RAB3A

Summary

RAB3A (RAB3A, member RAS oncogene family, HGNC:9777) is a protein-coding gene on chromosome 19p13.11, encoding Ras-related protein Rab-3A (P20336). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Enables GTPase activity and myosin V binding activity. Involved in several processes, including acrosomal vesicle exocytosis; plasma membrane repair; and regulation of plasma membrane repair. Located in perinuclear region of cytoplasm.

Source: NCBI Gene 5864 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total — 3 pathogenic
• MANE Select transcript: NM_002866

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9777
Approved symbol	RAB3A
Name	RAB3A, member RAS oncogene family
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105649
Ensembl biotype	protein_coding
OMIM	179490
Entrez	5864

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000222256, ENST00000464076, ENST00000481914, ENST00000515410, ENST00000903464, ENST00000903465, ENST00000920126

RefSeq mRNA: 1 — MANE Select: NM_002866 NM_002866

CCDS: CCDS12372

Canonical transcript exons

ENST00000222256 — 5 exons

Exon	Start	End
ENSE00000690217	18202513	18202740
ENSE00001056333	18196784	18197660
ENSE00001651504	18203896	18204042
ENSE00003459012	18198725	18198849
ENSE00003789848	18200327	18200445

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.0811 / max 1351.8165, expressed in 1512 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179943	24.4147	1453
179942	5.1579	698
179939	0.7600	158
179941	0.5337	147
179938	0.1671	72
179940	0.0478	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	99.06	gold quality
cortical plate	UBERON:0005343	98.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.64	gold quality
cerebellar hemisphere	UBERON:0002245	98.51	gold quality
cerebellar cortex	UBERON:0002129	98.37	gold quality
prefrontal cortex	UBERON:0000451	97.84	gold quality
nucleus accumbens	UBERON:0001882	97.49	gold quality
amygdala	UBERON:0001876	97.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.11	gold quality
cerebellum	UBERON:0002037	97.04	gold quality
putamen	UBERON:0001874	97.00	gold quality
hypothalamus	UBERON:0001898	96.94	gold quality
cingulate cortex	UBERON:0003027	96.59	gold quality
dorsal root ganglion	UBERON:0000044	96.43	gold quality
ventral tegmental area	UBERON:0002691	96.40	gold quality
anterior cingulate cortex	UBERON:0009835	96.36	gold quality
parietal lobe	UBERON:0001872	96.30	gold quality
frontal cortex	UBERON:0001870	96.16	gold quality
frontal lobe	UBERON:0016525	96.12	gold quality
caudate nucleus	UBERON:0001873	95.97	gold quality
ganglionic eminence	UBERON:0004023	95.80	gold quality
neocortex	UBERON:0001950	95.75	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.73	gold quality
postcentral gyrus	UBERON:0002581	95.72	gold quality
telencephalon	UBERON:0001893	95.62	gold quality
cerebral cortex	UBERON:0000956	95.52	gold quality
temporal lobe	UBERON:0001871	95.49	gold quality
brain	UBERON:0000955	95.39	gold quality
pons	UBERON:0000988	95.30	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	263.03
E-GEOD-93593	yes	231.31
E-HCAD-5	yes	50.11
E-HCAD-25	yes	36.20
E-MTAB-7316	yes	16.13
E-ANND-3	no	1.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): F2R, F2RL1, NR1I2

miRNA regulators (miRDB)

51 targeting RAB3A, 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-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4318	99.38	66.94	1505

Literature-anchored findings (GeneRIF, showing 19)

• a possible role in glomerulopathies (PMID:12937130)
• Mutation screening of the RAB3A gene in 47 individuals with autism provided no evidence that DNA variants in this gene are associated with autism. (PMID:15005721)
• Cholesterol content regulates acrosomal exocytosis by enhancing Rab3A plasma membrane association. (PMID:16099449)
• In conclusion, we have found no evidence for RAB3A conferring susceptibility on mental retardation in the Han Chinese population. (PMID:16584842)
• Initiates exocytosis in acrosome when prenylated and activated with guanosine triphosphate (GTP). (PMID:17625073)
• Rab3GEP has a role as the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes (PMID:18559336)
• Epac activates the small G proteins Rap1 and Rab3A to achieve exocytosis (PMID:19546222)
• The maturation of amyloid precursor protein (APP) transport vesicles, including recruitment of conventional kinesin, requires Rab3A GTPase activity. (PMID:19923287)
• Myo5a and Rab3A are direct binding partners and interact on synaptic vesicles and the Myo5a/Rab3A complex is involved in transport of neuronal vesicles (PMID:21349835)
• Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis. (PMID:22753498)
• alpha-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity (PMID:23344955)
• Five compounds which possess good inhibitory activity and may act as potential high affinity inhibitors against Rab3A active site were identified (PMID:24652202)
• Rab3a accelerates cell proliferation by increasing cyclin D1 expression, enhances anti-cancer drug resistance, and increases tumorigenicity and self-renewal of glioma cells. (PMID:24965146)
• Data indicate that exocytic stimuli promote ADP ribosylation factor 6 (ARF6) activation, which accomplishes exocytosis by stimulating Rab3A GTP-Binding Protein. (PMID:25713146)
• Rab3A-22A blocks exocytosis at a stage downstream intra-acrosomal calcium release. (PMID:27613869)
• Rab27/Rabphilin3a/GRAB/Rab3 constitutes a signaling module in sperm exocytosis. (PMID:30599141)
• Unveiling the interaction between the molecular motor Myosin Vc and the small GTPase Rab3A. (PMID:31698103)
• Molecular and functional interactions of alpha-synuclein with Rab3a. (PMID:35809645)
• RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors. (PMID:38512027)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab3ab	ENSDARG00000043835
danio_rerio	rab3aa	ENSDARG00000056347
mus_musculus	Rab3a	ENSMUSG00000031840
rattus_norvegicus	Rab3a	ENSRNOG00000019433

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), 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), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-3A — P20336 (reviewed: P20336)

All UniProt accessions (4): P20336, A0A024R7I7, M0R257, S4R3Q3

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. RAB3A plays a central role in regulated exocytosis and secretion. Controls the recruitment, tethering and docking of secretory vesicles to the plasma membrane. Upon stimulation, switches to its active GTP-bound form, cycles to vesicles and recruits effectors such as RIMS1, RIMS2, Rabphilin-3A/RPH3A, RPH3AL or SYTL4 to help the docking of vesicules onto the plasma membrane. Upon GTP hydrolysis by GTPase-activating protein, dissociates from the vesicle membrane allowing the exocytosis to proceed. Stimulates insulin secretion through interaction with RIMS2 or RPH3AL effectors in pancreatic beta cells. Regulates calcium-dependent lysosome exocytosis and plasma membrane repair (PMR) via the interaction with 2 effectors, SYTL4 and myosin-9/MYH9. Acts as a positive regulator of acrosome content secretion in sperm cells by interacting with RIMS1. Also plays a role in the regulation of dopamine release by interacting with synaptotagmin I/SYT.

Subunit / interactions. Interacts with RIMS1 and RIMS2. Interacts with Rabphilin-3A/RPH3A and Rab effector Noc2/RPH3AL. Interacts with SYTL4. Interacts with RAB3IP. Interacts with SGSM1 and SGSM3. Interacts with SYT1. Interacts with MYH9; this interaction is essential for lysosome exocytosis and plasma membrane repair. Interacts with STXBP1; this interaction promotes RAB3A dissociation from the vesicle membrane. Interacts with SNCA. The GTP-bound form interacts with REP15. Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions. Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction.

Subcellular location. Cytoplasm. Cytosol. Lysosome. Cytoplasmic vesicle. Secretory vesicle. Cell projection. Axon. Cell membrane. Presynapse. Postsynapse.

Tissue specificity. Specifically expressed in brain.

Post-translational modifications. Phosphorylation of Thr-86 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) including RAB3IL1 and MADD which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) including RAB3GAP1 and TBC1D10B which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs) which prevent Rab-GDP dissociation.

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.

RefSeq proteins (1): NP_002857* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR037872	Rab3	Family
IPR050305	Small_GTPase_Rab	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (36 total): binding site 20, modified residue 4, mutagenesis site 4, short sequence motif 2, lipid moiety-binding region 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20336-F1	84.11	0.63

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): 36; 37; 48; 49; 53; 54; 54; 77; 80; 135; 136; 138 …

Post-translational modifications (6): 86, 188, 190, 220, 218, 220

Mutagenesis-validated functional residues (4):

Position	Phenotype
61	no change in rep15 binding affinity.
84	decreased rep15 binding affinity.
86	loss of phosphorylation.
86	phosphomimetic mutant. loss of gdi1, gdi2, chm and chml binding.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-6798695	Neutrophil degranulation
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-888590	GABA synthesis, release, reuptake and degradation
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea

MSigDB gene sets: 312 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_VESICLE_LOCALIZATION, RORA1_01, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_VESICLE_ORGANIZATION, GCANCTGNY_MYOD_Q6, GOBP_INSULIN_SECRETION, GOBP_MEMBRANE_FUSION

GO Biological Process (33): plasma membrane repair (GO:0001778), respiratory system process (GO:0003016), exocytosis (GO:0006887), mitochondrion organization (GO:0007005), neuromuscular synaptic transmission (GO:0007274), axonogenesis (GO:0007409), post-embryonic development (GO:0009791), synaptic vesicle exocytosis (GO:0016079), synaptic vesicle maturation (GO:0016188), insulin secretion (GO:0030073), lung development (GO:0030324), regulation of synaptic vesicle fusion to presynaptic active zone membrane (GO:0031630), lysosome localization (GO:0032418), synaptic vesicle recycling (GO:0036465), constitutive secretory pathway (GO:0045054), regulated exocytosis (GO:0045055), positive regulation of exocytosis (GO:0045921), regulation of short-term neuronal synaptic plasticity (GO:0048172), synaptic vesicle transport (GO:0048489), maintenance of presynaptic active zone structure (GO:0048790), sensory perception of touch (GO:0050975), response to electrical stimulus (GO:0051602), acrosomal vesicle exocytosis (GO:0060478), evoked neurotransmitter secretion (GO:0061670), synaptic vesicle clustering (GO:0097091), regulation of presynaptic dense core granule exocytosis (GO:0099161), positive regulation of regulated secretory pathway (GO:1903307), regulation of plasma membrane repair (GO:1905684), intracellular protein transport (GO:0006886), protein transport (GO:0015031), calcium-ion regulated exocytosis (GO:0017156), regulation of exocytosis (GO:0017157), establishment of localization in cell (GO:0051649)

GO Molecular Function (10): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), protein-macromolecule adaptor activity (GO:0030674), GTP-dependent protein binding (GO:0030742), myosin V binding (GO:0031489), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (26): acrosomal vesicle (GO:0001669), lysosome (GO:0005764), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), axon (GO:0030424), secretory granule membrane (GO:0030667), synaptic vesicle membrane (GO:0030672), terminal bouton (GO:0043195), perinuclear region of cytoplasm (GO:0048471), presynaptic active zone (GO:0048786), clathrin-sculpted acetylcholine transport vesicle membrane (GO:0060201), clathrin-sculpted glutamate transport vesicle membrane (GO:0060203), clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane (GO:0061202), clathrin-sculpted monoamine transport vesicle membrane (GO:0070083), presynapse (GO:0098793), postsynapse (GO:0098794), extracellular vesicle (GO:1903561), cytoplasm (GO:0005737), membrane (GO:0016020), transport vesicle (GO:0030133), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Neurotransmitter release cycle	6
Innate Immune System	1
Post-translational protein modification	1
Rab regulation of trafficking	1
Sensory processing of sound	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
presynapse	4
clathrin-coated vesicle membrane	4
exocytosis	3
transport vesicle membrane	3
establishment of localization in cell	2
synaptic vesicle cycle	2
transport	2
protein binding	2
secretory granule	2
cytoplasm	2
synapse	2
plasma membrane organization	1
wound healing	1
system process	1
respiratory gaseous exchange by respiratory system	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
organelle organization	1
chemical synaptic transmission	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
multicellular organism development	1
multicellular organismal process	1
neurotransmitter secretion	1
regulated exocytosis	1
vesicle-mediated transport in synapse	1
signal release from synapse	1
vesicle organization	1
developmental maturation	1
protein secretion	1
peptide hormone secretion	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
regulation of vesicle fusion	1
synaptic vesicle fusion to presynaptic active zone membrane	1
regulation of synaptic vesicle membrane organization	1

Protein interactions and networks

STRING

2006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB3A	RPH3A	Q9Y2J0	999
RAB3A	RIMS1	Q86UR5	970
RAB3A	RIMS2	Q9UQ26	925
RAB3A	SYP	P08247	922
RAB3A	RPH3AL	Q9UNE2	895
RAB3A	RAB3GAP1	Q15042	884
RAB3A	VAMP2	P19065	881
RAB3A	UNC13B	O14795	857
RAB3A	SYT1	P21579	853
RAB3A	UNC13A	Q9UPW8	853
RAB3A	RAB3IP	Q96QF0	823
RAB3A	SYN1	P17600	817
RAB3A	GDI1	P31150	801
RAB3A	STXBP1	P61764	801
RAB3A	WDR7	Q9Y4E6	791

IntAct

87 interactions, top by confidence:

A	B	Type	Score
RABIF	RAB3A	psi-mi:“MI:0915”(physical association)	0.780
RAB3A	RABIF	psi-mi:“MI:0915”(physical association)	0.780
RABIF	RAB3A	psi-mi:“MI:0914”(association)	0.780
RAB3A	RAB3IP	psi-mi:“MI:0915”(physical association)	0.560
RAB3IP	RAB3A	psi-mi:“MI:0915”(physical association)	0.560
RAB3A	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
RAB3A	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
RAB3A	VRTN	psi-mi:“MI:0915”(physical association)	0.560
EGFR	RAB3A	psi-mi:“MI:0915”(physical association)	0.550
RAB3A	EGFR	psi-mi:“MI:0915”(physical association)	0.550
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
RAB3A	RAB3B	psi-mi:“MI:0914”(association)	0.530
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
RAB3A	CHM	psi-mi:“MI:0914”(association)	0.530
RAB3A	OCRL	psi-mi:“MI:0407”(direct interaction)	0.440
RAB3A	RPH3A	psi-mi:“MI:0915”(physical association)	0.370
RAB3A	CHRM4	psi-mi:“MI:0915”(physical association)	0.370
MAST1	RAB3A	psi-mi:“MI:0915”(physical association)	0.370
PSEN1	RAB3A	psi-mi:“MI:0915”(physical association)	0.370
ANG	DDX39A	psi-mi:“MI:0914”(association)	0.350
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.350

BioGRID (126): RABIF (Two-hybrid), RAB3IP (Two-hybrid), CHML (Affinity Capture-MS), CHM (Affinity Capture-MS), SYTL4 (Affinity Capture-MS), RAB3B (Affinity Capture-MS), MOCOS (Affinity Capture-MS), RAB33B (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), VWA5B2 (Affinity Capture-MS), RANGRF (Affinity Capture-MS), IBA57 (Affinity Capture-MS), WDR45B (Affinity Capture-MS), RAB3A (Affinity Capture-MS), RAB3A (Affinity Capture-MS)

ESM2 similar proteins: C8VQY7, G4MYS1, H9BW96, I1RMF2, O01803, O04157, O24461, O76742, O94655, O97572, P09527, P11023, P18067, P19892, P20336, P24408, P28187, P31022, P32939, P36411, P36864, P51149, P51150, P51151, P63011, P63012, P93267, Q06AU3, Q39573, Q3T0F5, Q40787, Q41640, Q43463, Q4R4R9, Q5R4W9, Q5R9Y4, Q8BHH2, Q948K8, Q99P75, Q9C2L8

Diamond homologs: A4FV54, C4YL11, F1PTE3, O24466, O42819, O76173, O95716, P01123, P07560, P0CY30, P0CY31, P10536, P10949, P11023, P11620, P16976, P17609, P20336, P20790, P20791, P22125, P22127, P22128, P24409, P25228, P28186, P28188, P31584, P33723, P34139, P34140, P35276, P35280, P35281, P35286, P35289, P36861, P40392, P41924, P51153

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
F2RL1	“up-regulates quantity by expression”	RAB3A	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	RAB3A	“transcriptional regulation”
RAB3A	up-regulates	Dense-core_vesicle_exocytosis
RIMS2	“up-regulates activity”	RAB3A	relocalization
RIMS3	“up-regulates activity”	RAB3A	relocalization
RIMS1	“up-regulates activity”	RAB3A	relocalization
RABGGTA	“up-regulates activity”	RAB3A	lipidation
RABGGTB	“up-regulates activity”	RAB3A	lipidation
SYN1	“up-regulates activity”	RAB3A	binding
MADD	“up-regulates activity”	RAB3A	“guanine nucleotide exchange factor”
RAB3GAP1	“down-regulates activity”	RAB3A	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
RAB GEFs exchange GTP for GDP on RABs	6	12.0×	1e-03
Neutrophil degranulation	11	4.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	12	6.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	17
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3359236	NM_002866.5(RAB3A):c.247C>T (p.Arg83Trp)	Pathogenic
4814022	R83W	Pathogenic
4814023	I27T	Pathogenic

SpliceAI

492 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18197656:GAACC:G	acceptor_gain	1.0000
19:18197657:AACC:A	acceptor_gain	1.0000
19:18197658:ACC:A	acceptor_gain	1.0000
19:18197659:CC:C	acceptor_gain	1.0000
19:18197659:CCC:C	acceptor_gain	1.0000
19:18197660:CC:C	acceptor_gain	1.0000
19:18197661:C:CC	acceptor_gain	1.0000
19:18197661:C:T	acceptor_gain	1.0000
19:18197663:G:C	acceptor_gain	1.0000
19:18197668:C:CT	acceptor_gain	1.0000
19:18197669:A:T	acceptor_gain	1.0000
19:18198718:CACT:C	donor_loss	1.0000
19:18198719:ACTC:A	donor_loss	1.0000
19:18198720:CTCA:C	donor_loss	1.0000
19:18198721:TCA:T	donor_loss	1.0000
19:18198722:CAC:C	donor_loss	1.0000
19:18198723:A:AC	donor_gain	1.0000
19:18198724:C:A	donor_loss	1.0000
19:18198724:C:CC	donor_gain	1.0000
19:18198850:C:CC	acceptor_gain	1.0000
19:18198850:C:CG	acceptor_loss	1.0000
19:18200325:A:AC	donor_gain	1.0000
19:18200325:AC:A	donor_gain	1.0000
19:18200326:C:CG	donor_gain	1.0000
19:18200326:CC:C	donor_gain	1.0000
19:18200326:CCA:C	donor_gain	1.0000
19:18200326:CCAG:C	donor_gain	1.0000
19:18200326:CCAGT:C	donor_gain	1.0000
19:18200441:GTGTC:G	acceptor_gain	1.0000
19:18200442:TGTC:T	acceptor_gain	1.0000

AlphaMissense

1466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18198789:C:A	K136N	1.000
19:18198789:C:G	K136N	1.000
19:18198791:T:C	K136E	1.000
19:18200328:A:G	W116R	1.000
19:18200328:A:T	W116R	1.000
19:18200384:C:T	G97D	1.000
19:18200385:C:G	G97R	1.000
19:18200400:A:C	Y92D	1.000
19:18200414:A:T	I87N	1.000
19:18200420:C:G	R85P	1.000
19:18200435:C:A	G80V	1.000
19:18200435:C:T	G80E	1.000
19:18200436:C:A	G80W	1.000
19:18200436:C:G	G80R	1.000
19:18200436:C:T	G80R	1.000
19:18200443:G:C	D77E	1.000
19:18200443:G:T	D77E	1.000
19:18200444:T:A	D77V	1.000
19:18200444:T:C	D77G	1.000
19:18200444:T:G	D77A	1.000
19:18200445:C:A	D77Y	1.000
19:18200445:C:G	D77H	1.000
19:18202513:C:A	W76C	1.000
19:18202513:C:G	W76C	1.000
19:18202515:A:G	W76R	1.000
19:18202515:A:T	W76R	1.000
19:18202523:A:G	L73P	1.000
19:18202564:G:C	F59L	1.000
19:18202564:G:T	F59L	1.000
19:18202566:A:G	F59L	1.000

dbSNP variants (sampled 300 via entrez): RS1000267232 (19:18201800 G>T), RS1000344399 (19:18201728 C>T), RS1000599656 (19:18200150 G>C,T), RS1001180638 (19:18202146 T>C), RS1001621223 (19:18196433 A>C), RS1001633094 (19:18202430 A>T), RS1001815151 (19:18201386 A>G), RS1002152565 (19:18199787 G>A), RS1002367915 (19:18206041 T>C), RS1002591870 (19:18200553 G>T), RS1003181401 (19:18198969 A>C,T), RS1003258949 (19:18203739 C>A), RS1003344473 (19:18197617 G>A), RS1003591834 (19:18204515 G>T), RS1003642893 (19:18204841 A>G)

Disease associations

OMIM: gene MIM:179490 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008476_24	Emphysema annual change measurement in smokers (percent low attenuation area)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression, affects expression	3
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
mitomycin C-DNA adduct	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
(+)-JQ1 compound	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Estradiol	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Niclosamide	increases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1
Butyric Acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7FQ	Abcam SK-N-FI RAB3A KO	Cancer cell line	Male
CVCL_TI16	HAP1 RAB3A (-) 1	Cancer cell line	Male
CVCL_TI17	HAP1 RAB3A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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