e-04
RAB geranylgeranylation	6	9.6×	1e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	7.1×	9e-03
Anchoring of the basal body to the plasma membrane	6	6.3×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of long-term neuronal synaptic plasticity	6	49.2×	2e-06
peptidyl-tyrosine phosphorylation	5	17.4×	3e-03
Ras protein signal transduction	7	11.9×	7e-04
retrograde transport, endosome to Golgi	6	10.2×	5e-03
endocytosis	8	6.3×	6e-03
protein transport	12	4.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1761 predictions. Top by Δscore:

Variant	Effect	Δscore
11:73677960:TCA:T	acceptor_gain	1.0000
11:73677961:CA:C	acceptor_gain	1.0000
11:73677961:CAC:C	acceptor_gain	1.0000
11:73677963:C:CC	acceptor_gain	1.0000
11:73679653:CTAT:C	donor_gain	1.0000
11:73679721:C:CC	acceptor_gain	1.0000
11:73707417:TACC:T	donor_loss	1.0000
11:73707418:A:AT	donor_loss	1.0000
11:73707419:CCTG:C	donor_gain	1.0000
11:73707509:CTTGC:C	acceptor_gain	1.0000
11:73707510:TTGC:T	acceptor_gain	1.0000
11:73707511:TGC:T	acceptor_gain	1.0000
11:73707512:GC:G	acceptor_gain	1.0000
11:73707512:GCC:G	acceptor_loss	1.0000
11:73707513:CC:C	acceptor_gain	1.0000
11:73707513:CCTG:C	acceptor_loss	1.0000
11:73707514:C:CC	acceptor_gain	1.0000
11:73707515:T:A	acceptor_loss	1.0000
11:73716245:CCATA:C	donor_loss	1.0000
11:73716246:CATA:C	donor_loss	1.0000
11:73716247:ATACC:A	donor_loss	1.0000
11:73716248:TA:T	donor_loss	1.0000
11:73716250:C:A	donor_loss	1.0000
11:73716250:CCT:C	donor_gain	1.0000
11:73720844:A:AC	donor_gain	1.0000
11:73720845:C:CC	donor_gain	1.0000
11:73730760:AATAC:A	donor_loss	1.0000
11:73730761:ATACC:A	donor_loss	1.0000
11:73730762:TA:T	donor_loss	1.0000
11:73730763:A:C	donor_loss	1.0000

AlphaMissense

1374 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:73716271:T:A	K127N	1.000
11:73716271:T:G	K127N	1.000
11:73716272:T:A	K127I	1.000
11:73716273:T:C	K127E	1.000
11:73716274:A:C	N126K	1.000
11:73716274:A:T	N126K	1.000
11:73716278:C:T	G125E	1.000
11:73716279:C:G	G125R	1.000
11:73716279:C:T	G125R	1.000
11:73716320:A:T	V111D	1.000
11:73716331:C:A	W107C	1.000
11:73716331:C:G	W107C	1.000
11:73716333:A:G	W107R	1.000
11:73716333:A:T	W107R	1.000
11:73718621:T:A	D94V	1.000
11:73718630:A:T	V91D	1.000
11:73718633:A:T	V90D	1.000
11:73718636:G:T	A89E	1.000
11:73718645:G:A	S86F	1.000
11:73718651:C:G	R84P	1.000
11:73718654:A:T	I83N	1.000
11:73718669:A:C	L78W	1.000
11:73718669:A:G	L78S	1.000
11:73718677:G:C	F75L	1.000
11:73718677:G:T	F75L	1.000
11:73718678:A:C	F75C	1.000
11:73718678:A:G	F75S	1.000
11:73718679:A:C	F75V	1.000
11:73718679:A:G	F75L	1.000
11:73718679:A:T	F75I	1.000

dbSNP variants (sampled 300 via entrez): RS1000009512 (11:73702383 G>A), RS1000033049 (11:73707139 A>AG), RS1000076706 (11:73747149 A>C), RS1000144318 (11:73744020 C>T), RS1000159740 (11:73712636 C>A), RS1000173553 (11:73721920 T>C), RS1000193739 (11:73712978 A>C,G), RS1000210264 (11:73682016 T>C), RS1000224108 (11:73722462 T>C,G), RS1000288407 (11:73688212 A>C), RS1000292302 (11:73728140 G>T), RS1000311416 (11:73718084 T>A), RS1000356783 (11:73756928 A>C,G), RS1000359911 (11:73688542 A>G), RS1000369160 (11:73679141 G>A,T)

Disease associations

OMIM: gene MIM:179513 | 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
GCST001762_405	Obesity-related traits	4.000000e-06
GCST005760_4	Dimensional psychopathology (Cognitive)	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0009098	cognitive domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105703 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,371 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL415049	BARASERTIB	3	2,371

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 6 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	Kd	33	nM	BARASERTIB
6.27	Kd	534.8	nM	CHEMBL5653589
6.27	ED50	534.8	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 232 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[ethyl-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl]amino]quinazolin-7-yl]oxypropyl]amino]ethyl dihydrogen phosphate	1425150: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0330	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149178: Binding affinity to human RAB6A incubated for 45 mins by Kinobead based pull down assay	kd	0.5348	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	affects expression, increases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, increases expression, affects cotreatment, affects localization	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
dibenzo(a,l)pyrene	increases expression	1
epigallocatechin gallate	increases expression	1
tamibarotene	affects expression	1
2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid	decreases prenylation	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Risedronic Acid	decreases prenylation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991863	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3FP	Abcam HEK293T RAB6A KO	Transformed cell line	Female
CVCL_TI22	HAP1 RAB6A (-) 1	Cancer cell line	Male
CVCL_TI23	HAP1 RAB6A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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